Journal of Translational Autoimmunity最新文献

Leucine enhances the cGAS-STING-NLRP3 pathway in autoimmune thyroiditis

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-03-22 DOI: 10.1016/j.jtauto.2025.100284

Xin Shen , Tingting Feng , Shangbin Li , Xingxin Wang , Wenhui Zhang , Shouyan Wang , Xiaohan Zhang , Jiguo Yang , Yuanxiang Liu

Background

Branched-chain amino acids (BCAAs), including isoleucine (Ile), leucine (Leu), and valine (Val), are substrates for synthesising nitrogenous compounds and signalling molecules involved in regulating immunity. To date, data on the role of BCAAs in autoimmune thyroiditis (AIT) are lacking; therefore, this study aimed to determine the causality using two-sample Mendelian randomisation (MR) and explored the role of BCAAs in the cGAS-STING-NLRP3 pathway in vitro.

Methods

The causal relationship between BCAAs and the pathogenesis of AIT were identified using a two-sample MR study. The anti-inflammatory effects of BCAAs and their role in the cGAS-STING-NLRP3 pathway were investigated in lipopolysaccharide (LPS)- induced thyroid follicular cells (TFCs).

Results

Our findings indicate that BCAAs are a pathogenic factor for AIT (IVW OR = 4.960; 95 % CI = (1.54,15.940); P = 0.007). Leu significantly exacerbated the inflammatory response of thyroid cells, as evidenced by the up-regulation of tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-6 and down-regulation of TGF-β1; simultaneously aggravated cellular injury and oxidative stress; significantly increased the expression of Sestrin2/p-mTOR and cGAS/STING/NLRP3 in AIT cells. Furthermore, the expression of IL-18 and IL-1β was significantly increased. Conversely, Leu deprivation induced cell injury, decreased oxidative stress, and inhibited Sestrin2/p-mTOR and cGAS/STING/NLRP3 pathways.

Conclusion

Our findings suggest a potential causal effect of genetically predicted Leu on AIT; Leu significantly exacerbated the inflammatory response and cellular damage in AIT cells. The mechanism by which Leu induces inflammation involves activating the promoted Sestrin2/mTOR and cGAS-STING-NLRP3 signalling pathways. Our study proposes a novel mechanism for the contributions of Leu in AIT and potential therapeutic strategies involving Leu deprivation in treating AIT.

{"title":"Leucine enhances the cGAS-STING-NLRP3 pathway in autoimmune thyroiditis","authors":"Xin Shen , Tingting Feng , Shangbin Li , Xingxin Wang , Wenhui Zhang , Shouyan Wang , Xiaohan Zhang , Jiguo Yang , Yuanxiang Liu","doi":"10.1016/j.jtauto.2025.100284","DOIUrl":"10.1016/j.jtauto.2025.100284","url":null,"abstract":"<div><h3>Background</h3><div>Branched-chain amino acids (BCAAs), including isoleucine (Ile), leucine (Leu), and valine (Val), are substrates for synthesising nitrogenous compounds and signalling molecules involved in regulating immunity. To date, data on the role of BCAAs in autoimmune thyroiditis (AIT) are lacking; therefore, this study aimed to determine the causality using two-sample Mendelian randomisation (MR) and explored the role of BCAAs in the cGAS-STING-NLRP3 pathway <em>in vitro</em>.</div></div><div><h3>Methods</h3><div>The causal relationship between BCAAs and the pathogenesis of AIT were identified using a two-sample MR study. The anti-inflammatory effects of BCAAs and their role in the cGAS-STING-NLRP3 pathway were investigated in lipopolysaccharide (LPS)- induced thyroid follicular cells (TFCs).</div></div><div><h3>Results</h3><div>Our findings indicate that BCAAs are a pathogenic factor for AIT (IVW OR = 4.960; 95 % CI = (1.54,15.940); <em>P</em> = 0.007). Leu significantly exacerbated the inflammatory response of thyroid cells, as evidenced by the up-regulation of tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-6 and down-regulation of TGF-β1; simultaneously aggravated cellular injury and oxidative stress; significantly increased the expression of Sestrin2/p-mTOR and cGAS/STING/NLRP3 in AIT cells. Furthermore, the expression of IL-18 and IL-1β was significantly increased. Conversely, Leu deprivation induced cell injury, decreased oxidative stress, and inhibited Sestrin2/p-mTOR and cGAS/STING/NLRP3 pathways.</div></div><div><h3>Conclusion</h3><div>Our findings suggest a potential causal effect of genetically predicted Leu on AIT; Leu significantly exacerbated the inflammatory response and cellular damage in AIT cells. The mechanism by which Leu induces inflammation involves activating the promoted Sestrin2/mTOR and cGAS-STING-NLRP3 signalling pathways. Our study proposes a novel mechanism for the contributions of Leu in AIT and potential therapeutic strategies involving Leu deprivation in treating AIT.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100284"},"PeriodicalIF":4.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A placebo-controlled Phase 2 trial of E6011, anti-human fractalkine monoclonal antibody, in primary biliary cholangitis

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-03-20 DOI: 10.1016/j.jtauto.2025.100283

Atsushi Tanaka , Masanori Abe , Tadashi Namisaki , Shinji Shimoda , Mikio Zeniya , Akio Ido , Hitoshi Yoshiji , Hiromasa Ohira , Kenichi Harada , Yuko Kakuda , Atsushi Umeda , Yuki Kamiya , Yukari Higashine , Seiichiro Hojo , Toshio Imai , Tetsu Kawano , Yasuni Nakanuma , Hirohito Tsubouchi

Background

While ursodeoxycholic acid (UDCA) remains the first-line therapy for primary biliary cholangitis (PBC), the autoimmune nature of PBC underscores the need for treatments targeting immunological pathways that may achieve a cure. E6011, a novel humanized anti-fractalkine monoclonal antibody, has emerged as a potential therapeutic option for PBC. We conducted a randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of E6011 in patients with PBC with an incomplete response to UDCA.

Methods

The study was composed of 12-week Double-Blind Phase (placebo, E6011 10 mg/kg/month, 15 mg/kg/month, or 10 mg/kg/every other week [eow]) followed by a 52-week Open-Label Phase. The primary endpoint was the percent change in alkaline phosphatase (ALP) at Week 12.

Results

A total of 29 patients were enrolled. Histological evaluation at screening revealed that 83 % of the enrolled patients were classified as Stage 4 according to the Nakanuma Classification. The mean percent changes in ALP at Week 12 were +0.45 % in the placebo, +0.65 % in the 10 mg/kg/month, +1.23 % in the 15 mg/kg/month and +1.19 % in the 10 mg/kg/eow, with no observed trends toward ALP reduction in the E6011 treatment. Based on the interim analysis, the study was discontinued due to a lack of the efficacy. E6011 was generally safe and well tolerated.

Conclusion

This study of E6011 failed to meet the primary endpoint in patients with PBC with an incomplete response to UDCA. The advanced histological severity present in more than 80 % of patients at baseline may have contributed to these findings.

背景尽管熊去氧胆酸（UDCA）仍是治疗原发性胆汁性胆管炎（PBC）的一线疗法，但 PBC 的自身免疫性质突出表明，需要针对免疫途径的治疗方法来实现治愈。E6011是一种新型人源化抗小动脉粥样硬化单克隆抗体，已成为PBC的潜在治疗方案。我们进行了一项随机、安慰剂对照、双盲研究，以评估 E6011 在对 UDCA 反应不完全的 PBC 患者中的疗效和安全性。主要终点是第12周时碱性磷酸酶（ALP）的变化百分比。筛查时的组织学评估显示，根据中沼分类法，83%的入组患者被划分为4期。第12周时，安慰剂的ALP平均变化率为+0.45%，10 mg/kg/月为+0.65%，15 mg/kg/月为+1.23%，10 mg/kg/ow为+1.19%，E6011治疗未观察到ALP下降趋势。根据中期分析，该研究因缺乏疗效而终止。E6011总体上安全且耐受性良好。结论这项E6011研究未能在对UDCA反应不完全的PBC患者中达到主要终点。80%以上的患者在基线时组织学严重程度已达到晚期，这可能是导致上述结果的原因之一。

{"title":"A placebo-controlled Phase 2 trial of E6011, anti-human fractalkine monoclonal antibody, in primary biliary cholangitis","authors":"Atsushi Tanaka , Masanori Abe , Tadashi Namisaki , Shinji Shimoda , Mikio Zeniya , Akio Ido , Hitoshi Yoshiji , Hiromasa Ohira , Kenichi Harada , Yuko Kakuda , Atsushi Umeda , Yuki Kamiya , Yukari Higashine , Seiichiro Hojo , Toshio Imai , Tetsu Kawano , Yasuni Nakanuma , Hirohito Tsubouchi","doi":"10.1016/j.jtauto.2025.100283","DOIUrl":"10.1016/j.jtauto.2025.100283","url":null,"abstract":"<div><h3>Background</h3><div>While ursodeoxycholic acid (UDCA) remains the first-line therapy for primary biliary cholangitis (PBC), the autoimmune nature of PBC underscores the need for treatments targeting immunological pathways that may achieve a cure. E6011, a novel humanized anti-fractalkine monoclonal antibody, has emerged as a potential therapeutic option for PBC. We conducted a randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of E6011 in patients with PBC with an incomplete response to UDCA.</div></div><div><h3>Methods</h3><div>The study was composed of 12-week Double-Blind Phase (placebo, E6011 10 mg/kg/month, 15 mg/kg/month, or 10 mg/kg/every other week [eow]) followed by a 52-week Open-Label Phase. The primary endpoint was the percent change in alkaline phosphatase (ALP) at Week 12.</div></div><div><h3>Results</h3><div>A total of 29 patients were enrolled. Histological evaluation at screening revealed that 83 % of the enrolled patients were classified as Stage 4 according to the Nakanuma Classification. The mean percent changes in ALP at Week 12 were +0.45 % in the placebo, +0.65 % in the 10 mg/kg/month, +1.23 % in the 15 mg/kg/month and +1.19 % in the 10 mg/kg/eow, with no observed trends toward ALP reduction in the E6011 treatment. Based on the interim analysis, the study was discontinued due to a lack of the efficacy. E6011 was generally safe and well tolerated.</div></div><div><h3>Conclusion</h3><div>This study of E6011 failed to meet the primary endpoint in patients with PBC with an incomplete response to UDCA. The advanced histological severity present in more than 80 % of patients at baseline may have contributed to these findings.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100283"},"PeriodicalIF":4.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cross-tissue transcriptome-wide association study reveals novel psoriasis susceptibility genes

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-03-20 DOI: 10.1016/j.jtauto.2025.100286

Fei Yan , Jing Tao , Jie Liu , Yongliang Chen , Zongju Huang

Background

Psoriasis is a chronic, immune-mediated inflammatory skin disorder with a strong genetic component. Although numerous GWAS have identified risk loci, many associated variants lie in non-coding regions, complicating functional interpretation.

Objective

This study aimed to identify novel psoriasis susceptibility genes by integrating large-scale GWAS and eQTL data using a cross-tissue TWAS approach.

Methods

We integrated psoriasis GWAS summary statistics from the FinnGen database with GTEx V8 eQTL data. A cross-tissue TWAS was performed using UTMOST, followed by validation with single-tissue TWAS via FUSION. Conditional and joint analyses were conducted to delineate independent genetic signals, and gene-based analysis was performed using MAGMA. Causal relationships were evaluated using Mendelian randomization (MR) and Bayesian colocalization analyses. Key SNPs were functionally characterized using CADD, GERP++, and RegulomeDB for pathogenicity prediction and regulatory potential assessment. Finally, functional network analysis was conducted using GeneMANIA.

Results

The cross-tissue TWAS identified 259 genes significantly associated with psoriasis (p < 0.05), with 12 remaining significant after FDR correction. Single-tissue TWAS validation revealed 655 significant genes, with an overlap of three protein-coding candidates: POLI, NFKB1, and ZFYVE28. Cross-validation with MAGMA refined the candidate set to NFKB1 and ZFYVE28. MR and colocalization analyses supported a causal relationship for NFKB1 in Skeletal Muscle, Transverse Colon, and Cultured Fibroblasts, and for ZFYVE28 in Subcutaneous Adipose Tissue and Esophageal Mucosa tissues. Functional annotation identified key SNPs including rs4235405, rs3774960, and rs1598856 for NFKB1, and rs1203786 for ZFYVE28, with varying degrees of pathogenicity and regulatory potential. GeneMANIA network analysis further implicated NFKB1 in NF-κB signaling and ZFYVE28 in vesicle-mediated transport.

Conclusion

Our integrative multi-omics approach identifies NFKB1 and ZFYVE28 as novel psoriasis susceptibility genes, providing potential biomarkers and therapeutic targets for this complex disease.

{"title":"Cross-tissue transcriptome-wide association study reveals novel psoriasis susceptibility genes","authors":"Fei Yan , Jing Tao , Jie Liu , Yongliang Chen , Zongju Huang","doi":"10.1016/j.jtauto.2025.100286","DOIUrl":"10.1016/j.jtauto.2025.100286","url":null,"abstract":"<div><h3>Background</h3><div>Psoriasis is a chronic, immune-mediated inflammatory skin disorder with a strong genetic component. Although numerous GWAS have identified risk loci, many associated variants lie in non-coding regions, complicating functional interpretation.</div></div><div><h3>Objective</h3><div>This study aimed to identify novel psoriasis susceptibility genes by integrating large-scale GWAS and eQTL data using a cross-tissue TWAS approach.</div></div><div><h3>Methods</h3><div>We integrated psoriasis GWAS summary statistics from the FinnGen database with GTEx V8 eQTL data. A cross-tissue TWAS was performed using UTMOST, followed by validation with single-tissue TWAS via FUSION. Conditional and joint analyses were conducted to delineate independent genetic signals, and gene-based analysis was performed using MAGMA. Causal relationships were evaluated using Mendelian randomization (MR) and Bayesian colocalization analyses. Key SNPs were functionally characterized using CADD, GERP++, and RegulomeDB for pathogenicity prediction and regulatory potential assessment. Finally, functional network analysis was conducted using GeneMANIA.</div></div><div><h3>Results</h3><div>The cross-tissue TWAS identified 259 genes significantly associated with psoriasis (p < 0.05), with 12 remaining significant after FDR correction. Single-tissue TWAS validation revealed 655 significant genes, with an overlap of three protein-coding candidates: POLI, NFKB1, and ZFYVE28. Cross-validation with MAGMA refined the candidate set to NFKB1 and ZFYVE28. MR and colocalization analyses supported a causal relationship for NFKB1 in Skeletal Muscle, Transverse Colon, and Cultured Fibroblasts, and for ZFYVE28 in Subcutaneous Adipose Tissue and Esophageal Mucosa tissues. Functional annotation identified key SNPs including rs4235405, rs3774960, and rs1598856 for NFKB1, and rs1203786 for ZFYVE28, with varying degrees of pathogenicity and regulatory potential. GeneMANIA network analysis further implicated NFKB1 in NF-κB signaling and ZFYVE28 in vesicle-mediated transport.</div></div><div><h3>Conclusion</h3><div>Our integrative multi-omics approach identifies NFKB1 and ZFYVE28 as novel psoriasis susceptibility genes, providing potential biomarkers and therapeutic targets for this complex disease.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100286"},"PeriodicalIF":4.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the crucial role of CD8+ T cell and endothelial cell interaction in rheumatoid arthritis through the integrated analysis of spatial transcriptomics and bulk/single-cell RNA-seq

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-03-19 DOI: 10.1016/j.jtauto.2025.100285

Yu Lai , Zishao Zhong , Runze Li , Tuliang Liang , Xizi He , Yuan Liu , Hao Yu , Chuanhai Zhang , Yao Xiao , Liang Liu , Hudan Pan

Background

Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease. While the chemokine signaling pathway plays a pivotal role in RA pathogenesis, the specific cellular interactions remain unclear.

Methods

A three-stage analytical framework was implemented. First, to uncover crucial signaling pathways in RA, we conducted an analysis of bulk RNA-seq data (GSE89408) sourced from the Gene Expression Omnibus (GEO) database. Second, utilizing single-cell transcriptome data from GEO (GSE200815 and GSE152805) and EMBL's European Bioinformatics Institute (E-MTAB-8322), we delved into key cell pairs and their ligand-receptor interactions within the chemokine signaling pathway. Third, spatial transcriptome data (SDY2213) from the IMMPORT database were employed to validate the colocalization of these pivotal cell pairs.

Results

Our enrichment analysis of bulk RNA-seq data underscored the chemokine signaling pathway's centrality in RA's pathogenesis. By integrating thirteen single-cell RNA sequencing datasets, we documented a notable elevation in the proportion of most lymphocyte types within RA synovium. The chemokine signaling pathway emerged as one of the primary pathways enriched in genes differentially expressed between RA and osteoarthritis in lymphocytes and CD8⁺ T cells. Cell-cell interaction analysis pinpointed the interaction between CD8⁺ T cells and endothelial cells (ECs) as a distinctive feature of the chemokine signaling pathway. Spatial transcriptome analysis further substantiated the co-localization of CD8⁺ T cells and ECs.

Conclusions

This study highlight CD8⁺ T cell- EC interactions via chemokine signaling as critical drivers of RA progression, potentially promoting leukocyte transendothelial migration and synovial immune infiltration.

{"title":"Unveiling the crucial role of CD8+ T cell and endothelial cell interaction in rheumatoid arthritis through the integrated analysis of spatial transcriptomics and bulk/single-cell RNA-seq","authors":"Yu Lai , Zishao Zhong , Runze Li , Tuliang Liang , Xizi He , Yuan Liu , Hao Yu , Chuanhai Zhang , Yao Xiao , Liang Liu , Hudan Pan","doi":"10.1016/j.jtauto.2025.100285","DOIUrl":"10.1016/j.jtauto.2025.100285","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease. While the chemokine signaling pathway plays a pivotal role in RA pathogenesis, the specific cellular interactions remain unclear.</div></div><div><h3>Methods</h3><div>A three-stage analytical framework was implemented. First, to uncover crucial signaling pathways in RA, we conducted an analysis of bulk RNA-seq data (GSE89408) sourced from the Gene Expression Omnibus (GEO) database. Second, utilizing single-cell transcriptome data from GEO (GSE200815 and GSE152805) and EMBL's European Bioinformatics Institute (E-MTAB-8322), we delved into key cell pairs and their ligand-receptor interactions within the chemokine signaling pathway. Third, spatial transcriptome data (SDY2213) from the IMMPORT database were employed to validate the colocalization of these pivotal cell pairs.</div></div><div><h3>Results</h3><div>Our enrichment analysis of bulk RNA-seq data underscored the chemokine signaling pathway's centrality in RA's pathogenesis. By integrating thirteen single-cell RNA sequencing datasets, we documented a notable elevation in the proportion of most lymphocyte types within RA synovium. The chemokine signaling pathway emerged as one of the primary pathways enriched in genes differentially expressed between RA and osteoarthritis in lymphocytes and CD8<sup>+</sup> T cells. Cell-cell interaction analysis pinpointed the interaction between CD8<sup>+</sup> T cells and endothelial cells (ECs) as a distinctive feature of the chemokine signaling pathway. Spatial transcriptome analysis further substantiated the co-localization of CD8<sup>+</sup> T cells and ECs.</div></div><div><h3>Conclusions</h3><div>This study highlight CD8<sup>+</sup> T cell- EC interactions via chemokine signaling as critical drivers of RA progression, potentially promoting leukocyte transendothelial migration and synovial immune infiltration.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100285"},"PeriodicalIF":4.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The AhR pathway is dysregulated in alopecia areata

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-03-07 DOI: 10.1016/j.jtauto.2025.100282

Arno Belpaire , Annelies Demeyer , Elise Van Caelenberg , Nanja van Geel , Reinhart Speeckaert

Despite significant progress in the treatment of alopecia areata (AA), many aspects of its immune-based pathogenesis remain unexplored. IFN-γ, primarily produced by CD8⁺ T cells and NK cells, is considered central to AA pathogenesis. However, the complex immune signaling network contributes to therapeutic resistance and frequent disease flares after treatment discontinuation. The aryl hydrocarbon receptor (AhR) pathway, upregulated by IFN-γ, modulates Th17 responses, but its inhibitory effects on IFN-γ remain unclear. Although IL-17 levels are elevated in AA, clinical trials indicate that IL-17A inhibitors are ineffective. AhR expression is known to induce immune checkpoints (ICPs) such as PD-1, suggesting a potential role as a negative feedback mechanism. This study investigated AhR expression in lymphocytes from AA patients and its association with clinical and laboratory markers of disease activity. AhR expression was significantly reduced in CD4, CD8, Th1, and Th17 lymphocytes in AA patients compared to healthy controls (p < 0.005), and it correlated inversely with SALTII scores (p < 0.05). ROC analysis showed that AhR levels in CD8 cells could differentiate mild AA from healthy controls with a sensitivity of 82.35 % and specificity of 86.84 %, suggesting potential diagnostic utility. Lower AhR levels were associated with increased IFN-γ+ lymphocytes and decreased IL-17+ immune cells. Interestingly, immune profiles differed between atopic and non-atopic patients: in severe AA, higher AhR expression was linked to increased sPD-1 concentrations, whereas in limited AA, AhR failed to upregulate any investigated ICP. These findings highlight the significant downregulation of the AhR pathway in AA and suggest its potential as a therapeutic target. Future research should explore the development of AhR agonists or antagonists to modulate immune responses in AA.

{"title":"The AhR pathway is dysregulated in alopecia areata","authors":"Arno Belpaire , Annelies Demeyer , Elise Van Caelenberg , Nanja van Geel , Reinhart Speeckaert","doi":"10.1016/j.jtauto.2025.100282","DOIUrl":"10.1016/j.jtauto.2025.100282","url":null,"abstract":"<div><div>Despite significant progress in the treatment of alopecia areata (AA), many aspects of its immune-based pathogenesis remain unexplored. IFN-γ, primarily produced by CD8<sup>+</sup> T cells and NK cells, is considered central to AA pathogenesis. However, the complex immune signaling network contributes to therapeutic resistance and frequent disease flares after treatment discontinuation. The aryl hydrocarbon receptor (AhR) pathway, upregulated by IFN-γ, modulates Th17 responses, but its inhibitory effects on IFN-γ remain unclear. Although IL-17 levels are elevated in AA, clinical trials indicate that IL-17A inhibitors are ineffective. AhR expression is known to induce immune checkpoints (ICPs) such as PD-1, suggesting a potential role as a negative feedback mechanism. This study investigated AhR expression in lymphocytes from AA patients and its association with clinical and laboratory markers of disease activity. AhR expression was significantly reduced in CD4, CD8, Th1, and Th17 lymphocytes in AA patients compared to healthy controls (<em>p</em> < 0.005), and it correlated inversely with SALTII scores (<em>p</em> < 0.05). ROC analysis showed that AhR levels in CD8 cells could differentiate mild AA from healthy controls with a sensitivity of 82.35 % and specificity of 86.84 %, suggesting potential diagnostic utility. Lower AhR levels were associated with increased IFN-γ+ lymphocytes and decreased IL-17+ immune cells. Interestingly, immune profiles differed between atopic and non-atopic patients: in severe AA, higher AhR expression was linked to increased sPD-1 concentrations, whereas in limited AA, AhR failed to upregulate any investigated ICP. These findings highlight the significant downregulation of the AhR pathway in AA and suggest its potential as a therapeutic target. Future research should explore the development of AhR agonists or antagonists to modulate immune responses in AA.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100282"},"PeriodicalIF":4.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pediatric autoimmune diseases in the light of COVID-19 pandemic, A retrospective observational big data study

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-03-06 DOI: 10.1016/j.jtauto.2025.100281

Rim Kasem Ali Sliman , Hilla Cohen , Shereen Shehadeh , Reut Batcir , Yigal Elenberg Alter , Keren Cohen , Ilana Koren , Inbal Halabi , Hussein Sliman , Mohamad Hamad Saied

Background

The COVID-19 pandemic has raised concerns about potential links between SARS-CoV-2 infection and autoimmune diseases. This study investigated changes in the incidence rate (IR) of autoimmune diseases among children following the pandemic's onset.

Methods

A retrospective cross-sectional study analyzed data from Clalit Health Services, Israel's largest healthcare provider, examining the IR of different autoimmune diseases in children aged 0–18. The study compared pre-pandemic (2019) with pandemic/post-pandemic periods (2020–2023), encompassing a cohort of over 1.5 million children.

Results

Significant IR increases were observed across multiple autoimmune diseases. Rheumatic diseases (Juvenile Idiopathic Arthritis, Systemic Lupus Erythematosus, Henoch Schoenlein Purpura (HSP)) showed consistent increases, with HSP demonstrating the most pronounced trend. Endocrine disorders exhibited diverse patterns, with autoimmune thyroid diseases and Type 1 diabetes showing overall increases, while diabetic ketoacidosis exhibited an initial spike followed by a decline. Gastrointestinal diseases displayed heterogeneous patterns; Celiac disease and Ulcerative colitis showed general increases, Crohn's disease showed a downward trend, and autoimmune hepatitis exhibited an initial significant decrease followed by a significant increase. Dermatological conditions, including Psoriasis and Vitiligo, demonstrated consistent elevations throughout 2020–2023. Immune Thrombocytopenia Purpura showed initial decreases followed by significant increases in 2022–2023.

Conclusions

This comprehensive analysis reveals significant changes in pediatric autoimmune disease incidence following the COVID-19 pandemic, suggesting potential associations between SARS-CoV-2 infection and autoimmune dysregulation. The diverse patterns observed across different conditions highlight the complex interplay between viral infection and autoimmunity, emphasizing the need for continued surveillance and investigation of long-term immunological consequences of COVID-19 in pediatric populations.

{"title":"Pediatric autoimmune diseases in the light of COVID-19 pandemic, A retrospective observational big data study","authors":"Rim Kasem Ali Sliman , Hilla Cohen , Shereen Shehadeh , Reut Batcir , Yigal Elenberg Alter , Keren Cohen , Ilana Koren , Inbal Halabi , Hussein Sliman , Mohamad Hamad Saied","doi":"10.1016/j.jtauto.2025.100281","DOIUrl":"10.1016/j.jtauto.2025.100281","url":null,"abstract":"<div><h3>Background</h3><div>The COVID-19 pandemic has raised concerns about potential links between SARS-CoV-2 infection and autoimmune diseases. This study investigated changes in the incidence rate (IR) of autoimmune diseases among children following the pandemic's onset.</div></div><div><h3>Methods</h3><div>A retrospective cross-sectional study analyzed data from Clalit Health Services, Israel's largest healthcare provider, examining the IR of different autoimmune diseases in children aged 0–18. The study compared pre-pandemic (2019) with pandemic/post-pandemic periods (2020–2023), encompassing a cohort of over 1.5 million children.</div></div><div><h3>Results</h3><div>Significant IR increases were observed across multiple autoimmune diseases. Rheumatic diseases (Juvenile Idiopathic Arthritis, Systemic Lupus Erythematosus, Henoch Schoenlein Purpura (HSP)) showed consistent increases, with HSP demonstrating the most pronounced trend. Endocrine disorders exhibited diverse patterns, with autoimmune thyroid diseases and Type 1 diabetes showing overall increases, while diabetic ketoacidosis exhibited an initial spike followed by a decline. Gastrointestinal diseases displayed heterogeneous patterns; Celiac disease and Ulcerative colitis showed general increases, Crohn's disease showed a downward trend, and autoimmune hepatitis exhibited an initial significant decrease followed by a significant increase. Dermatological conditions, including Psoriasis and Vitiligo, demonstrated consistent elevations throughout 2020–2023. Immune Thrombocytopenia Purpura showed initial decreases followed by significant increases in 2022–2023.</div></div><div><h3>Conclusions</h3><div>This comprehensive analysis reveals significant changes in pediatric autoimmune disease incidence following the COVID-19 pandemic, suggesting potential associations between SARS-CoV-2 infection and autoimmune dysregulation. The diverse patterns observed across different conditions highlight the complex interplay between viral infection and autoimmunity, emphasizing the need for continued surveillance and investigation of long-term immunological consequences of COVID-19 in pediatric populations.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100281"},"PeriodicalIF":4.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NETosis: A key player in autoimmunity, COVID-19, and long COVID

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-02-21 DOI: 10.1016/j.jtauto.2025.100280

Diana M. Monsalve , Yeny Acosta-Ampudia , Nicolás Guerrero Acosta , Mariana Celis-Andrade , Ali Şahin , Ahsen Morva Yilmaz , Yehuda Shoenfeld , Carolina Ramírez-Santana

NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.

{"title":"NETosis: A key player in autoimmunity, COVID-19, and long COVID","authors":"Diana M. Monsalve , Yeny Acosta-Ampudia , Nicolás Guerrero Acosta , Mariana Celis-Andrade , Ali Şahin , Ahsen Morva Yilmaz , Yehuda Shoenfeld , Carolina Ramírez-Santana","doi":"10.1016/j.jtauto.2025.100280","DOIUrl":"10.1016/j.jtauto.2025.100280","url":null,"abstract":"<div><div>NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100280"},"PeriodicalIF":4.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding the role of immune-mediated inflammatory disease related cytokines interleukin 17 and 23 in pregnancy: A systematic review

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-02-07 DOI: 10.1016/j.jtauto.2025.100279

Aniek Plug , Liana Barenbrug , Bart G.J. Moerings , Elke M.G. de Jong , Renate G. van der Molen

Background

Pregnancy requires a careful immune balance between tolerance for the semi-allogenic fetus and protection against pathogens. Women with immune-mediated inflammatory diseases (IMIDs), where the interleukin (IL)-23/IL-17 axis plays an important role, often experience changes in disease severity during pregnancy. These changes and the association between disease flares and pregnancy complications, suggests a role for IL-17 and IL-23 in pregnancy.

Methods

We systemically searched PubMed, EMBASE, and Web of Science (March 2024), to assess the role of IL-17 and IL-23 in pregnancy-related in vitro assays, animal or human studies.

Results

Eighty articles (8 in vitro, 11 animal and 61 human studies) were included. Seventy-one studies reported on IL-17 and 16 studies on IL-23. In vitro trophoblast proliferation, migration and invasion was increased in the presence of IL-17, but impaired with IL-23. IL-17 levels were increased in animal models for pregnancy complications. In humans, IL-17 levels seemed to be increased in pregnant women versus non-pregnant women. Additionally, elevated IL-17 levels were associated with pregnancy complications. Although similar trends were found for IL-23, data were limited.

Conclusions

We identified a large, but heterogenic, body of evidence for a significant role of IL-17 in all stages of pregnancy: while an excessive increase seemed to be associated with complications. The limited number of studies prevents firm conclusions on the role of IL-23. Future research is needed to find biomarkers for patients with IMIDs to predict the effect of possible disease flares on pregnancy, and the effect of therapeutic inhibition of IL-17 or IL-23.

{"title":"Understanding the role of immune-mediated inflammatory disease related cytokines interleukin 17 and 23 in pregnancy: A systematic review","authors":"Aniek Plug , Liana Barenbrug , Bart G.J. Moerings , Elke M.G. de Jong , Renate G. van der Molen","doi":"10.1016/j.jtauto.2025.100279","DOIUrl":"10.1016/j.jtauto.2025.100279","url":null,"abstract":"<div><h3>Background</h3><div>Pregnancy requires a careful immune balance between tolerance for the semi-allogenic fetus and protection against pathogens. Women with immune-mediated inflammatory diseases (IMIDs), where the interleukin (IL)-23/IL-17 axis plays an important role, often experience changes in disease severity during pregnancy. These changes and the association between disease flares and pregnancy complications, suggests a role for IL-17 and IL-23 in pregnancy.</div></div><div><h3>Methods</h3><div>We systemically searched PubMed, EMBASE, and Web of Science (March 2024), to assess the role of IL-17 and IL-23 in pregnancy-related <em>in vitro</em> assays, animal or human studies.</div></div><div><h3>Results</h3><div>Eighty articles (8 <em>in vitro</em>, 11 animal and 61 human studies) were included. Seventy-one studies reported on IL-17 and 16 studies on IL-23. <em>In vitro</em> trophoblast proliferation, migration and invasion was increased in the presence of IL-17, but impaired with IL-23. IL-17 levels were increased in animal models for pregnancy complications. In humans, IL-17 levels seemed to be increased in pregnant women versus non-pregnant women. Additionally, elevated IL-17 levels were associated with pregnancy complications. Although similar trends were found for IL-23, data were limited.</div></div><div><h3>Conclusions</h3><div>We identified a large, but heterogenic, body of evidence for a significant role of IL-17 in all stages of pregnancy: while an excessive increase seemed to be associated with complications. The limited number of studies prevents firm conclusions on the role of IL-23. Future research is needed to find biomarkers for patients with IMIDs to predict the effect of possible disease flares on pregnancy, and the effect of therapeutic inhibition of IL-17 or IL-23.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100279"},"PeriodicalIF":4.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-02-04 DOI: 10.1016/j.jtauto.2025.100276

Chen-xing Zhang , You-ying Mao , Yu-pin Tan , Mei-yu Zhang , Kang Shao , Shu-jun Wang , Ping Ji , Jia-yuan Wang , Lei Yin , Ying Wang

Objective

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which is affected by the environmental, genetic factors as well as the immune system. Previous reports have implicated IFN-α in the pathogenesis of SLE. Up to date, however, no research has ever investigated the effect of IFN-α on CD8⁺T cells, which might be implicated in the pathogenesis of SLE. In the present study, we aimed to explore the pathologic role of IFN-α in regard to dysfunction of CD8⁺T cells in SLE.

Methods

Serum level of IFN-α was detected in SLE and healthy controls (HC). Surface expression of lysosome-associated membrane protein 1 (LAMP-1; CD107a) and secretion of granzyme B of CD8⁺T cells was measured in SLE and HC with or without IFN-α co-stimulation/PI3K inhibitor.

Results

Our results demonstrated that there was increased surface expression of CD107a of CD8⁺T cells in SLE patients compared with healthy controls (HC), indicating enhanced cytotoxicity of CD8⁺T cells in SLE patients. Meanwhile, increased secretion of granzyme B was also detected in CD8⁺T cells of SLE compared with HC, which correlated with the disease activity (SLEDAI). Furthermore, elevated serum level of IFN-α in SLE was confirmed in our study. In vitro study, granzyme B secretion by CD8⁺T cells was upregulated upon IFN-α costimulation, which was consistent with enhanced cytotoxicity of CD8⁺T cells upon IFN-α costimulation, as reflected by elevated surface expression of CD107a. PI3K inhibitor reversed increased granzyme B synthesis upon IFN-α costimulation in a dose-dependent manner.

Conclusion

In summary, elevated serum level of IFN-α was responsible for increased secretion of granzyme B and enhanced cytotoxicity of CD8⁺T cells in SLE and this process may be related to PI3K pathway. Relevant molecules and mechanism remains to be explored in the future.

{"title":"Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus","authors":"Chen-xing Zhang , You-ying Mao , Yu-pin Tan , Mei-yu Zhang , Kang Shao , Shu-jun Wang , Ping Ji , Jia-yuan Wang , Lei Yin , Ying Wang","doi":"10.1016/j.jtauto.2025.100276","DOIUrl":"10.1016/j.jtauto.2025.100276","url":null,"abstract":"<div><h3>Objective</h3><div>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which is affected by the environmental, genetic factors as well as the immune system. Previous reports have implicated IFN-α in the pathogenesis of SLE. Up to date, however, no research has ever investigated the effect of IFN-α on CD8<sup>+</sup>T cells, which might be implicated in the pathogenesis of SLE. In the present study, we aimed to explore the pathologic role of IFN-α in regard to dysfunction of CD8<sup>+</sup>T cells in SLE.</div></div><div><h3>Methods</h3><div>Serum level of IFN-α was detected in SLE and healthy controls (HC). Surface expression of lysosome-associated membrane protein 1 (LAMP-1; CD107a) and secretion of granzyme B of CD8<sup>+</sup>T cells was measured in SLE and HC with or without IFN-α co-stimulation/PI3K inhibitor.</div></div><div><h3>Results</h3><div>Our results demonstrated that there was increased surface expression of CD107a of CD8<sup>+</sup>T cells in SLE patients compared with healthy controls (HC), indicating enhanced cytotoxicity of CD8<sup>+</sup>T cells in SLE patients. Meanwhile, increased secretion of granzyme B was also detected in CD8<sup>+</sup>T cells of SLE compared with HC, which correlated with the disease activity (SLEDAI). Furthermore, elevated serum level of IFN-α in SLE was confirmed in our study. In vitro study, granzyme B secretion by CD8<sup>+</sup>T cells was upregulated upon IFN-α costimulation, which was consistent with enhanced cytotoxicity of CD8<sup>+</sup>T cells upon IFN-α costimulation, as reflected by elevated surface expression of CD107a. PI3K inhibitor reversed increased granzyme B synthesis upon IFN-α costimulation in a dose-dependent manner.</div></div><div><h3>Conclusion</h3><div>In summary, elevated serum level of IFN-α was responsible for increased secretion of granzyme B and enhanced cytotoxicity of CD8<sup>+</sup>T cells in SLE and this process may be related to PI3K pathway. Relevant molecules and mechanism remains to be explored in the future.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100276"},"PeriodicalIF":4.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The follow-up of patients with celiac disease

IF 4.7 Q2 IMMUNOLOGY

Journal of Translational Autoimmunity

Pub Date : 2025-01-30 DOI: 10.1016/j.jtauto.2025.100278

Marco Di Tola , Hetty J. Bontkes , Juan Irure-Ventura , Marcos López-Hoyos , Nicola Bizzaro

Celiac disease (CD) is a very common immune-mediated enteropathy resulting from the interaction between dietary gluten and the immune system in genetically predisposed individuals. The immune response leads to intestinal damage, malabsorption and, ultimately, to a broad spectrum of both intestinal and extra-intestinal symptoms. According to current criteria, a proper diagnosis of CD requires an initial phase consisting of clinical case identification and serological screening that, over time, has increased in importance. In most adults and in selected children, the diagnosis is subsequently defined by histological evidence of intestinal damage as a confirmatory test, which usually returns to normal after a suitable period of a gluten-free diet (GFD). The clinical remission and disappearance of circulating antibodies after a GFD further confirm the diagnosis and represent a goal to be achieved to improve the quality of life and reduce the risk of long-term complications. However, although the diagnostic criteria for CD are well defined and described in specific guidelines, the monitoring of CD patients undergoing GFD has been less studied and, consequently, specific guidelines for this phase are still lacking. The aim of this report was to evaluate the classical tools used to monitor the adherence and response to GFD, other non-invasive biomarkers that have been proposed for CD monitoring, and the histological follow-up of CD patients in order to provide a starting point for future discussions on this specific topic.

{"title":"The follow-up of patients with celiac disease","authors":"Marco Di Tola , Hetty J. Bontkes , Juan Irure-Ventura , Marcos López-Hoyos , Nicola Bizzaro","doi":"10.1016/j.jtauto.2025.100278","DOIUrl":"10.1016/j.jtauto.2025.100278","url":null,"abstract":"<div><div>Celiac disease (CD) is a very common immune-mediated enteropathy resulting from the interaction between dietary gluten and the immune system in genetically predisposed individuals. The immune response leads to intestinal damage, malabsorption and, ultimately, to a broad spectrum of both intestinal and extra-intestinal symptoms. According to current criteria, a proper diagnosis of CD requires an initial phase consisting of clinical case identification and serological screening that, over time, has increased in importance. In most adults and in selected children, the diagnosis is subsequently defined by histological evidence of intestinal damage as a confirmatory test, which usually returns to normal after a suitable period of a gluten-free diet (GFD). The clinical remission and disappearance of circulating antibodies after a GFD further confirm the diagnosis and represent a goal to be achieved to improve the quality of life and reduce the risk of long-term complications. However, although the diagnostic criteria for CD are well defined and described in specific guidelines, the monitoring of CD patients undergoing GFD has been less studied and, consequently, specific guidelines for this phase are still lacking. The aim of this report was to evaluate the classical tools used to monitor the adherence and response to GFD, other non-invasive biomarkers that have been proposed for CD monitoring, and the histological follow-up of CD patients in order to provide a starting point for future discussions on this specific topic.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100278"},"PeriodicalIF":4.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0