Pub Date : 2025-01-01Epub Date: 2024-11-25DOI: 10.1111/sji.13426
Çağrı Şakalar, Büşra Kurt, Sedat Sezen, Savaş Kaya
Ovarian cancer is generally diagnosed at late stages. Monoclonal antibodies (MAbs) targeting antigens in ovarian cancer are used in the clinic. Anti-Müllerian hormone receptor type 2 (AMHR2) is a receptor highly expressed in ovarian cancer and it is a potential target antigen for immunotherapy. Extracellular domain of AMHR2 was analysed in terms of 3D structure and physicochemical properties, and 3 peptide sequences (Peptides 1, 7 and 11) were determined as targets. MAb production protocol was performed, and 6 MAb clones showing high affinity for peptides were obtained. P3B1, P10A10, P10B6 and P2A6 clones were for peptide 11 (P11), P2C9 was for P7, and P6C5 was for P1. Antibody isotype of P2A6 was IgG2a and the others were of IgG1 isotype. MAb binding to the native recombinant protein (AMHR2-Fc) was analysed by enzyme-linked immunosorbent assay (ELISA) and MAb binding to AMHR2 expressed by SKOV-3 ovarian cancer cells was analysed by western blot and immunofluorescent staining. P3B1 showed strong, P10A10, P10B6 and P2C9 showed medium affinity for the native protein (AMHR2-Fc). P3B1 and P2C9 showed strong binding in western blot analysis. Clones showed moderate binding in immunoflorescent staining. A complement dependent cytotoxicity (CDC) experiment was conducted using MAbs and transfected SKOV-3 cells. P3B1 induced a significant CDC. Variable regions of P3B1 MAb were sequenced. In conclusion, MAbs for three different regions of AMHR2 were produced. One clone was shown to induce cytotoxicity in ovarian cancer cells and its sequence was determined for future use as a humanised therapeutic MAb.
卵巢癌通常在晚期才被诊断出来。针对卵巢癌抗原的单克隆抗体(MAbs)已用于临床。抗缪勒氏管激素受体2型(AMHR2)是一种在卵巢癌中高度表达的受体,也是一种潜在的免疫疗法靶抗原。研究人员对 AMHR2 的胞外结构域进行了三维结构和理化性质分析,并确定了 3 个肽序列(肽 1、肽 7 和肽 11)作为靶标。进行了 MAb 生产规程,获得了 6 个对肽具有高亲和力的 MAb 克隆。P3B1、P10A10、P10B6 和 P2A6 克隆针对肽 11(P11),P2C9 针对 P7,P6C5 针对 P1。P2A6 的抗体同种型为 IgG2a,其他抗体同种型为 IgG1。酶联免疫吸附试验(ELISA)分析了 MAb 与原生重组蛋白(AMHR2-Fc)的结合情况,Western 印迹和免疫荧光染色分析了 MAb 与 SKOV-3 卵巢癌细胞表达的 AMHR2 的结合情况。P3B1 与原生蛋白(AMHR2-Fc)的亲和力较强,P10A10、P10B6 和 P2C9 与原生蛋白(AMHR2-Fc)的亲和力中等。P3B1 和 P2C9 在 Western 印迹分析中显示出很强的结合力。克隆在免疫荧光染色中显示出中等程度的结合力。使用 MAbs 和转染的 SKOV-3 细胞进行了补体依赖性细胞毒性(CDC)实验。P3B1 诱导了明显的 CDC。对 P3B1 MAb 的可变区进行了测序。总之,针对 AMHR2 的三个不同区域制备了 MAb。其中一个克隆可诱导卵巢癌细胞产生细胞毒性,其序列已被确定,将来可用作人源化治疗 MAb。
{"title":"Production of novel peptide-targeting antibodies for anti-Müllerian hormone receptor 2 and induction of cytotoxicity in ovarian cancer cells.","authors":"Çağrı Şakalar, Büşra Kurt, Sedat Sezen, Savaş Kaya","doi":"10.1111/sji.13426","DOIUrl":"10.1111/sji.13426","url":null,"abstract":"<p><p>Ovarian cancer is generally diagnosed at late stages. Monoclonal antibodies (MAbs) targeting antigens in ovarian cancer are used in the clinic. Anti-Müllerian hormone receptor type 2 (AMHR2) is a receptor highly expressed in ovarian cancer and it is a potential target antigen for immunotherapy. Extracellular domain of AMHR2 was analysed in terms of 3D structure and physicochemical properties, and 3 peptide sequences (Peptides 1, 7 and 11) were determined as targets. MAb production protocol was performed, and 6 MAb clones showing high affinity for peptides were obtained. P3B1, P10A10, P10B6 and P2A6 clones were for peptide 11 (P11), P2C9 was for P7, and P6C5 was for P1. Antibody isotype of P2A6 was IgG2a and the others were of IgG1 isotype. MAb binding to the native recombinant protein (AMHR2-Fc) was analysed by enzyme-linked immunosorbent assay (ELISA) and MAb binding to AMHR2 expressed by SKOV-3 ovarian cancer cells was analysed by western blot and immunofluorescent staining. P3B1 showed strong, P10A10, P10B6 and P2C9 showed medium affinity for the native protein (AMHR2-Fc). P3B1 and P2C9 showed strong binding in western blot analysis. Clones showed moderate binding in immunoflorescent staining. A complement dependent cytotoxicity (CDC) experiment was conducted using MAbs and transfected SKOV-3 cells. P3B1 induced a significant CDC. Variable regions of P3B1 MAb were sequenced. In conclusion, MAbs for three different regions of AMHR2 were produced. One clone was shown to induce cytotoxicity in ovarian cancer cells and its sequence was determined for future use as a humanised therapeutic MAb.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13426"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-11-26DOI: 10.1111/sji.13427
Kittikorn Wangriatisak, Charlotte de Vries, Ravi Kumar Sharma, Wenqi Huang, Caroline Grönwall, Prapaporn Pisitkun, Iva Gunnarsson, Vivianne Malmström, Patchanee Chootong, Francesca Faustini
Altered composition of B-cell compartments is a known feature in patients with systemic lupus erythematosus (SLE). However, deep characterisation of B-cell subsets and their relation to clinical manifestations and disease activity in patients is limited. In this study, we analysed peripheral B-cell subsets phenotype in SLE (n = 35) and healthy controls (HCs, n = 15) by spectral flow cytometry. Disease activity was stratified as inactive (SLEDAI-2 K score 0, n = 2), mild (SLEDAI-2 K score 1-5, n = 12), moderate (SLEDAI-2 K score 6-10, n = 6) or high (SLEDAI-2 K > 10, n = 15). An elevated proportion of activated naive (aNAV), double negative 2 (DN2) and plasmablasts (PB) was observed in patients with high disease activity, compared to other groups of patients and HCs. An upregulation of BTLA was found on both aNAV and DN2 and shifted to lower levels with increasing disease activity. In lupus nephritis (LN) patients (n = 21), aNAV B-cells were especially expanded and positively correlated with DN2 (r = 0.5, p = 0.019) and PB (r = 0.43, p = 0.048). Also, correlation was observed between DN2 and PB (r = 0.6, p = 0.003). Moreover, aNAV frequencies positively correlated with SLEDAI-2 K score, and negatively with the complement fractions C3 and C4. Further, aNAV, DN2 and PB were more expanded in association with positive anti-dsDNA antibodies, rather than other antibody specificities (anti-Sm). These data suggest roles of extrafollicular B cells as key players in disease development of LN. Their association with presence of anti-dsDNA antibodies may indicate their value as candidate biomarkers of kidney involvement in SLE.
B细胞组成的改变是系统性红斑狼疮(SLE)患者的一个已知特征。然而,对B细胞亚群及其与患者临床表现和疾病活动的关系的深入研究还很有限。在这项研究中,我们通过光谱流式细胞术分析了系统性红斑狼疮患者(35 人)和健康对照组(15 人)的外周 B 细胞亚群表型。疾病活动度分为非活动(SLEDAI-2 K 评分 0,n = 2)、轻度(SLEDAI-2 K 评分 1-5,n = 12)、中度(SLEDAI-2 K 评分 6-10,n = 6)或高度(SLEDAI-2 K > 10,n = 15)。与其他组患者和 HCs 相比,在疾病活动度高的患者中观察到活化的幼稚细胞(aNAV)、双阴性 2 型细胞(DN2)和浆细胞(PB)比例升高。在 aNAV 和 DN2 上都发现了 BTLA 的上调,并随着疾病活动性的增加而转为较低水平。在狼疮性肾炎(LN)患者(n = 21)中,aNAV B 细胞尤其增大,并与 DN2(r = 0.5,p = 0.019)和 PB(r = 0.43,p = 0.048)呈正相关。DN2 和 PB 之间也存在相关性(r = 0.6,p = 0.003)。此外,aNAV 频率与 SLEDAI-2 K 评分呈正相关,与补体分数 C3 和 C4 呈负相关。此外,aNAV、DN2 和 PB 与抗dsDNA 抗体阳性相关,而不是与其他抗体特异性(抗-Sm)相关。这些数据表明,滤泡外 B 细胞是 LN 疾病发展的关键因素。它们与抗dsDNA抗体的存在有关,这可能表明它们是系统性红斑狼疮肾脏受累的候选生物标志物。
{"title":"Association between peripheral activated naive and double negative 2 B-cell subsets and clinical parameters in lupus nephritis patients.","authors":"Kittikorn Wangriatisak, Charlotte de Vries, Ravi Kumar Sharma, Wenqi Huang, Caroline Grönwall, Prapaporn Pisitkun, Iva Gunnarsson, Vivianne Malmström, Patchanee Chootong, Francesca Faustini","doi":"10.1111/sji.13427","DOIUrl":"10.1111/sji.13427","url":null,"abstract":"<p><p>Altered composition of B-cell compartments is a known feature in patients with systemic lupus erythematosus (SLE). However, deep characterisation of B-cell subsets and their relation to clinical manifestations and disease activity in patients is limited. In this study, we analysed peripheral B-cell subsets phenotype in SLE (n = 35) and healthy controls (HCs, n = 15) by spectral flow cytometry. Disease activity was stratified as inactive (SLEDAI-2 K score 0, n = 2), mild (SLEDAI-2 K score 1-5, n = 12), moderate (SLEDAI-2 K score 6-10, n = 6) or high (SLEDAI-2 K > 10, n = 15). An elevated proportion of activated naive (aNAV), double negative 2 (DN2) and plasmablasts (PB) was observed in patients with high disease activity, compared to other groups of patients and HCs. An upregulation of BTLA was found on both aNAV and DN2 and shifted to lower levels with increasing disease activity. In lupus nephritis (LN) patients (n = 21), aNAV B-cells were especially expanded and positively correlated with DN2 (r = 0.5, p = 0.019) and PB (r = 0.43, p = 0.048). Also, correlation was observed between DN2 and PB (r = 0.6, p = 0.003). Moreover, aNAV frequencies positively correlated with SLEDAI-2 K score, and negatively with the complement fractions C3 and C4. Further, aNAV, DN2 and PB were more expanded in association with positive anti-dsDNA antibodies, rather than other antibody specificities (anti-Sm). These data suggest roles of extrafollicular B cells as key players in disease development of LN. Their association with presence of anti-dsDNA antibodies may indicate their value as candidate biomarkers of kidney involvement in SLE.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13427"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-27DOI: 10.1111/sji.13410
Katia Mangano, Jose' Francisco Munoz-Valle, Claudia Azucena Palafox-Sánchez, Maria Cristina Petralia, Gian Marco Leone, Paolo Fagone, Ferdinando Nicoletti
This study aimed to investigate the role of TSPAN32, a member of the tetraspanin family, in rheumatoid arthritis (RA). The objective was to assess the expression levels of TSPAN32 in experimental RA models and in RA patient immune cells, exploring its potential as a regulatory factor in RA pathogenesis. The study employed adjuvant-induced arthritis in rats and collagen-induced arthritis (CIA) in mice as experimental models. Ex vivo analyses included evaluating TSPAN32 expression in immune cells at different stages of the disease. In silico data analysis involved examining transcriptomic datasets from drug-naïve and treated RA patients to correlate TSPAN32 expression with clinical parameters. TSPAN32 overexpression experiments in splenocytes from CIA mice aimed to demonstrate its functional impact on antigen-specific immune responses. The animal models revealed a significant downregulation of TSPAN32, particularly in synovial-infiltrating T cells. Also, TSPAN32 overexpression inhibited pro-inflammatory cytokine production in splenocytes. In RA patients, TSPAN32 was consistently downregulated in circulating and synovial-infiltrating T cells, as well as in CD8+ T cells, B cells and NK cells. Drug treatment did not significantly alter TSPAN32 levels. Negative correlations were observed between TSPAN32 expression and inflammatory markers (CRP, ESR) and clinical scores (SDAI) in RA patients. This study suggests that reduced TSPAN32 expression characterizes pathogenic T-cell populations in RA, highlighting its potential as biomarker for inflammation and disease activity. TSPAN32 may play a crucial role in shaping adaptive immune responses in RA, opening avenues for novel therapeutic strategies targeting this tetraspanin family member.
本研究旨在探讨四泛蛋白家族成员 TSPAN32 在类风湿性关节炎(RA)中的作用。目的是评估TSPAN32在实验性RA模型和RA患者免疫细胞中的表达水平,探索其作为RA发病机制调控因子的潜力。研究采用佐剂诱导的大鼠关节炎和胶原诱导的小鼠关节炎(CIA)作为实验模型。体内外分析包括评估疾病不同阶段免疫细胞中 TSPAN32 的表达。硅学数据分析包括检查未接受过药物治疗和接受过药物治疗的 RA 患者的转录组数据集,以将 TSPAN32 的表达与临床参数联系起来。TSPAN32在CIA小鼠脾细胞中的过表达实验旨在证明其对抗原特异性免疫反应的功能影响。动物模型显示 TSPAN32 的表达明显下调,尤其是在滑膜浸润 T 细胞中。此外,TSPAN32 的过表达抑制了脾细胞中促炎细胞因子的产生。在 RA 患者中,TSPAN32 在循环和滑膜浸润 T 细胞以及 CD8+ T 细胞、B 细胞和 NK 细胞中持续下调。药物治疗并未明显改变 TSPAN32 的水平。在 RA 患者中,TSPAN32 的表达与炎症指标(CRP、ESR)和临床评分(SDAI)之间呈负相关。这项研究表明,TSPAN32表达的减少是RA致病性T细胞群的特征,突出了其作为炎症和疾病活动生物标志物的潜力。TSPAN32可能在形成RA的适应性免疫反应中起着至关重要的作用,为针对这种四泛蛋白家族成员的新型治疗策略开辟了道路。
{"title":"Tetraspanin32 (TSPAN32) is downregulated in rheumatoid arthritis: Evidence from animal models and patients.","authors":"Katia Mangano, Jose' Francisco Munoz-Valle, Claudia Azucena Palafox-Sánchez, Maria Cristina Petralia, Gian Marco Leone, Paolo Fagone, Ferdinando Nicoletti","doi":"10.1111/sji.13410","DOIUrl":"10.1111/sji.13410","url":null,"abstract":"<p><p>This study aimed to investigate the role of TSPAN32, a member of the tetraspanin family, in rheumatoid arthritis (RA). The objective was to assess the expression levels of TSPAN32 in experimental RA models and in RA patient immune cells, exploring its potential as a regulatory factor in RA pathogenesis. The study employed adjuvant-induced arthritis in rats and collagen-induced arthritis (CIA) in mice as experimental models. Ex vivo analyses included evaluating TSPAN32 expression in immune cells at different stages of the disease. In silico data analysis involved examining transcriptomic datasets from drug-naïve and treated RA patients to correlate TSPAN32 expression with clinical parameters. TSPAN32 overexpression experiments in splenocytes from CIA mice aimed to demonstrate its functional impact on antigen-specific immune responses. The animal models revealed a significant downregulation of TSPAN32, particularly in synovial-infiltrating T cells. Also, TSPAN32 overexpression inhibited pro-inflammatory cytokine production in splenocytes. In RA patients, TSPAN32 was consistently downregulated in circulating and synovial-infiltrating T cells, as well as in CD8+ T cells, B cells and NK cells. Drug treatment did not significantly alter TSPAN32 levels. Negative correlations were observed between TSPAN32 expression and inflammatory markers (CRP, ESR) and clinical scores (SDAI) in RA patients. This study suggests that reduced TSPAN32 expression characterizes pathogenic T-cell populations in RA, highlighting its potential as biomarker for inflammation and disease activity. TSPAN32 may play a crucial role in shaping adaptive immune responses in RA, opening avenues for novel therapeutic strategies targeting this tetraspanin family member.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13410"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-29DOI: 10.1111/sji.13416
Zhao Wang, Khawar Ali Shahzad, Xuran Li, Boyu Cai, Maoxiang Xu, Jiaojiao Li, Fei Tan
Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown promising immunomodulatory capabilities for a variety of clinical conditions. However, the potential regulatory mechanisms of MSC-EVs in allergic rhinitis (AR) remain unexplored. The present study was designed to investigate the immunomodulatory effect of MSC-EVs in patients with AR. Peripheral blood mononuclear cells (PBMCs) were isolated from AR patients. The number of peripheral CD4+Foxp3+IL-17+, CD4+Foxp3+IL-17- and CD4+Foxp3-IL-17+ T cells in healthy controls and AR patients were evaluated using flow cytometry. Therapeutic effect of MSC-EVs was determined by detecting IFN-γ, IL-4, IL-17 and IL-10 cytokines in supernatant by ELISA and flow cytometry. The mean fluorescence intensity (MFI) was calculated in PBMCs for IL-10, IL-17 and TGF-β on T cells after MSC-EVs treatment. Bioinformatic analysis of microRNA was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. CD4+Foxp3+IL-17+ T cells expression in PBMCs was higher in the AR group and the balance of Treg/Th17 was tilted towards Th17 cells. Supernatant from AR patients revealed that MSC-EVs treatment upregulated IL-10 and IFN-γ, and downregulated IL-4 and IL-17. EVs treatment effectively re-established Th1(CD4+IFN-γ+cells)/Th2(CD4+IL-4+cells) balance, reduced CD4+IL-17+ and increased CD4+IL-10+ and CD4+TGF-β+ cells. The MFI of IL-10 and TGF-β in CD4+CD25+CD127- T cells were higher, whereas lower levels of IL-17 were observed. Bioinformatic analysis revealed that the TGF-β, Wnt signalling pathways and STAT5 transcription factor might mechanistically support the immunomodulatory effect of MSC-EVs. This study presents the immunomodulatory effect of MSC-EVs in PBMCs from AR patients. The results provide a new therapeutic strategy for AR.
间充质干细胞衍生的细胞外囊泡(MSC-EVs)已在多种临床疾病中显示出良好的免疫调节能力。然而,间充质干细胞-细胞外小泡在过敏性鼻炎(AR)中的潜在调节机制仍有待探索。本研究旨在探讨间充质干细胞-EVs对过敏性鼻炎患者的免疫调节作用。研究人员从 AR 患者体内分离出外周血单核细胞(PBMCs)。使用流式细胞术评估了健康对照组和 AR 患者外周 CD4+Foxp3+IL-17+、CD4+Foxp3+IL-17- 和 CD4+Foxp3-IL-17+ T 细胞的数量。通过 ELISA 和流式细胞术检测上清液中的 IFN-γ、IL-4、IL-17 和 IL-10 细胞因子,确定间充质干细胞-EVs 的治疗效果。计算了间充质干细胞-EVs 处理后 T 细胞上 IL-10、IL-17 和 TGF-β 在 PBMCs 中的平均荧光强度(MFI)。通过基因本体(GO)和京都基因组百科全书(KEGG)分析对 microRNA 进行生物信息学分析。AR 组 PBMCs 中 CD4+Foxp3+IL-17+ T 细胞的表达量更高,Treg/Th17 的平衡向 Th17 细胞倾斜。AR患者的上清液显示,间充质干细胞-EVs治疗可上调IL-10和IFN-γ,下调IL-4和IL-17。EVs处理能有效重建Th1(CD4+IFN-γ+细胞)/Th2(CD4+IL-4+细胞)平衡,减少CD4+IL-17+,增加CD4+IL-10+和CD4+TGF-β+细胞。CD4+CD25+CD127- T细胞中IL-10和TGF-β的MFI较高,而IL-17的水平较低。生物信息学分析表明,TGF-β、Wnt 信号通路和 STAT5 转录因子可能从机理上支持间充质干细胞-EVs 的免疫调节作用。本研究揭示了间充质干细胞-EVs 对 AR 患者 PBMCs 的免疫调节作用。研究结果为AR提供了一种新的治疗策略。
{"title":"Immunomodulatory effect of mesenchymal stem cells-derived extracellular vesicles to modulate the regulatory T cells and Th1/Th2 imbalance in peripheral blood mononuclear cells of patients with allergic rhinitis.","authors":"Zhao Wang, Khawar Ali Shahzad, Xuran Li, Boyu Cai, Maoxiang Xu, Jiaojiao Li, Fei Tan","doi":"10.1111/sji.13416","DOIUrl":"10.1111/sji.13416","url":null,"abstract":"<p><p>Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown promising immunomodulatory capabilities for a variety of clinical conditions. However, the potential regulatory mechanisms of MSC-EVs in allergic rhinitis (AR) remain unexplored. The present study was designed to investigate the immunomodulatory effect of MSC-EVs in patients with AR. Peripheral blood mononuclear cells (PBMCs) were isolated from AR patients. The number of peripheral CD4<sup>+</sup>Foxp3<sup>+</sup>IL-17<sup>+</sup>, CD4<sup>+</sup>Foxp3<sup>+</sup>IL-17<sup>-</sup> and CD4<sup>+</sup>Foxp3<sup>-</sup>IL-17<sup>+</sup> T cells in healthy controls and AR patients were evaluated using flow cytometry. Therapeutic effect of MSC-EVs was determined by detecting IFN-γ, IL-4, IL-17 and IL-10 cytokines in supernatant by ELISA and flow cytometry. The mean fluorescence intensity (MFI) was calculated in PBMCs for IL-10, IL-17 and TGF-β on T cells after MSC-EVs treatment. Bioinformatic analysis of microRNA was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. CD4<sup>+</sup>Foxp3<sup>+</sup>IL-17<sup>+</sup> T cells expression in PBMCs was higher in the AR group and the balance of Treg/Th17 was tilted towards Th17 cells. Supernatant from AR patients revealed that MSC-EVs treatment upregulated IL-10 and IFN-γ, and downregulated IL-4 and IL-17. EVs treatment effectively re-established Th1(CD4<sup>+</sup>IFN-γ<sup>+</sup>cells)/Th2(CD4<sup>+</sup>IL-4<sup>+</sup>cells) balance, reduced CD4<sup>+</sup>IL-17<sup>+</sup> and increased CD4<sup>+</sup>IL-10<sup>+</sup> and CD4<sup>+</sup>TGF-β<sup>+</sup> cells. The MFI of IL-10 and TGF-β in CD4<sup>+</sup>CD25<sup>+</sup>CD127<sup>-</sup> T cells were higher, whereas lower levels of IL-17 were observed. Bioinformatic analysis revealed that the TGF-β, Wnt signalling pathways and STAT5 transcription factor might mechanistically support the immunomodulatory effect of MSC-EVs. This study presents the immunomodulatory effect of MSC-EVs in PBMCs from AR patients. The results provide a new therapeutic strategy for AR.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13416"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-11-06DOI: 10.1111/sji.13421
Julia Maroto-García, Minerva Mañez, Ana Martínez-Escribano, Ahlam Hachmaoui-Ridaoui, Carmen Ortiz, Carmen Ábalos-García, Inmaculada Gónzález, Ángela García de la Torre, Maximiliano Ruiz-Galdón
Multiple sclerosis (MS) diagnosis includes the presence of restricted oligoclonal bands (OCB) in cerebrospinal fluid (CSF), but it has several limitations, as it is an observer-dependent time-consuming technique and offers a dichotomous result. Thus kappa free light chains (KFLC) have emerged as a quantitative alternative. However, the cut-off values for KFLC have not been well established yet and it is not clear if differences between sexes exist. We aim to evaluate these and to compare the diagnostic accuracy of KFLC concentrations and their related indexes versus OCB. For that purpose, paired CSF and serum samples were collected and immediately processed for albumin, total protein, immunoglobulins and OCB, then frozen at -20°C. KFLC was measured in a BN II (Siemens Healthineers, Germany). KFLC-derived indexes were calculated. Diagnostic accuracy was evaluated by the area under the curve (AUC), Youden's index and odds ratio. From the 193 patients included, 56 were classified as MS according to the 2017 McDonald criteria. K-index, Q KFLC and Reiber's diagram showed good accuracy in MS diagnosis when studied distinguishing between sexes, similar to OCB. Cut-offs for K-index and Q KFLC change substantially between sex having the highest AUC similar than OCB. A sex-dependent algorithm combining the use of K-index, Q KFLC and OCB yields the highest diagnostic accuracy. In conclusion, CSF KFLC measurement is a rapid, quantitative and easy-to-standardize tool that used through the proposed sex-dependent algorithm may reduce the number of manual OCB tests performed.
{"title":"A sex-dependent algorithm including kappa free light chain for multiple sclerosis diagnosis.","authors":"Julia Maroto-García, Minerva Mañez, Ana Martínez-Escribano, Ahlam Hachmaoui-Ridaoui, Carmen Ortiz, Carmen Ábalos-García, Inmaculada Gónzález, Ángela García de la Torre, Maximiliano Ruiz-Galdón","doi":"10.1111/sji.13421","DOIUrl":"10.1111/sji.13421","url":null,"abstract":"<p><p>Multiple sclerosis (MS) diagnosis includes the presence of restricted oligoclonal bands (OCB) in cerebrospinal fluid (CSF), but it has several limitations, as it is an observer-dependent time-consuming technique and offers a dichotomous result. Thus kappa free light chains (KFLC) have emerged as a quantitative alternative. However, the cut-off values for KFLC have not been well established yet and it is not clear if differences between sexes exist. We aim to evaluate these and to compare the diagnostic accuracy of KFLC concentrations and their related indexes versus OCB. For that purpose, paired CSF and serum samples were collected and immediately processed for albumin, total protein, immunoglobulins and OCB, then frozen at -20°C. KFLC was measured in a BN II (Siemens Healthineers, Germany). KFLC-derived indexes were calculated. Diagnostic accuracy was evaluated by the area under the curve (AUC), Youden's index and odds ratio. From the 193 patients included, 56 were classified as MS according to the 2017 McDonald criteria. K-index, Q KFLC and Reiber's diagram showed good accuracy in MS diagnosis when studied distinguishing between sexes, similar to OCB. Cut-offs for K-index and Q KFLC change substantially between sex having the highest AUC similar than OCB. A sex-dependent algorithm combining the use of K-index, Q KFLC and OCB yields the highest diagnostic accuracy. In conclusion, CSF KFLC measurement is a rapid, quantitative and easy-to-standardize tool that used through the proposed sex-dependent algorithm may reduce the number of manual OCB tests performed.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13421"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-08DOI: 10.1111/sji.13411
Mario Sestan, Todor Arsov, Nastasia Kifer, Marijan Frkovic, Danica Grguric, Julia Ellyard, Matthew Cook, Carola G Vinuesa, Marija Jelusic
The purpose of this study was to identify new and low-frequency gene variants using whole exome sequencing (WES) in patients with childhood-onset systemic lupus erythematosus (cSLE), that may be involved in the pathogenesis of SLE. We performed WES on selected 17 trios (in some cases including other informative family members) in which the proband presented with severe, atypical clinical features, resistance to conventional therapy, a family pattern of occurrence and/or syndromic characteristics. After performing WES and analysis of gene variants, 17 novel and/or low-frequency variants were identified in 7 patients. One variant was classified as pathogenic (KMT2D, NM_003482.3:c.8626delC, predicted to truncate the protein p.(Gln2876Serfs*34)) and two as likely pathogenic according to the American College of Medical Genetics and Genomics classification guidelines (ADAR, NM_001111.3:c.2815A>G, predicted to encode p.(Ile939Val); BLK, NM_001715.2:c.211G>A, predicted to encode p.(Ala71Thr)). The other variants remain of uncertain significance at this point of time. WES is an important diagnostic and research instrument, producing a growing list of likely genes and gene variants that may be of relevance in the pathogenesis of cSLE and potentially point to novel therapeutic targets.
本研究的目的是利用全外显子组测序(WES)在儿童期发病的系统性红斑狼疮(cSLE)患者中鉴定可能与系统性红斑狼疮发病机制有关的新的低频基因变异。我们对筛选出的 17 个三联体(在某些情况下包括其他有信息的家庭成员)进行了 WES 测序,这些三联体的原型具有严重的非典型临床特征、对常规治疗有抵抗力、家族发病模式和/或综合征特征。经过 WES 和基因变异分析,在 7 名患者中发现了 17 个新型和/或低频变异。根据美国医学遗传学和基因组学学院(American College of Medical Genetics and Genomics)的分类指南,其中一个变异被归类为致病变异(KMT2D,NM_003482.3:c.8626delC,预测为截短蛋白 p.(Gln2876Serfs*34)),两个变异被归类为可能致病变异(ADAR,NM_001111.3:c.2815A>G,预测为编码蛋白 p.(Gln2876Serfs*34))。A>G,预测编码 p.(Ile939Val);BLK,NM_001715.2:c.211G>A,预测编码 p.(Ala71Thr))。其他变异的意义目前仍不确定。WES 是一种重要的诊断和研究工具,它能发现越来越多可能与系统性红斑狼疮发病机制有关的基因和基因变异,并有可能找到新的治疗靶点。
{"title":"Whole exome sequencing in patients with childhood-onset systemic lupus erythematosus: Results from a Croatian national study.","authors":"Mario Sestan, Todor Arsov, Nastasia Kifer, Marijan Frkovic, Danica Grguric, Julia Ellyard, Matthew Cook, Carola G Vinuesa, Marija Jelusic","doi":"10.1111/sji.13411","DOIUrl":"10.1111/sji.13411","url":null,"abstract":"<p><p>The purpose of this study was to identify new and low-frequency gene variants using whole exome sequencing (WES) in patients with childhood-onset systemic lupus erythematosus (cSLE), that may be involved in the pathogenesis of SLE. We performed WES on selected 17 trios (in some cases including other informative family members) in which the proband presented with severe, atypical clinical features, resistance to conventional therapy, a family pattern of occurrence and/or syndromic characteristics. After performing WES and analysis of gene variants, 17 novel and/or low-frequency variants were identified in 7 patients. One variant was classified as pathogenic (KMT2D, NM_003482.3:c.8626delC, predicted to truncate the protein p.(Gln2876Serfs*34)) and two as likely pathogenic according to the American College of Medical Genetics and Genomics classification guidelines (ADAR, NM_001111.3:c.2815A>G, predicted to encode p.(Ile939Val); BLK, NM_001715.2:c.211G>A, predicted to encode p.(Ala71Thr)). The other variants remain of uncertain significance at this point of time. WES is an important diagnostic and research instrument, producing a growing list of likely genes and gene variants that may be of relevance in the pathogenesis of cSLE and potentially point to novel therapeutic targets.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13411"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osteomyelitis is a bone inflammation initiated by invading pathogens. Macrophages and inflammation play essential roles in osteomyelitis. F-Box and WD repeat domain containing 7 (Fbxw7) is a tumour suppressor and E3 ubiquitin ligase. In the present study, the potential roles of Fbxw7 in osteomyelitis were explored. The mRNA level of Fbxw7 was measured in bone marrow cells from patients with osteomyelitis and Staphylococcus aureus (S. aureus)-infected macrophages. The conditional knockout mice with Fbxw7 deficiency in myeloid cells were generated. The expression of interleukin (IL)-6, IL-23a and nitric oxide synthase 2 (Nos2) was measured in S. aureus-infected Fbxw7-deficient bone marrow-derived macrophages (BMDMs). The body weight loss, bacterial burden, bone loss and formation and serum level of IL-6, IL-23 and TNF-α were measured in S. aureus-infected Fbxw7 conditional KO mice. The interacting partners of Fbxw7 were predicted using STRING and the interaction were tested. Elevated expression of Fbxw7 was observed in bone marrow cells from patients with osteomyelitis and in S. aureus-infected macrophages. The expression of IL-6, IL-23a and Nos2 was remarkably suppressed in S. aureus-infected Fbxw7-deficient BMDMs. Fbxw7 conditional knockout mice had less body weight loss, higher bacterial burden, less bone loss and formation and decreased serum level of cytokines. Fbxw7 interacted with MYB. S. aureus-infected Fbxw7-deficient BMDMs had higher level of MYB and less ubiquitination of MYB. Fbxw7 promotes osteomyelitis symptoms by regulating ubiquitination and stability of MYB.
{"title":"F-Box and WD repeat domain containing 7 induces infectious osteomyelitis by regulating MYB stability and ubiquitination.","authors":"Yongbo Wan, Gehan Jiang, Haojie Shan, Yiwei Lin, Wenyang Xia, Fuli Yin, Chaolai Jiang, Zhongmin Shi","doi":"10.1111/sji.13414","DOIUrl":"10.1111/sji.13414","url":null,"abstract":"<p><p>Osteomyelitis is a bone inflammation initiated by invading pathogens. Macrophages and inflammation play essential roles in osteomyelitis. F-Box and WD repeat domain containing 7 (Fbxw7) is a tumour suppressor and E3 ubiquitin ligase. In the present study, the potential roles of Fbxw7 in osteomyelitis were explored. The mRNA level of Fbxw7 was measured in bone marrow cells from patients with osteomyelitis and Staphylococcus aureus (S. aureus)-infected macrophages. The conditional knockout mice with Fbxw7 deficiency in myeloid cells were generated. The expression of interleukin (IL)-6, IL-23a and nitric oxide synthase 2 (Nos2) was measured in S. aureus-infected Fbxw7-deficient bone marrow-derived macrophages (BMDMs). The body weight loss, bacterial burden, bone loss and formation and serum level of IL-6, IL-23 and TNF-α were measured in S. aureus-infected Fbxw7 conditional KO mice. The interacting partners of Fbxw7 were predicted using STRING and the interaction were tested. Elevated expression of Fbxw7 was observed in bone marrow cells from patients with osteomyelitis and in S. aureus-infected macrophages. The expression of IL-6, IL-23a and Nos2 was remarkably suppressed in S. aureus-infected Fbxw7-deficient BMDMs. Fbxw7 conditional knockout mice had less body weight loss, higher bacterial burden, less bone loss and formation and decreased serum level of cytokines. Fbxw7 interacted with MYB. S. aureus-infected Fbxw7-deficient BMDMs had higher level of MYB and less ubiquitination of MYB. Fbxw7 promotes osteomyelitis symptoms by regulating ubiquitination and stability of MYB.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13414"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-30DOI: 10.1111/sji.13418
Sevgi Bilgic-Eltan, Razin Amirov, Royale Babayeva, Melek Yorgun Altunbas, Tuba Karakurt, Salim Can, Ezgi Yalcin Gungoren, Selcen Bozkurt, Necmiye Ozturk, Mehmet Cihangir Catak, Alper Bulutoglu, Gizem Onder, Yuk Yin Ng, Ozden Hatırnaz Ng, Elif Karakoc-Aydiner, Ahmet Oguzhan Ozen, Safa Baris
Infants with congenital heart disease (CHD) often undergo thymectomy during corrective cardiac surgery (CCS). The long-term immunological effects remain controversial, with concerns regarding increased susceptibility to infections, allergies, autoimmunity due to compromised immune tolerance mechanisms. This study aims to elucidate the long-term immunological effects of early thymectomy. We enrolled 22 patients who underwent thymectomy in infancy and were followed up in the Pediatric Allergy and Immunology Clinic at Marmara University. We performed demographic characteristics and detailed immunological evaluation, including immunoglobulins, vaccine responses, lymphocyte subset analyses, upregulation, proliferation of T cells and T-cell receptor excision circles (TRECs). Sixteen patients had a history of infection, including six serious infections, all in the first year. Lymphopenia was observed in 27% of patients, with a significant decrease in naive CD4+ and recent thymic emigrant T cells counts and an increase in the proportion of memory T-cells, indicating premature immune senescence. Low levels of IgG, IgA and IgM were found in 36%, 40% and 22% of patients respectively. Vaccine responses were positive in 90% of patients. TREC levels were low in all 10 patients analysed. Seven of nine patients had normal proliferation. Twenty-two percent of patients had allergic disease, and autoimmunity was not observed. Early thymectomy leads to permanent immunological changes that are indicative of early immunosenescence. It is recommended to preserve thymic tissue during surgery and requires long-term follow-up in terms of findings such as allergy and autoimmunity as well as infections due to impaired immune tolerance mechanisms.
{"title":"Long-term immunological changes after corrective cardiac surgery.","authors":"Sevgi Bilgic-Eltan, Razin Amirov, Royale Babayeva, Melek Yorgun Altunbas, Tuba Karakurt, Salim Can, Ezgi Yalcin Gungoren, Selcen Bozkurt, Necmiye Ozturk, Mehmet Cihangir Catak, Alper Bulutoglu, Gizem Onder, Yuk Yin Ng, Ozden Hatırnaz Ng, Elif Karakoc-Aydiner, Ahmet Oguzhan Ozen, Safa Baris","doi":"10.1111/sji.13418","DOIUrl":"10.1111/sji.13418","url":null,"abstract":"<p><p>Infants with congenital heart disease (CHD) often undergo thymectomy during corrective cardiac surgery (CCS). The long-term immunological effects remain controversial, with concerns regarding increased susceptibility to infections, allergies, autoimmunity due to compromised immune tolerance mechanisms. This study aims to elucidate the long-term immunological effects of early thymectomy. We enrolled 22 patients who underwent thymectomy in infancy and were followed up in the Pediatric Allergy and Immunology Clinic at Marmara University. We performed demographic characteristics and detailed immunological evaluation, including immunoglobulins, vaccine responses, lymphocyte subset analyses, upregulation, proliferation of T cells and T-cell receptor excision circles (TRECs). Sixteen patients had a history of infection, including six serious infections, all in the first year. Lymphopenia was observed in 27% of patients, with a significant decrease in naive CD4<sup>+</sup> and recent thymic emigrant T cells counts and an increase in the proportion of memory T-cells, indicating premature immune senescence. Low levels of IgG, IgA and IgM were found in 36%, 40% and 22% of patients respectively. Vaccine responses were positive in 90% of patients. TREC levels were low in all 10 patients analysed. Seven of nine patients had normal proliferation. Twenty-two percent of patients had allergic disease, and autoimmunity was not observed. Early thymectomy leads to permanent immunological changes that are indicative of early immunosenescence. It is recommended to preserve thymic tissue during surgery and requires long-term follow-up in terms of findings such as allergy and autoimmunity as well as infections due to impaired immune tolerance mechanisms.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13418"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-11-06DOI: 10.1111/sji.13422
Irina Maslovarić, Dejana Kosanović, Dragana Marković, Milan Prodanović, Olivera Savić, Ana Janjušević, Vesna Ilić, Rajna Minić
The progression of monoclonal gammopathies is affected by a range of factors, including the microenvironment surrounding plasma cells. It is recognized that TGF-β1 plays a distinct role in stimulating IgA production. Hence, this study aims to investigate whether individuals with serum IgA monoclonal immunoglobulins (paraproteins) exhibit elevated total TGF-β1 levels compared to those with IgG or IgM paraproteins. To achieve this goal, individuals with a positive laboratory finding of monoclonal gammopathy were segregated according to the paraprotein class as well as according to the type of the light chain. Total TGF-β1 levels were assessed in blood serum samples containing IgG (n = 50), IgA (n = 46), and IgM (n = 31) paraproteins. Elevated level of TGF-β1 was confirmed in sera with IgA paraproteins (median 25.8 ng/mL; interquartile range IQR: 19.0-33.7) compared to those having IgG (median: 18.2 ng/mL; IQR: 14.3-22.1; p < 0.001) or IgM paraproteins (21.5 ng/mL; IQR: 15.0-27.4; p = 0.043). Also, a higher TGF-β1 level was detected in sera with IgMλ than those with IgMκ paraproteins (p = 0.043). This research affirms the role of TGF-β1 in the pathophysiology of IgA monoclonal gammopathies and the potential switch towards the IgA isotype, known for a less favourable prognosis.
单克隆抗体病的发展受到一系列因素的影响,包括浆细胞周围的微环境。人们认识到,TGF-β1 在刺激 IgA 生成方面发挥着独特的作用。因此,本研究旨在探讨与 IgG 或 IgM 副蛋白患者相比,血清中 IgA 单克隆免疫球蛋白(副蛋白)患者是否表现出总 TGF-β1 水平升高。为了实现这一目标,我们根据副蛋白类别和轻链类型对实验室发现单克隆抗体阳性的个体进行了分离。在含有 IgG(50 人)、IgA(46 人)和 IgM(31 人)副蛋白的血清样本中评估 TGF-β1 总含量。与含有 IgG 的血清(中位数:18.2 ng/mL;四分位间距 IQR:19.0-33.7)相比,含有 IgA 副蛋白的血清中 TGF-β1 水平升高(中位数:25.8 ng/mL;四分位间距 IQR:19.0-33.7):18.2纳克/毫升;四分位数间距:14.3-22.1;p
{"title":"IgA monoclonal gammopathies are accompanied by higher total TGF-β1 levels than IgG or IgM monoclonal gammopathies.","authors":"Irina Maslovarić, Dejana Kosanović, Dragana Marković, Milan Prodanović, Olivera Savić, Ana Janjušević, Vesna Ilić, Rajna Minić","doi":"10.1111/sji.13422","DOIUrl":"10.1111/sji.13422","url":null,"abstract":"<p><p>The progression of monoclonal gammopathies is affected by a range of factors, including the microenvironment surrounding plasma cells. It is recognized that TGF-β1 plays a distinct role in stimulating IgA production. Hence, this study aims to investigate whether individuals with serum IgA monoclonal immunoglobulins (paraproteins) exhibit elevated total TGF-β1 levels compared to those with IgG or IgM paraproteins. To achieve this goal, individuals with a positive laboratory finding of monoclonal gammopathy were segregated according to the paraprotein class as well as according to the type of the light chain. Total TGF-β1 levels were assessed in blood serum samples containing IgG (n = 50), IgA (n = 46), and IgM (n = 31) paraproteins. Elevated level of TGF-β1 was confirmed in sera with IgA paraproteins (median 25.8 ng/mL; interquartile range IQR: 19.0-33.7) compared to those having IgG (median: 18.2 ng/mL; IQR: 14.3-22.1; p < 0.001) or IgM paraproteins (21.5 ng/mL; IQR: 15.0-27.4; p = 0.043). Also, a higher TGF-β1 level was detected in sera with IgMλ than those with IgMκ paraproteins (p = 0.043). This research affirms the role of TGF-β1 in the pathophysiology of IgA monoclonal gammopathies and the potential switch towards the IgA isotype, known for a less favourable prognosis.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13422"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-02DOI: 10.1111/sji.13409
Laura Gregersen, Pernille Dyhre Jessen, Helene Wiencke Lund, Silja Hvid Overgaard, Zainab Hikmat, Torkell Ellingsen, Jens Kjeldsen, Andreas Kristian Pedersen, Sofie Ronja Petersen, Mohamad Jawhara, Anders Bathum Nexøe, Anette Bygum, Christian Lodberg Hvas, Jens Frederik Dahlerup, Frederik Olof Bergenheim, Henning Glerup, Rikke Holm Henriksen, Tanja Guldmann, Lone Hvid, Jacob Brodersen, Heidi Lausten Munk, Natalia Pedersen, Sanaz Saboori, Ole Haagen Nielsen, Berit Lillenthal Heitmann, Thorhallur Ingi Haldorsson, Robin Christensen, Vibeke Andersen
Chronic inflammatory diseases (CIDs) pose a growing healthcare challenge, with a substantial proportion of patients showing inadequate response to biological treatment. There is renewed interest in dietary changes to optimize treatment regimens, with a growing body of evidence suggesting beneficial effects with adherence to a gluten-free diet. This study compared the likelihood of achieving clinical response to biological treatment after 14-16 weeks in patients with CID with high versus low-to-medium gluten intake. Secondary outcomes of interest included changes in disease activity, health-related quality of life and C-reactive protein. The study was a multicentre prospective cohort of 193 participants with a CID diagnosis (i.e. Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis or Psoriasis) who initiated biological treatment between 2017 and 2020. Participants were stratified based on their habitual gluten intake: the upper 33.3% (high gluten intake) and the remaining 66.6% (low-to-medium gluten intake). The proportion of patients achieving clinical response to biological treatment after 14-16 weeks was compared using logistic regression models. The median gluten intake differed significantly between groups (12.5 g/day vs. 5.9 g/day, standardized mean difference = 1.399). In total, 108 (56%) achieved clinical response to treatment, with no difference between 35 (55%) in the high gluten group and 73 (57%) in the medium-to-low gluten group (OR = 0.96 [0.51-1.79], p = 0.897). No differences were found with secondary outcomes. In conclusion, this study found no association between gluten intake and response to biological treatment in patients with CID.
{"title":"Impact of gluten intake on clinical outcomes in patients with chronic inflammatory diseases initiating biologics: Secondary analysis of the prospective multicentre BELIEVE cohort study.","authors":"Laura Gregersen, Pernille Dyhre Jessen, Helene Wiencke Lund, Silja Hvid Overgaard, Zainab Hikmat, Torkell Ellingsen, Jens Kjeldsen, Andreas Kristian Pedersen, Sofie Ronja Petersen, Mohamad Jawhara, Anders Bathum Nexøe, Anette Bygum, Christian Lodberg Hvas, Jens Frederik Dahlerup, Frederik Olof Bergenheim, Henning Glerup, Rikke Holm Henriksen, Tanja Guldmann, Lone Hvid, Jacob Brodersen, Heidi Lausten Munk, Natalia Pedersen, Sanaz Saboori, Ole Haagen Nielsen, Berit Lillenthal Heitmann, Thorhallur Ingi Haldorsson, Robin Christensen, Vibeke Andersen","doi":"10.1111/sji.13409","DOIUrl":"10.1111/sji.13409","url":null,"abstract":"<p><p>Chronic inflammatory diseases (CIDs) pose a growing healthcare challenge, with a substantial proportion of patients showing inadequate response to biological treatment. There is renewed interest in dietary changes to optimize treatment regimens, with a growing body of evidence suggesting beneficial effects with adherence to a gluten-free diet. This study compared the likelihood of achieving clinical response to biological treatment after 14-16 weeks in patients with CID with high versus low-to-medium gluten intake. Secondary outcomes of interest included changes in disease activity, health-related quality of life and C-reactive protein. The study was a multicentre prospective cohort of 193 participants with a CID diagnosis (i.e. Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis or Psoriasis) who initiated biological treatment between 2017 and 2020. Participants were stratified based on their habitual gluten intake: the upper 33.3% (high gluten intake) and the remaining 66.6% (low-to-medium gluten intake). The proportion of patients achieving clinical response to biological treatment after 14-16 weeks was compared using logistic regression models. The median gluten intake differed significantly between groups (12.5 g/day vs. 5.9 g/day, standardized mean difference = 1.399). In total, 108 (56%) achieved clinical response to treatment, with no difference between 35 (55%) in the high gluten group and 73 (57%) in the medium-to-low gluten group (OR = 0.96 [0.51-1.79], p = 0.897). No differences were found with secondary outcomes. In conclusion, this study found no association between gluten intake and response to biological treatment in patients with CID.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13409"},"PeriodicalIF":4.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}