Pub Date : 2025-05-10DOI: 10.1016/j.clim.2025.110513
Samantha Novotny , Noelle Yoo , Jiaye Chen , Michael Granoth , Anita Kohli-Pamnani , Florence Ida Hsu , Mario Rodenas , Ryan Steele , Kelsey Kaman , Gary Soffer , Christina Price , John K. Kuster , Insoo Kang , Lais Osmani , Junghee J. Shin
Despite advances in genetic testing, Inborn Errors of Immunity (IEI) continue to present a diagnostic challenge, further complicated by genetic variants of uncertain significance (VUS). Therefore, this study evaluated associations of VUS with clinical and immunological characteristics in subjects with potential IEIs. Genes for which VUS were identified were clustered by distinct immune functions. Relationships between gene clusters and clinical and laboratory data were evaluated via SPSS and Python. Both unbiased clustering and manual method classified VUS into six distinct groups based on gene function. Clusters showed association with unique clinical and/or immunological profiles.
{"title":"Association of clinical manifestations and immune alterations with genetic variants of uncertain significance in patients concerned for inborn errors of immunity","authors":"Samantha Novotny , Noelle Yoo , Jiaye Chen , Michael Granoth , Anita Kohli-Pamnani , Florence Ida Hsu , Mario Rodenas , Ryan Steele , Kelsey Kaman , Gary Soffer , Christina Price , John K. Kuster , Insoo Kang , Lais Osmani , Junghee J. Shin","doi":"10.1016/j.clim.2025.110513","DOIUrl":"10.1016/j.clim.2025.110513","url":null,"abstract":"<div><div>Despite advances in genetic testing, Inborn Errors of Immunity (IEI) continue to present a diagnostic challenge, further complicated by genetic variants of uncertain significance (VUS). Therefore, this study evaluated associations of VUS with clinical and immunological characteristics in subjects with potential IEIs. Genes for which VUS were identified were clustered by distinct immune functions. Relationships between gene clusters and clinical and laboratory data were evaluated via SPSS and Python. Both unbiased clustering and manual method classified VUS into six distinct groups based on gene function. Clusters showed association with unique clinical and/or immunological profiles.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"277 ","pages":"Article 110513"},"PeriodicalIF":4.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-05-08DOI: 10.1016/j.clim.2025.110512
Mohammed Ayyad , Walaa Abu Alya , Anas Mufeed Barabrah , Sara Mohammed Darawish , Yazan AlHabil , Majdeddin MohammedAli , Mustafa Zafer Nabilsi , Diya Asad , Laith A. Ayasa , Daniel Matassa
Background
COVID-19 has been linked to autoimmune hemolytic anemia (AIHA), a rare but serious condition causing red blood cell destruction. This systematic review examines the clinical characteristics, management, and outcomes of AIHA in COVID-19 patients.
Methods
A systematic search of PubMed, CINAHL, and Scopus identified 85 studies encompassing 105 patients. Data on demographics, clinical features, and treatment outcomes were extracted.
Results
Of 1402 articles, 85 met inclusion criteria. Most patients were male (54.3 %) with a mean age of 50.6 years, predominantly from Asia (83.5 %). Cold agglutinin AIHA was most common (48.2 %). Presenting symptoms included fatigue, dyspnea, and fever. Steroids were the most effective treatment, used in 95 % of recovered cases. Mortality was 14.3 %, with 26.7 % of deaths directly related to AIHA.
Conclusions
COVID-19 is associated with AIHA, often presenting with non-specific symptoms. Early recognition and prompt steroid therapy are critical for improving outcomes. Further research is needed to guide management.
{"title":"Autoimmune hemolytic anemia in COVID-19 patients: A systematic review of 105 cases on clinical characteristics and outcomes","authors":"Mohammed Ayyad , Walaa Abu Alya , Anas Mufeed Barabrah , Sara Mohammed Darawish , Yazan AlHabil , Majdeddin MohammedAli , Mustafa Zafer Nabilsi , Diya Asad , Laith A. Ayasa , Daniel Matassa","doi":"10.1016/j.clim.2025.110512","DOIUrl":"10.1016/j.clim.2025.110512","url":null,"abstract":"<div><h3>Background</h3><div>COVID-19 has been linked to autoimmune hemolytic anemia (AIHA), a rare but serious condition causing red blood cell destruction. This systematic review examines the clinical characteristics, management, and outcomes of AIHA in COVID-19 patients.</div></div><div><h3>Methods</h3><div>A systematic search of PubMed, CINAHL, and Scopus identified 85 studies encompassing 105 patients. Data on demographics, clinical features, and treatment outcomes were extracted.</div></div><div><h3>Results</h3><div>Of 1402 articles, 85 met inclusion criteria. Most patients were male (54.3 %) with a mean age of 50.6 years, predominantly from Asia (83.5 %). Cold agglutinin AIHA was most common (48.2 %). Presenting symptoms included fatigue, dyspnea, and fever. Steroids were the most effective treatment, used in 95 % of recovered cases. Mortality was 14.3 %, with 26.7 % of deaths directly related to AIHA.</div></div><div><h3>Conclusions</h3><div>COVID-19 is associated with AIHA, often presenting with non-specific symptoms. Early recognition and prompt steroid therapy are critical for improving outcomes. Further research is needed to guide management.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"277 ","pages":"Article 110512"},"PeriodicalIF":4.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-30DOI: 10.1016/j.clim.2025.110510
Megan E. Day-Lewis , Laura Berbert , Michele DeGrazia , Christina Yee , Ari J. Fried , Alan A. Nguyen , Jaime E. Hale , Anne Counihan , Anne Marie Comeau , Elsa R. Treffeisen , Mary Poyner Reed , Craig D. Platt , Janet Chou
Background
Newborn screening for severe combined immunodeficiency (SCID) using T cell receptor excision circles (TRECs) identifies patients with other causes of lymphopenia. The risk of opportunistic infection in patients with non-SCID lymphopenia is poorly understood. We aim to describe incidence and risk factors associated with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection in patients with low TRECs.
Methods
This retrospective study analyzed 289 patients with ≥1 abnormal TREC result.
Results
Nineteen patients had CMV or EBV detected by PCR. Most had resolution of infection (n = 13). Two have chronic viremia, and four expired due to disseminated CMV. Risk factors included undetectable TRECs, consanguinity, family history, low NK, naïve CD4, naïve CD8 cells, and phytohemagglutinin.
Conclusion
Infection with CMV and EBV in patients with low TRECs is rare, however some may benefit from preventative measures. Consideration of risk factors may aid in decision-making and improve outcomes.
{"title":"Incidence and risk factors for CMV and EBV infection in infants with low T-cell receptor excision circles on newborn screen","authors":"Megan E. Day-Lewis , Laura Berbert , Michele DeGrazia , Christina Yee , Ari J. Fried , Alan A. Nguyen , Jaime E. Hale , Anne Counihan , Anne Marie Comeau , Elsa R. Treffeisen , Mary Poyner Reed , Craig D. Platt , Janet Chou","doi":"10.1016/j.clim.2025.110510","DOIUrl":"10.1016/j.clim.2025.110510","url":null,"abstract":"<div><h3>Background</h3><div>Newborn screening for severe combined immunodeficiency (SCID) using T cell receptor excision circles (TRECs) identifies patients with other causes of lymphopenia. The risk of opportunistic infection in patients with non-SCID lymphopenia is poorly understood. We aim to describe incidence and risk factors associated with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection in patients with low TRECs.</div></div><div><h3>Methods</h3><div>This retrospective study analyzed 289 patients with ≥1 abnormal TREC result.</div></div><div><h3>Results</h3><div>Nineteen patients had CMV or EBV detected by PCR. Most had resolution of infection (<em>n</em> = 13). Two have chronic viremia, and four expired due to disseminated CMV. Risk factors included undetectable TRECs, consanguinity, family history, low NK, naïve CD4, naïve CD8 cells, and phytohemagglutinin.</div></div><div><h3>Conclusion</h3><div>Infection with CMV and EBV in patients with low TRECs is rare, however some may benefit from preventative measures. Consideration of risk factors may aid in decision-making and improve outcomes.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"277 ","pages":"Article 110510"},"PeriodicalIF":4.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The COVID-19 pandemic has prompted widespread investigation into its systemic effects, focusing on the consequences of even mild SARS-CoV-2 infections. This study explores the impact of mild COVID-19 on red blood cell (RBC) rheology, specifically deformability and aggregation, both critical for efficient microvascular perfusion and oxygen delivery. Using advanced microfluidic techniques, blood samples from 23 individuals recovering from mild COVID-19 were analyzed and compared to 21 healthy controls. Results revealed significant reductions in RBC deformability and increased aggregation tendencies in the post-COVID group, particularly among females. These rheological changes correlated with fibrinogen and D-dimer levels, suggesting links to systemic inflammation and hypercoagulability. Persistent alterations in RBC functionality may underlie the microvascular dysfunction and symptoms of post-acute COVID-19 syndrome (PACS), including fatigue and cognitive impairment. These findings underscore the need for targeted therapeutic approaches and longitudinal studies to address the hematological dimensions of PACS and improve recovery outcomes.
{"title":"Prolonged alterations in red blood cell rheology following mild SARS-CoV-2 infection: Implications for microvascular health","authors":"Loredana Pazara , Monica Tudorache , Daniela Dusa , Geir Bjørklund , Maryam Dadar , Monica Daniela Doşa , Salvatore Chirumbolo , Claudia Cambrea","doi":"10.1016/j.clim.2025.110511","DOIUrl":"10.1016/j.clim.2025.110511","url":null,"abstract":"<div><div>The COVID-19 pandemic has prompted widespread investigation into its systemic effects, focusing on the consequences of even mild SARS-CoV-2 infections. This study explores the impact of mild COVID-19 on red blood cell (RBC) rheology, specifically deformability and aggregation, both critical for efficient microvascular perfusion and oxygen delivery. Using advanced microfluidic techniques, blood samples from 23 individuals recovering from mild COVID-19 were analyzed and compared to 21 healthy controls. Results revealed significant reductions in RBC deformability and increased aggregation tendencies in the post-COVID group, particularly among females. These rheological changes correlated with fibrinogen and D-dimer levels, suggesting links to systemic inflammation and hypercoagulability. Persistent alterations in RBC functionality may underlie the microvascular dysfunction and symptoms of post-acute COVID-19 syndrome (PACS), including fatigue and cognitive impairment. These findings underscore the need for targeted therapeutic approaches and longitudinal studies to address the hematological dimensions of PACS and improve recovery outcomes.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"277 ","pages":"Article 110511"},"PeriodicalIF":4.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study explores immune responses in mild Omicron-era COVID-19 breakthrough cases, focusing on cytokine dysregulation, antibody dynamics, and Long COVID. We analyzed samples from 114 mild symptomatic COVID-19 patients across multiple pandemic waves, each dominated by different SARS-CoV-2 variants, at three timepoints: (T1: 2–4 weeks, T2: 3–4 months, T3: 6–8 months post-infection). Persistent IP-10 elevation up to 8 months post–Omicron breakthrough infection suggests sustained low-grade immune activation that appears unique to this wave. Hybrid immunity from Omicron breakthrough infections elicited broad cross-variant antibody recognition but showed declining neutralization over time. Among vaccination regimens, mRNA-inclusive combinations were associated with lower Long COVID scores. CoV-229E antibody levels correlated with Long COVID scores. These findings underscore the need for extended monitoring of even mild COVID-19 cases and highlight the potential of mRNA vaccines in reducing post-COVID-19 complications. Insights into post-infection immune alterations and vaccine effects can inform the development of future vaccination strategies and approaches for managing post-COVID-19 conditions.
{"title":"Persistent IP-10/CXCL10 dysregulation following mild Omicron breakthrough infection: Immune network signatures across COVID-19 waves and implications for mRNA vaccine outcomes","authors":"Vimvara Vacharathit , Mutita Pluempreecha , Suwimon Manopwisedjaroen , Chanya Srisaowakarn , Sirawat Srichatrapimuk , Paskorn Sritipsukho , Naiyana Sritipsukho , Arunee Thitithanyanont","doi":"10.1016/j.clim.2025.110507","DOIUrl":"10.1016/j.clim.2025.110507","url":null,"abstract":"<div><div>This study explores immune responses in mild Omicron-era COVID-19 breakthrough cases, focusing on cytokine dysregulation, antibody dynamics, and Long COVID. We analyzed samples from 114 mild symptomatic COVID-19 patients across multiple pandemic waves, each dominated by different SARS-CoV-2 variants, at three timepoints: (T1: 2–4 weeks, T2: 3–4 months, T3: 6–8 months post-infection). Persistent IP-10 elevation up to 8 months post–Omicron breakthrough infection suggests sustained low-grade immune activation that appears unique to this wave. Hybrid immunity from Omicron breakthrough infections elicited broad cross-variant antibody recognition but showed declining neutralization over time. Among vaccination regimens, mRNA-inclusive combinations were associated with lower Long COVID scores. CoV-229E antibody levels correlated with Long COVID scores. These findings underscore the need for extended monitoring of even mild COVID-19 cases and highlight the potential of mRNA vaccines in reducing post-COVID-19 complications. Insights into post-infection immune alterations and vaccine effects can inform the development of future vaccination strategies and approaches for managing post-COVID-19 conditions.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"278 ","pages":"Article 110507"},"PeriodicalIF":4.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-26DOI: 10.1016/j.clim.2025.110503
Ravindra Daddali , Kaisa Kettunen , Tanja Turunen , Ainsley V.C. Knox , Pia Laine , Iftekhar Chowdhury , Markku Vänttinen , Nanni Mamia , Amy L. Stiegler , Titus J. Boggon , Juha Kere , Neil Romberg , Mikko R.J. Seppänen , Markku Varjosalo , Timi Martelius , Juha Grönholm
PU.1 is an Ets family transcription factor crucial for hematopoietic cell fate. Complete PU.1 deficiency lethally arrests lympho- and myelopoiesis in mice. Individuals with SPI1 heterozygous loss-of-function variants exhibit disrupted gene expression patterns associated with B cell development. We identified the vertical transmission of a heterozygous SPI1c.538C>T p.(L180F) variant in a Finnish family. The index patient and his mother had severe bacterial infections, agammaglobulinemia, and low myeloid and plasmacytoid dendritic cell counts. The variant carrier sister had slightly reduced B cell counts, isolated IgA deficiency, and reduced dendritic cell counts. All individuals had diminished PU.1 protein expression in monocytes. In vitro studies showed that PU.1 L180F variant is less expressed and predominantly located in the cytoplasm. PU.1 WT mainly interacts with chromatin and centrosome-associated proteins, while the L180F variant showed fewer interactions. Our findings describe a novel PU.1 variant leading to agammaglobulinemia with variable penetrance.
{"title":"Novel heterozygous SPI1c.538C>T p.(Leu180Phe) variant causes PU.1 haploinsufficiency leading to agammaglobulinemia","authors":"Ravindra Daddali , Kaisa Kettunen , Tanja Turunen , Ainsley V.C. Knox , Pia Laine , Iftekhar Chowdhury , Markku Vänttinen , Nanni Mamia , Amy L. Stiegler , Titus J. Boggon , Juha Kere , Neil Romberg , Mikko R.J. Seppänen , Markku Varjosalo , Timi Martelius , Juha Grönholm","doi":"10.1016/j.clim.2025.110503","DOIUrl":"10.1016/j.clim.2025.110503","url":null,"abstract":"<div><div>PU.1 is an Ets family transcription factor crucial for hematopoietic cell fate. Complete PU.1 deficiency lethally arrests lympho- and myelopoiesis in mice. Individuals with <em>SPI1</em> heterozygous loss-of-function variants exhibit disrupted gene expression patterns associated with B cell development. We identified the vertical transmission of a heterozygous <em>SPI1</em>c.538C>T p.(L180F) variant in a Finnish family. The index patient and his mother had severe bacterial infections, agammaglobulinemia, and low myeloid and plasmacytoid dendritic cell counts. The variant carrier sister had slightly reduced B cell counts, isolated IgA deficiency, and reduced dendritic cell counts. All individuals had diminished PU.1 protein expression in monocytes. <em>In vitro</em> studies showed that PU.1 L180F variant is less expressed and predominantly located in the cytoplasm. PU.1 WT mainly interacts with chromatin and centrosome-associated proteins, while the L180F variant showed fewer interactions. Our findings describe a novel PU.1 variant leading to agammaglobulinemia with variable penetrance.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"277 ","pages":"Article 110503"},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-26DOI: 10.1016/j.clim.2025.110508
Yuan Xue, Yi Guo, Min Cheng, Xiujuan Li, Siqi Hong, Li Jiang, Wei Han
An 11-year-old male patient presented with acute neurological deterioration, including meningitis, encephalitis, and myelitis. Initial testing detected antibody against metabotropic glutamate receptor 2 (mGluR2-Ab); retesting identified coexisting anti-glial fibrillary acidic protein antibody (GFAP-Ab). Pathogenic examinations were negative. The patient received a combination of immunotherapies, including intravenous methylprednisolone pulse therapy, human immunoglobulin pulse therapy, and plasma exchange. Five months after onset, the patient showed a favorable prognosis, though a residual neurogenic bladder remained. We present the first documented case of overlapping autoimmune syndrome with concurrent mGluR2-Ab and GFAP-Ab. The coexistence of these antibodies can lead to a wide range of clinical manifestations, including simultaneous GFAP-Ab-related meningoencephalomyelitis and mGluR2-Ab-related ataxia. This complexity complicates diagnosis and treatment, underscoring the need for a comprehensive understanding of the pathogenic mechanisms of these antibodies and timely combined immunotherapy. Additionally, this case suggests that mGluR2-Ab and GFAP-Ab may serve as the jointly responsible antibodies for this condition.
{"title":"Overlapping syndrome with concomitant mGluR2-Ab and GFAP-Ab: A case report","authors":"Yuan Xue, Yi Guo, Min Cheng, Xiujuan Li, Siqi Hong, Li Jiang, Wei Han","doi":"10.1016/j.clim.2025.110508","DOIUrl":"10.1016/j.clim.2025.110508","url":null,"abstract":"<div><div>An 11-year-old male patient presented with acute neurological deterioration, including meningitis, encephalitis, and myelitis. Initial testing detected antibody against metabotropic glutamate receptor 2 (mGluR2-Ab); retesting identified coexisting anti-glial fibrillary acidic protein antibody (GFAP-Ab). Pathogenic examinations were negative. The patient received a combination of immunotherapies, including intravenous methylprednisolone pulse therapy, human immunoglobulin pulse therapy, and plasma exchange. Five months after onset, the patient showed a favorable prognosis, though a residual neurogenic bladder remained. We present the first documented case of overlapping autoimmune syndrome with concurrent mGluR2-Ab and GFAP-Ab. The coexistence of these antibodies can lead to a wide range of clinical manifestations, including simultaneous GFAP-Ab-related meningoencephalomyelitis and mGluR2-Ab-related ataxia. This complexity complicates diagnosis and treatment, underscoring the need for a comprehensive understanding of the pathogenic mechanisms of these antibodies and timely combined immunotherapy. Additionally, this case suggests that mGluR2-Ab and GFAP-Ab may serve as the jointly responsible antibodies for this condition.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"277 ","pages":"Article 110508"},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-25DOI: 10.1016/j.clim.2025.110494
Yidong Tan , Xuanyi Chen , Yihang Shen , Jinxiang Yang , Bing Wang , Yumeng Wang , Weinan Zhou , Qiuyi Han , Zhirong Yao , Huaguo Li , Jianying Liang
Epidermolytic ichthyosis (EI) is a genetic skin disorder caused by mutations in the KRT1 and KRT10 genes, leading to severe skin abnormalities and inflammation. Current treatment options are limited, emphasizing the need for pathogenesis-based therapies. This study investigates the role of T helper type 17 (TH17) inflammatory responses in EI and explores the mechanisms underlying these responses. We found that patients from the family carrying both KRT1 and MPO mutations exhibited varying degrees of psoriasis-like manifestations and significant therapeutic responses to anti-IL-17 A treatment. The treatment efficacy was also confirmed in patients with KRT10 mutations. Mechanistically, Single-nucleus RNA sequencing revealed significantly elevated levels of TH-17 related cytokines in epidermis and CCR6+ TH17 cell infiltration in the dermis. Additionally, we observed aberrant activation of the IκBα–JNK–c-Jun signaling pathway, leading to heightened IL-8 expression and exacerbated inflammation. Our findings underscore the critical role of TH17-mediated inflammation in the pathogenesis of EI and suggest potential therapeutic avenues targeting this pathway to improve patient outcomes.
{"title":"Exploring TH17-mediated inflammation in epidermolytic ichthyosis: Clinical and mechanistic insight","authors":"Yidong Tan , Xuanyi Chen , Yihang Shen , Jinxiang Yang , Bing Wang , Yumeng Wang , Weinan Zhou , Qiuyi Han , Zhirong Yao , Huaguo Li , Jianying Liang","doi":"10.1016/j.clim.2025.110494","DOIUrl":"10.1016/j.clim.2025.110494","url":null,"abstract":"<div><div>Epidermolytic ichthyosis (EI) is a genetic skin disorder caused by mutations in the <em>KRT1</em> and <em>KRT10</em> genes, leading to severe skin abnormalities and inflammation. Current treatment options are limited, emphasizing the need for pathogenesis-based therapies. This study investigates the role of T helper type 17 (T<sub>H</sub>17) inflammatory responses in EI and explores the mechanisms underlying these responses. We found that patients from the family carrying both <em>KRT1</em> and <em>MPO</em> mutations exhibited varying degrees of psoriasis-like manifestations and significant therapeutic responses to anti-IL-17 A treatment. The treatment efficacy was also confirmed in patients with <em>KRT10</em> mutations. Mechanistically, Single-nucleus RNA sequencing revealed significantly elevated levels of T<sub>H</sub>-17 related cytokines in epidermis and CCR6<sup>+</sup> TH17 cell infiltration in the dermis. Additionally, we observed aberrant activation of the IκBα–JNK–c-Jun signaling pathway, leading to heightened IL-8 expression and exacerbated inflammation. Our findings underscore the critical role of T<sub>H</sub>17-mediated inflammation in the pathogenesis of EI and suggest potential therapeutic avenues targeting this pathway to improve patient outcomes.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"277 ","pages":"Article 110494"},"PeriodicalIF":4.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-25DOI: 10.1016/j.clim.2025.110506
Minjin Wang , Jierui Wang , Jianzhao Zhai , Yangyi He , Yuwen Ma , Zhiyin Wang , Yan Ren , Binwu Ying , Dong Zhou , Jinmei Li
Background
N-methyl-d-aspartate receptor encephalitis (NMDAR-E) is a severe autoimmune disorder characterized by neuropsychiatric symptoms and immune dysregulation ，involves T-cell dysregulation, but specific T-cell subset roles remain unclear. This study analyzed peripheral blood T-cell subsets as biomarkers for monitoring and severity prediction.
Methods
Peripheral blood samples from 32 NMDAR-E patients, 31 antibody-mediated encephalitis, 26 viral encephalitis patients, and 23 healthy controls were analyzed using flow cytometry. Key markers of T-cell activation and co-stimulation were assessed. Clinical outcomes were correlated with immune profiles to develop a predictive model.
Results
NMDAR-E patients showed elevated CD4+ T-cell activation, with increased CD28, CD38, and HLA-DR expression versus controls, indicating immune hyperactivation with compensatory regulation. The T-cell-based model predicted severe cases with high accuracy (AUC = 0.91).
Conclusion
CD4+ T-cell activation is central to NMDAR-E pathogenesis, highlighting diagnostic/therapeutic potential. Future studies must validate the model in larger cohorts and address peripheral blood analysis limitations.
n -甲基-d-天冬氨酸受体脑炎（NMDAR-E）是一种以神经精神症状和免疫失调为特征的严重自身免疫性疾病，涉及t细胞失调，但具体的t细胞亚群作用尚不清楚。本研究分析了外周血t细胞亚群作为监测和严重程度预测的生物标志物。方法采用流式细胞术对32例NMDAR-E患者、31例抗体介导性脑炎患者、26例病毒性脑炎患者和23例健康对照者的外周血进行分析。评估t细胞活化和共刺激的关键标志物。临床结果与免疫特征相关，以建立预测模型。结果与对照组相比，snmdar - e患者CD4+ t细胞活化升高，CD28、CD38和HLA-DR表达增加，表明免疫过度激活具有代偿性调节。基于t细胞的模型预测重症病例准确率高（AUC = 0.91）。结论cd4 + t细胞活化是NMDAR-E发病机制的核心，具有重要的诊断/治疗潜力。未来的研究必须在更大的队列中验证该模型，并解决外周血分析的局限性。
{"title":"Peripheral T-cell subset activation in NMDAR encephalitis: Insights into pathogenesis and biomarker potential for disease monitoring","authors":"Minjin Wang , Jierui Wang , Jianzhao Zhai , Yangyi He , Yuwen Ma , Zhiyin Wang , Yan Ren , Binwu Ying , Dong Zhou , Jinmei Li","doi":"10.1016/j.clim.2025.110506","DOIUrl":"10.1016/j.clim.2025.110506","url":null,"abstract":"<div><h3>Background</h3><div><em>N</em>-methyl-<span>d</span>-aspartate receptor encephalitis (NMDAR-E) is a severe autoimmune disorder characterized by neuropsychiatric symptoms and immune dysregulation ，involves T-cell dysregulation, but specific T-cell subset roles remain unclear. This study analyzed peripheral blood T-cell subsets as biomarkers for monitoring and severity prediction.</div></div><div><h3>Methods</h3><div>Peripheral blood samples from 32 NMDAR-E patients, 31 antibody-mediated encephalitis, 26 viral encephalitis patients, and 23 healthy controls were analyzed using flow cytometry. Key markers of T-cell activation and co-stimulation were assessed. Clinical outcomes were correlated with immune profiles to develop a predictive model.</div></div><div><h3>Results</h3><div>NMDAR-E patients showed elevated CD4+ T-cell activation, with increased CD28, CD38, and HLA-DR expression versus controls, indicating immune hyperactivation with compensatory regulation. The T-cell-based model predicted severe cases with high accuracy (AUC = 0.91).</div></div><div><h3>Conclusion</h3><div>CD4+ T-cell activation is central to NMDAR-E pathogenesis, highlighting diagnostic/therapeutic potential. Future studies must validate the model in larger cohorts and address peripheral blood analysis limitations.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"277 ","pages":"Article 110506"},"PeriodicalIF":4.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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