Journal of Clinical Immunology最新文献

{"title":"Deciphering B cell Maturation Dynamics in Hyper-IgM Syndromes.","authors":"Hande Üçler Çınar, Murat Cansever, Şerife Erdem, Abdullah Arık, Ahmet Eken","doi":"10.1007/s10875-026-02046-6","DOIUrl":"10.1007/s10875-026-02046-6","url":null,"abstract":"<p><strong>Purpose: </strong>Hyper-IgM syndromes (HIGM) are primary immunodeficiencies characterized by defective class-switch recombination (CSR) and impaired humoral immunity. While genetic causes such as CD40L and AICDA mutations are well established, a detailed comparison of B cell maturation dynamics across HIGM subtypes remains limited. To comprehensively characterize B cell immunophenotypes and functional responses in patients with HIGM and to delineate mutation-specific differences in B cell maturation and proliferation.</p><p><strong>Method: </strong>Four patients with genetically confirmed HIGM (one CD40L and three homozygous AICDA mutations, c.70C>T; p.R24W) and age- and sex-matched healthy controls were studied. Peripheral blood mononuclear cells were analyzed by multiparameter flow cytometry to define B cell subsets based on CD19, CD20, CD24, CD27, CD38, IgD, and IgM expression. B cell proliferation was assessed following CpG stimulation.</p><p><strong>Results: </strong>All patients exhibited a marked reduction of class-switched memory B cells (CD27⁺IgD⁻) and accumulation of naive B cells (CD27⁻IgD⁺), consistent with defective CSR. The CD40L-deficient patient demonstrated profound depletion of plasmablasts and precursor skewing, reflecting failure of germinal center formation. In contrast, AID patients showed preserved CD27 expression with variable expansion of transitional and plasmablast populations, suggesting intact T cell-dependent activation but intrinsic failure of CSR. Functional assays revealed heterogeneous proliferative responses in CD40L deficiency and AICDA-deficient patient, but impaired proliferation in another AICDA-deficient individual, highlighting inter-individual variability.</p><p><strong>Conclusion: </strong>Detailed immunophenotyping reveals distinct B cell maturation arrest points in CD40L- versus AICDA-associated HIGM. Flow cytometric analysis of B cell subsets provides valuable insights into disease mechanisms, supports differential diagnosis, and may inform clinical monitoring and therapeutic decision-making in HIGM.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bronchiectasis in Inborn Errors of Immunity: Prevalence, Predictors, and Cardiopulmonary Complications in a Genetically Characterized Cohort.","authors":"Diana Marangu-Boore, Katherine Myint-Hpu, Esther Kang, Luigi D Notarangelo, Ottavia M Delmonte","doi":"10.1007/s10875-026-02044-8","DOIUrl":"10.1007/s10875-026-02044-8","url":null,"abstract":"<p><strong>Purpose: </strong>Bronchiectasis poses a serious but incompletely defined burden in patients with inborn errors of immunity (IEI). We determined its prevalence, independent predictors, and cardiopulmonary complications in a genetically characterized IEI cohort to inform care in this vulnerable population.</p><p><strong>Methods: </strong>We conducted a cross-sectional analysis of patients enrolled in a National Institutes of Health prospective IEI protocol (2018-2024) who had undergone whole exome or genome sequencing and chest computed tomography (CT). Bronchiectasis was radiologically confirmed, excluding traction bronchiectasis. Predictors were identified by multivariable logistic regression. Cardiopulmonary outcomes included spirometry, lung volumes, diffusing capacity, six-minute walk distance, pulmonary hypertension by echocardiography, and mortality.</p><p><strong>Results: </strong>Of 229 enrolled patients, 131 were eligible, representing 31 distinct IEIs. Median age at first chest CT was 20 years (IQR 10-33). The most common CT finding was pulmonary nodules (55%). Bronchiectasis prevalence was 27% (95% CI 20-35%). Independent predictors were older age at first CT (aOR 1.04, 95% CI 1.01-1.08), combined immunodeficiency affecting cellular and humoral immunity (aOR 4.30, 95% CI 1.42-14.54), predominantly antibody deficiencies (aOR 5.83, 95% CI 1.66-22.26), and diseases of immune dysregulation (aOR 7.56, 95% CI 1.07-52.72). Patients with bronchiectasis had greater cardiopulmonary impairment across all measured domains and higher mortality (15% vs. 3%; P = 0.046).</p><p><strong>Conclusions: </strong>Bronchiectasis is common across IEI diagnostic classes and carries substantial cardiopulmonary morbidity and excess mortality. Older age at first chest CT and specific IUIS classes, particularly predominantly antibody deficiencies and diseases of immune dysregulation, independently predict bronchiectasis, identifying patients who would benefit most from early pulmonary surveillance.</p><p><strong>Trial protocol: </strong>NCT03394053.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult-Onset LRBA Deficiency Presenting with Rheumatoid Arthritis-Like Manifestations: A Case Report.","authors":"Keita Ninagawa, Yuki Kudo, Michihito Kono, Ryo Hisada, Tatsuya Atsumi","doi":"10.1007/s10875-026-02048-4","DOIUrl":"10.1007/s10875-026-02048-4","url":null,"abstract":"<p><p>Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency is a primary inborn error of immunity characterized by immune dysregulation and frequently associated with autoimmune connective tissue manifestations. We describe an adult woman diagnosed with rheumatoid arthritis who was subsequently found to have LRBA deficiency based on genetic testing and investigated inflammatory proteins potentially involved in the pathogenesis of LRBA deficiency. A 44-year-old woman with rheumatoid arthritis presented with persistent diarrhea and abdominal distention lasting over eight months. Abdominal imaging revealed intestinal pseudo-obstruction. Her medical history included megaloblastic anemia, type 1 diabetes, and chronic thyroiditis since childhood. Her brother had died of unexplained diarrhea during childhood. Given her multiple autoimmune manifestations and family history, a primary immune deficiency (PID) was suspected. Genetic analysis identified a heterozygous LRBA splice-site variant (c.1162-1G > A) and a possible heterozygous deletion involving exons 18-41, suggesting compound heterozygous LRBA variants. Thus, the diagnosis of LRBA deficiency-associated autoimmunity. Following the diagnosis, she was treated with abatacept, a CTLA4-immunoglobulin fusion protein, resulting in improvement of gastrointestinal symptoms. Proximity extension assay (Olink^® Target) revealed marked decreases in serum interleukin-17 A (from 3.36 to 2.22 normalized protein expression), tumor necrosis factor (3.26 to 0.69), and chemokine (C-C motif) ligand 20 (3.14 to 0.84) after treatment. LRBA deficiency is characterized by an imbalance of CD4⁺ T cells with increased Th1 and Th17 populations and reduced regulatory T cells. This case highlights that patients with PID, including LRBA deficiency, can present with autoimmune manifestations, and abatacept may represent an effective targeted treatment option for LRBA-deficiency.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"46 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunopathological Profile of Patients with Thymic Epithelial Tumour and Good Syndrome in Advanced Stage.","authors":"Fabiana Napolitano, Erica Pietroluongo, Michele Francesco Di Tolla, Margaret Ottaviano, Vittoria D'Esposito, Pietro De Placido, Alberto Servetto, Giuseppe Portella, Roberto Bianco, Giovannella Palmieri, Pietro Formisano, Anna Maria Malfitano","doi":"10.1007/s10875-026-02050-w","DOIUrl":"10.1007/s10875-026-02050-w","url":null,"abstract":"<p><strong>Purpose: </strong>Thymic epithelial tumors (TETs) are associated with Good Syndrome (GS), a secondary immunodeficiency characterized by hypogammaglobulinemia, B-cell lymphopenia, and recurrent infections. This study investigated the immunological profile of TET patients to identify immune alterations associated with GS, independently of autoimmune diseases (AD) and disease stage.</p><p><strong>Methods: </strong>Seventy patients with TETs were stratified according to GS status (GS+/GS-), AD status (AD+/AD-), and disease stage (advanced disease, IVA/B, or no evidence of disease, NED). Serum immunoglobulins, peripheral immune cell subsets, and circulating cytokines, chemokines, growth factors, and metabolic markers were evaluated.</p><p><strong>Results: </strong>GS+ patients showed reduced IgM and IgG levels compared with GS- patients; however, after stratification, only IgM remained reduced in GS+AD- NED patients. Peripheral B-cell lymphopenia was consistently observed in GS+ patients across both disease stages, independently of AD status. Treg frequencies increased in GS- patients with advanced disease and in GS+AD+ NED patients. Monocytopenia and an inverted CD4+/CD8+ ratio were mainly observed in GS+AD+ patients with advanced disease. Cytokine profiling identified increased levels of IL-1β, IL-10, IL-17, TNFα, IFN-γ, IL-4, IL-5, IL-6, Eotaxin, G-CSF, and IP-10 in GS+ patients. Among these, IP-10 remained consistently elevated regardless of disease stage or AD status.</p><p><strong>Conclusion: </strong>Peripheral B-cell lymphopenia and elevated IP-10 levels represent the most consistent immunological features associated with GS, independent of disease stage and AD status, whereas serum immunoglobulin levels appear less reliable in advanced disease. These findings support the diagnostic value of immunophenotyping, particularly B-cell quantification and IP-10 measurement, for identifying GS in patients with TETs.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facial Dysmorphism and Severe Vascular Phenotype in TRNT1 Deficiency with Concomitant Antithrombin III Deficiency.","authors":"David M Matea, Smaranda T Arghirescu, Adela Chirita-Emandi, Patricia Urtila, Mihaela Bataneant","doi":"10.1007/s10875-026-02047-5","DOIUrl":"10.1007/s10875-026-02047-5","url":null,"abstract":"<p><p>TRNT1 deficiency (SIFD syndrome) is a rare inborn error of immunity characterized by sideroblastic anemia, immunodeficiency, periodic fevers, and developmental delay. We report two Romanian patients with genetically confirmed TRNT1 deficiency presenting with characteristic hematologic and immunologic abnormalities and a distinctive facial dysmorphism. One patient additionally developed severe gastrointestinal ischemia and intracranial hemorrhage in the setting of concomitant hereditary antithrombin III deficiency. These observations expand the phenotypic spectrum associated with TRNT1 deficiency and highlight the marked clinical variability of this disorder. The contribution of TRNT1-associated inflammation to the vascular phenotype remains speculative and cannot be distinguished from the effects of the concomitant thrombophilic condition.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intersection Between Systemic Autoimmune Diseases, Primary Immunodeficiency and Cancer: a Field in its Infancy.","authors":"Silvia Sánchez-Ramón, Ana Isabel Ramos-Lisbona, Mohammed Yousuf Karim","doi":"10.1007/s10875-026-02030-0","DOIUrl":"10.1007/s10875-026-02030-0","url":null,"abstract":"<p><strong>Purpose: </strong>Systemic autoimmune diseases and primary immunodeficiencies/inborn errors of immunity (PIDs/IEIs) have traditionally been viewed as opposing immunological entities. However, growing genetic, immunological, and clinical evidence challenges this dichotomy, revealing a shared spectrum of immune dysregulation, genetic vulnerability, and convergent phenotypes. Advances in next-generation sequencing have identified monogenic IEIs presenting with autoimmune manifestations indistinguishable from polygenic systemic autoimmune diseases, blurring diagnostic boundaries and carrying therapeutic implications. This review aims to explore the relationships between autoimmunity, immunodeficiency, and malignancy, emphasizing how immune dysregulation underlies susceptibility to infections, cancer, and treatment-related complications.</p><p><strong>Methods: </strong>We performed a narrative review of the literature with a focus on underlying mechanisms, clinical manifestations, and implications for diagnosis and management.</p><p><strong>Results: </strong>Immune dysregulation underlies susceptibility to infections, cancer, and treatment-related complications. Immunosuppressive and biologic/targeted therapies remain cornerstone treatments but entail risks, including serious and opportunistic infections, organ toxicity, and malignancy, particularly when underlying PIDs/IEIs remain unrecognized. Failure to recognize underlying PID/IEI in patients with early-onset, refractory, syndromic, or otherwise atypical autoimmune disease leads to misdiagnosis and harmful therapeutic escalation, underscoring the need for prompt immunological screening. Immunological screening, including immunoglobulin profiling, lymphocyte subsets, and genetic testing, may improve diagnostic accuracy and guide treatment strategies. Malignancy represents an intersection point, with disease-specific cancer patterns reflecting distinct pathogenic mechanisms across autoimmune diseases and IEIs, highlighting the clinical relevance of disease-specific cancer risk stratification and surveillance.</p><p><strong>Conclusion: </strong>Integrating mechanistic insights and genetic profiling may enable a precision medicine approach that optimizes efficacy while minimizing harm across this expanding immunological continuum.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148329971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disseminated Tuberculosis and Early-Onset SLE in a Child with a Novel STAT1 Gain-of-Function Mutation: a Case Report.","authors":"Serkan Arslan, Ahmet Sert, Meryem Özçelik, Safa Barış, Çiğdem Aydoğmuş, Özge Kaba, Burcu Çil Yılmaz, Simge Erdil, Kübra Yırgın, Pınar Gökmirza, Mehmet Cihangir Çatak","doi":"10.1007/s10875-026-02040-y","DOIUrl":"10.1007/s10875-026-02040-y","url":null,"abstract":"<p><strong>Background: </strong>Gain-of-function (GOF) mutations in the STAT1 gene result in heightened interferon signaling and impaired IL-17 immunity. While chronic mucocutaneous candidiasis (CMC) remains the hallmark feature, affected individuals often display a broader phenotype including viral infections, mycobacterial susceptibility, and autoimmune diseases.</p><p><strong>Case presentation: </strong>We describe a 4-year-old girl who initially presented with abdominal pain and was diagnosed with acute appendicitis. During surgery, marked mesenteric lymphadenopathy was discovered, and histopathology revealed acid-fast bacilli. Mycobacterium tuberculosis was confirmed by gastric fluid PCR, prompting initiation of anti-tuberculosis therapy. Her past medical history included hospitalization for herpes zoster and recurrent episodes of oral candidiasis during febrile illnesses. Immunologic evaluation showed normal immunoglobulin levels, vaccine responses, oxidative burst, and lymphocyte proliferation. However, low NK cells, reduced recent thymic emigrants, and decreased class-switched memory B cells were noted. Genetic testing revealed a previously unreported heterozygous STAT1 variant (p.Thr387Arg), classified as likely pathogenic according to ACMG criteria with a CADD score of 23.4. Parental genetic testing was negative, suggesting a de novo mutation. Although STAT1 phosphorylation could not be assessed, the proportion of IL-17-producing CD4⁺ T cells was markedly reduced, supporting impaired Th17 immunity. Based on clinical, immunologic, and genetic findings, a clinical and immunological phenotype consistent with STAT1 GOF was established. One year later, the patient developed arthritis and was diagnosed with systemic lupus erythematosus (SLE) based on autoantibody positivity and low complement levels. During follow-up, she also developed hemophagocytic lymphohistiocytosis (HLH), further reflecting severe immune dysregulation. Ruxolitinib was initiated as bridging therapy, resulting in partial clinical improvement, and hematopoietic stem cell transplantation (HSCT) was planned as definitive therapy.</p><p><strong>Conclusion: </strong>This report describes a novel STAT1 variant consistent with a gain-of-function phenotype associated with disseminated tuberculosis and early-onset SLE, expanding the clinical and molecular spectrum of this disorder. In children presenting with overlapping infectious and autoimmune features, underlying inborn errors of immunity should be considered.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"46 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humoral Immune Abnormalities in Transient Childhood Neutropenia: Insights From a 10-year Cohort Study in a Tertiary Center.","authors":"Emmanuele Schorn, Maarja Soomann, Seraina Prader, Jana Pachlopnik Schmid, Johannes Trück","doi":"10.1007/s10875-026-02042-w","DOIUrl":"10.1007/s10875-026-02042-w","url":null,"abstract":"<p><strong>Purpose: </strong>Transient neutropenia in early childhood is a relatively common condition often associated with neutrophil-specific autoantibodies; however, its connection to broader humoral immune system abnormalities remains poorly understood.</p><p><strong>Methods: </strong>The current study investigated this relationship through a retrospective cohort analysis at a pediatric tertiary center in Switzerland.</p><p><strong>Results: </strong>In total, 92 children aged 0 to 6 years seen at our hospital between January 2014 and December 2023 were included in the final cohort. Of the 68 children who underwent detailed immunological testing, 52 (77%) exhibited humoral abnormalities, with 24 (35%) classified as moderate and 28 (41%) as mild. Patients with humoral abnormalities exhibited neutrophil-specific autoantibodies less commonly (56% vs. 100%, p = 0.003), had higher minimum absolute neutrophil counts (ANC) (median minimum ANC 0.26 vs. 0.05 × 10⁹/L, p = 0.002), and a shorter duration of neutropenia (median duration 12.1 vs. 28.5 months, p = 0.001) compared to patients without abnormalities. Additionally, 36% of patients with humoral abnormalities had inadequate vaccine antibodies, compared to none in the group without abnormalities. These findings suggest that patients with humoral abnormalities may have a higher risk of infection and could benefit from additional counseling and timely booster vaccinations.</p><p><strong>Conclusion: </strong>This study highlights a potential causal relationship between humoral immune system abnormalities and transient neutropenia in early childhood. Routine immunological assessments in children with early-onset (autoimmune) neutropenia are likely to aid in patient management and family counseling.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Whole Genome Sequencing in 25 Families with Suspected Inborn Errors of Immunity: Diagnostic Yield and Clinical Relevance of Genome-wide Analysis.","authors":"Jong Kwon Lee, Ja-Hyun Jang, Doo Ri Kim, Areum Shin, Jong-Ho Park, Young-Gon Kim, Jong-Won Kim, Yae-Jean Kim, Eun-Suk Kang","doi":"10.1007/s10875-026-02043-9","DOIUrl":"10.1007/s10875-026-02043-9","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"46 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13269311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Review and Meta-analysis of Anti-interferon Auto-antibodies in Infectious Diseases.","authors":"Robert Hill, Akish Luintel, Ernest Mutengesa, Douglas L Fink","doi":"10.1007/s10875-026-02038-6","DOIUrl":"10.1007/s10875-026-02038-6","url":null,"abstract":"<p><strong>Purpose: </strong>To perform a systematic review and meta-analysis of prevalence and function of anti-interferon auto-antibodies in acute infectious diseases.</p><p><strong>Methods: </strong>We performed a search on the following electronic bibliographic databases: Medline, Embase, Web of Science and Cochrane. Eligible studies generated a systematic review and random effects model meta-analysis of pooled seroprevalence and neutralisation status of anti-interferon auto-antibodies in acute infectious diseases.</p><p><strong>Results: </strong>Thirty-seven studies including 12,629 individuals with SARS-CoV-2 infection were analysed. There are insufficient data for meta-analyses of auto-antibodies in non-SARS-CoV-2 infectious diseases, with crude seroprevalence of auto-antibodies varying widely (0.0-77.0%). The pooled seroprevalence of anti-IFNɑ and/or anti-IFN⍵ auto-antibodies in individuals with SARS-CoV-2 infection was 14% (95%CI 9-18%, I² = 92%, [Formula: see text]² = 0.0151, p < 0.01). Pooled prevalence of neutralising auto-antibodies were slightly lower (12%; 95%CI 8-17%, I² = 77%, [Formula: see text]² = 0.0027, p < 0.01). The high heterogeneity may reflect divergent SARS-CoV-2 disease severity across studies, and methodological diversity for measurement and definition of auto-antibody binding and neutralisation. Pooled seroprevalence for anti-IFNɑ auto-antibodies in uninfected healthy controls were < 1% (95%CI 0-1%, I² = 90%, [Formula: see text]² = 0.0028, p < 0.01).</p><p><strong>Conclusion: </strong>Anti-interferon auto-antibodies may impair immune responses to diverse infections leading to life-threatening disease. These auto-antibodies have not been studied at all in most infectious diseases, most notably for bacterial infection. This study illustrates the urgent need to standardise methodology and reporting of auto-antibodies in the setting of infectious diseases so that the immunopathology and translational impact of these novel biomarkers can be realised.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}