J Clin Immunol. 2026 Jul 18. doi: 10.1007/s10875-026-02049-3. Online ahead of print. ABSTRACT PURPOSE: Hepatic actinomycosis is a rare granulomatous disease caused by an opportunistic Gram-positive bacillus of the genus Actinomyces. We report an unusual association between hepatic actinomycosis and IgG-4 related disease. CASE DESCRIPTION: A 70-year-old man was admitted to the University Hospital of … Read more
J Clin Immunol. 2026 Jul 11. doi: 10.1007/s10875-026-02051-9. Online ahead of print. ABSTRACT NFKB2 encodes the precursor p100 which undergoes processing to generate the mature NF-κB2 transcription factor subunit p52. Most of the known pathogenic NFKB2 variants render p100 un-processable and are typically linked to immunodeficiency disorders with antibody deficiency, susceptibility to infections and often … Read more
J Clin Immunol. 2026 Jul 9. doi: 10.1007/s10875-026-02046-6. Online ahead of print. ABSTRACT PURPOSE: 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. … Read more
J Clin Immunol. 2026 Jul 8. doi: 10.1007/s10875-026-02044-8. Online ahead of print. ABSTRACT PURPOSE: 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. METHODS: We conducted … Read more
J Clin Immunol. 2026 Jul 6;46(1):73. doi: 10.1007/s10875-026-02048-4. ABSTRACT 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 … Read more
J Clin Immunol. 2026 Jul 4. doi: 10.1007/s10875-026-02050-w. Online ahead of print. ABSTRACT PURPOSE: 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 … Read more
J Clin Immunol. 2026 Jun 27. doi: 10.1007/s10875-026-02047-5. Online ahead of print. ABSTRACT 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 … Read more
J Clin Immunol. 2026 Jun 25. doi: 10.1007/s10875-026-02030-0. Online ahead of print. ABSTRACT PURPOSE: 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 … Read more
J Clin Immunol. 2026 Jun 19;46(1):67. doi: 10.1007/s10875-026-02040-y. ABSTRACT BACKGROUND: 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. CASE PRESENTATION: We describe a … Read more
J Clin Immunol. 2026 Jun 18. doi: 10.1007/s10875-026-02042-w. Online ahead of print. ABSTRACT PURPOSE: 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. METHODS: The current study investigated this relationship through a retrospective cohort analysis at a … Read more
J Clin Immunol. 2026 Jun 8. doi: 10.1007/s10875-026-02036-8. Online ahead of print. ABSTRACT A novel heterozygous missense variant in STAT3 (NM_139276.3: c.1250G > C, NP_644805.1: p.(Arg417Thr) was identified in a Danish family spanning five generations with diverse phenotypes consistent with autosomal dominant STAT3-Hyper-IgE-Syndrome (STAT3-HIES). Genetic analysis confirmed the absence of the variant in population databases, … Read more
J Clin Immunol. 2026 Jun 9. doi: 10.1007/s10875-026-02038-6. Online ahead of print. ABSTRACT PURPOSE: To perform a systematic review and meta-analysis of prevalence and function of anti-interferon auto-antibodies in acute infectious diseases. METHODS: We performed a search on the following electronic bibliographic databases: Medline, Embase, Web of Science and Cochrane. Eligible studies generated a systematic … Read more
J Clin Immunol. 2026 Jun 5. doi: 10.1007/s10875-026-02035-9. Online ahead of print. ABSTRACT Early diagnosis of inborn errors of immunity (IEIs) can make a difference in patient outcomes and even cut healthcare costs. However, there are some challenges to overcome, such as clinical complexity, low awareness, and limited resources. Generative artificial intelligence has attracted considerable … Read more
J Clin Immunol. 2026 Jun 2. doi: 10.1007/s10875-026-02039-5. Online ahead of print. ABSTRACT Adult-onset immunodeficiency syndrome mediated by anti-interferon-gamma autoantibody (AIGA) is a rare disorder that has garnered increasing recognition in recent years. The condition is most prevalent among adults in Southeast Asia. It is characterized by recurrent disseminated opportunistic infections, frequently involving multiple organ … Read more
J Clin Immunol. 2026 May 22. doi: 10.1007/s10875-026-02034-w. Online ahead of print. ABSTRACT PURPOSE: To report a patient with a novel MSN mutation causing X-linked moesin-associated immunodeficiency (X-MAID) and investigate its pathogenic mechanisms. METHODS: Clinical and immunological data of the patient were collected. Autoantibody levels were measured using antigen microarrays. Whole-exome sequencing was performed to … Read more
J Clin Immunol. 2026 May 20. doi: 10.1007/s10875-026-02033-x. Online ahead of print. ABSTRACT Gain-of-function variants in the TLR7 gene have been associated with a spectrum of clinical manifestations, including systemic lupus erythematosus (SLE)-like disease, neuromyelitis optica, and progressive leukoencephalopathy. The p.(Leu528Ile) variant has previously been shown to underlie this constellation of findings. Here, we report … Read more
J Clin Immunol. 2026 May 19. doi: 10.1007/s10875-026-02026-w. Online ahead of print. ABSTRACT OBJECTIVE: To perform genetic diagnosis and pedigree analysis in a case of autosomal dominant Familial Behçet-like Autoinflammatory Syndrome type 3 (AIFBL3) caused by a novel RELA variant. METHODS: Peripheral blood samples collected from the proband and parents underwent conventional genetic screening, next-generation … Read more
J Clin Immunol. 2026 May 9. doi: 10.1007/s10875-026-02027-9. Online ahead of print. ABSTRACT The Janus Kinase 3 (JAK3) germline gain-of-function (GOF) mutation is a rare inborn error of immunity, first reported in 2020, characterized by lymphopenia and chronic NK-cell proliferation. However, its role in autoimmunity remains unclear, and no direct association with hyper-IgE syndrome (HIES) … Read more
J Clin Immunol. 2026 May 6. doi: 10.1007/s10875-026-02031-z. Online ahead of print. ABSTRACT Dedicator of cytokinesis protein 8 (DOCK8) is a crucial regulator for the formation of immune synapses, allowing for a proper function of innate and adaptive immune systems. DOCK8 deficiency is a primary immunodeficiency, currently known as Inborn Errors of Immunity (IEI) affecting … Read more
J Clin Immunol. 2026 Apr 29. doi: 10.1007/s10875-026-02028-8. Online ahead of print. ABSTRACT Blocking CD154 (CD40L) has the potential to prolong transplanted solid organ graft survival and treat autoimmune diseases. However, first-generation anti-CD154 IgG1 monoclonal antibodies (mAbs) were associated with an increased risk of thrombosis linked to Fc binding to FcγRIIa (CD32A). Here, we describe … Read more
J Clin Immunol. 2026 Apr 21. doi: 10.1007/s10875-026-02025-x. Online ahead of print. ABSTRACT Kawasaki disease (KD) remains the leading cause of acquired heart disease in children. While intravenous immunoglobulin (IVIG) represents standard therapy, approximately 10-20% of patients exhibit treatment refractoriness associated with significantly elevated coronary artery lesion risk. Current risk stratification relies on clinical parameters-fever … Read more
J Clin Immunol. 2026 Mar 28. doi: 10.1007/s10875-026-02008-y. Online ahead of print. ABSTRACT PURPOSE: Congenital athymia is a life-threatening condition characterized by thymic absence and profound T-cell immunodeficiency. Thymus implantation is the definitive treatment, but its availability is limited. This study aimed to evaluate the outcomes of hematopoietic cell transplantation (HCT) as an alternative therapy. … Read more
J Clin Immunol. 2026 Mar 26. doi: 10.1007/s10875-026-02003-3. Online ahead of print. ABSTRACT PURPOSE: Pathogenic variants in the T-cell receptor alpha constant (TRAC) gene have been primarily associated with combined immunodeficiency (CID). To date, only five patients from three unrelated families harboring the same TRAC variant with a CID phenotype, and three patients carrying a … Read more
J Clin Immunol. 2026 Mar 14. doi: 10.1007/s10875-026-01995-2. Online ahead of print. ABSTRACT TREC-NBS identifies patients with inborn errors of immunity (IEI) and syndromic features, but uncertainty remains regarding their immunological management. To address this, syndromic patients detected by TREC-NBS in Germany between August 2019 and April 2024 were systematically analyzed, including phenotype, treatment, and … Read more
J Clin Immunol. 2026 Mar 2. doi: 10.1007/s10875-026-01994-3. Online ahead of print. ABSTRACT AIM: Idiopathic nephrotic syndrome (INS) is the most common glomerular disease in children, but its underlying mechanisms remain unclear. Although glucocorticoids (GC) are the first-line treatment, approximately 10% of INS cases are steroid-resistant (SRNS), and 50% may progress to refractory nephrotic syndrome … Read more
J Clin Immunol. 2026 Feb 11. doi: 10.1007/s10875-026-01984-5. Online ahead of print. ABSTRACT Wiskott-Aldrich syndrome (WAS) is a rare x-linked monogenic immunodeficiency disease, caused by the mutation of WAS gene encoding WAS protein (WASp). Previous findings in WAS patients show B cell perturbations in the periphery, characterized by diminished B-cell numbers and phenotype abnormalities, including … Read more
J Clin Immunol. 2026 Feb 7. doi: 10.1007/s10875-025-01979-8. Online ahead of print. ABSTRACT PURPOSE: Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked (IPEX) syndrome is a rare autoimmune disorder caused by mutations in the FOXP3 gene. Patients with IPEX frequently present with severe dermatitis, diabetes, and enteropathy. This study explores the efficacy of Dupilumab (an anti-IL-4Rα monoclonal antibody) … Read more
J Clin Immunol. 2026 Feb 3. doi: 10.1007/s10875-025-01978-9. Online ahead of print. ABSTRACT PURPOSE: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is successful in pediatric patients with inborn errors of immunity (IEI), but its use in adults is complicated by pre-existing organ damage and increased risk of treatment-related mortality. Ex vivo graft engineering using αβTCR/CD19 depletion … Read more
J Clin Immunol. 2026 Feb 3. doi: 10.1007/s10875-026-01987-2. Online ahead of print. ABSTRACT PURPOSE: 22q11.2 Deletion Syndrome has been primarily described as a disorder of T cell production secondary to thymic hypoplasia. However, there is great complexity in the clinical picture with infections, autoimmunity, and inflammation occurring. Emerging evidence suggests that qualitative T cell dysfunction … Read more
J Clin Immunol. 2026 Jan 27. doi: 10.1007/s10875-025-01968-x. Online ahead of print. ABSTRACT Behçet’s disease (BD) is a chronic inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, skin lesions, and uveitis. Recent genetic studies have identified monogenic diseases with phenotypes resembling BD, including RELA-associated inflammatory disease (RAID), Haploinsufficiency of A20 (HA20), and otulipenia. … Read more
J Clin Immunol. 2026 Jan 10;46(1):4. doi: 10.1007/s10875-025-01967-y. ABSTRACT We describe a 3-year-old patient with xeroderma pigmentosum (XP) and genetically confirmed XPA deficiency who presented with recurrent infections in early childhood. Immunological assessment revealed mild hypogammaglobulinemia with IgG2 and IgG3 subclass deficiencies, as well as impaired humoral immunity demonstrated by a reduced antibody response to … Read more
J Clin Immunol. 2026 Jan 6. doi: 10.1007/s10875-025-01972-1. Online ahead of print. ABSTRACT Patient-reported outcomes are critical to multidisciplinary, patient-centred approaches in diseases requiring lifelong management. Among inborn errors of immunity (IEIs), reports on this subject are typically limited to specific diagnostic subgroups or focus narrowly on the route of immunoglobulin replacement therapy (IgRT), offering … Read more
J Clin Immunol. 2026 Jan 2. doi: 10.1007/s10875-025-01973-0. Online ahead of print. ABSTRACT The tumor necrosis factor (TNF) receptor superfamily member, transmembrane activator and CAML interactor (TACI) encoded by TNFRSF13B, are extensively involved in immune responses. In our previous work, TNFRSF13B exon 2 variants were recurrently identified in chronic active Epstein-Barr virus disease (CAEBV). Here … Read more
J Clin Immunol. 2025 Dec 27. doi: 10.1007/s10875-025-01974-z. Online ahead of print. ABSTRACT OBJECTIVE: The presence of unique monocyte subsets and sub-populations plays a significant role in the onset and progression of rheumatic diseases. This study aimed to characterize variations in monocyte subsets and sub-populations and functional roles in patients with primary Sjögren’s syndrome (pSS) … Read more
J Clin Immunol. 2025 Dec 26. doi: 10.1007/s10875-025-01955-2. Online ahead of print. ABSTRACT Type II interferon (IFN) immunity is crucial for controlling intramacrophagic infections, driven by the interaction between innate immunity (macrophage-derived IL-12) and adaptive immunity (Th-derived IFN-γ). This study examines the maturation of type II IFN immunity in 55 healthy children (ages 1-18) to … Read more
J Clin Immunol. 2025 Dec 24. doi: 10.1007/s10875-025-01977-w. Online ahead of print. ABSTRACT Trained immunity, a de-facto innate immune memory, has been extensively studied in response to live-attenuated vaccines, but its presence following the new COVID-19 vaccines has not yet been fully elucidated. In this study, we investigate markers of trained immunity in individuals vaccinated … Read more
J Clin Immunol. 2025 Dec 12. doi: 10.1007/s10875-025-01970-3. Online ahead of print. ABSTRACT INTRODUCTION: Primary ‘predominantly antibody deficiencies’ (PADs) are rare disorders characterized by increased susceptibility to infections, autoimmunity, allergies, and malignancies. Their low prevalence and heterogeneity often delay diagnosis, increasing morbidity and mortality. This study identifies infection patterns in PAD patients and analyzes predictors … Read more
J Clin Immunol. 2025 Dec 10. doi: 10.1007/s10875-025-01969-w. Online ahead of print. ABSTRACT PURPOSE: Long COVID (LC) is a long-term debilitating disease of which the exact pathophysiology is unknown. A dysregulated immune response resulting in hyperresponsive immune cells is hypothesized as a key mechanism in the development of LC. Several studies suggest that acute infections … Read more
J Clin Immunol. 2025 Nov 28. doi: 10.1007/s10875-025-01966-z. Online ahead of print. ABSTRACT PURPOSE: Despite well-conducted replacement therapy with polyvalent immunoglobulins (IgRT), some patients with primary immunodeficiencies (PID) continue to experience recurrent or chronic infections. IgA and IgM, essential for mucosal and complement-mediated immunity, are absent or minimal in standard immunoglobulin products. The aim of … Read more
J Clin Immunol. 2025 Nov 28. doi: 10.1007/s10875-025-01965-0. Online ahead of print. ABSTRACT Exosomes, as integral mediators of cellular communication, have emerged as crucial players in the pathogenesis and potential treatment of autoimmune diseases. This review explores the dual role of exosomes in mediating autoantigen presentation and their impact on immune dysregulation. Exosomes, by virtue … Read more
J Clin Immunol. 2025 Nov 27. doi: 10.1007/s10875-025-01919-6. Online ahead of print. ABSTRACT Autosomal recessive mutations in TAP1, TAP2, TAPBP, or B2M, are associated with major histocompatibility complex (MHC) class I deficiency. Individuals may present with granulomatous skin ulceration, but the underlying antigenic triggers remain largely unknown. We identified TAP1 deficiency in a 32-year-old female … Read more
J Clin Immunol. 2025 Nov 25;45(1):168. doi: 10.1007/s10875-025-01963-2. ABSTRACT BACKGROUND: Common Variable Immunodeficiency (CVID) is a group of heterogeneous disorders with common denominators of impaired antibody production and function, and recurrent infections. Currently, prognostic biomarkers for CVID are limited. CXCL13 is a critical regulator of germinal centre responses and antibody production, with T follicular helper … Read more
J Clin Immunol. 2025 Nov 25;45(1):167. doi: 10.1007/s10875-025-01957-0. ABSTRACT Down syndrome (DS) and STAT1 gain-of-function (GOF) share clinical and molecular features, including persistent inflammation. We aimed to investigate whether the coexistence of DS and a STAT1 GOF mutation in a patient synergistically enhances interferon (IFN) signaling and exacerbates inflammatory responses, posing additional management challenges. Two … Read more
J Clin Immunol. 2025 Nov 25;45(1):166. doi: 10.1007/s10875-025-01945-4. ABSTRACT BACKGROUND: Newborn screening (NBS) by quantification of T-cell receptor excision circles (TREC) identifies a considerable number of infants with T-cell lymphopenia (TCL) other than severe combined immunodeficiency (SCID). While some of these children have well-defined inborn errors of immunity (IEI), many lack a clear genetic diagnosis, … Read more
J Clin Immunol. 2025 Nov 26. doi: 10.1007/s10875-025-01961-4. Online ahead of print. ABSTRACT BACKGROUND AND OBJECTIVES: Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease primarily affecting the axial skeleton. Despite significant advances, its pathogenic mechanisms remain unclear, posing challenges to early diagnosis and effective treatment. This study aims to elucidate the pathogenic pathways of … Read more
J Clin Immunol. 2025 Nov 23. doi: 10.1007/s10875-025-01947-2. Online ahead of print. ABSTRACT INTRODUCTION: Inborn errors of immunity (IEIs) constitute a diverse group of more than 500 disorders resulting from pathogenic variants in over 500 causative genes, with most being monogenic diseases. The use of exome sequencing based on next-generation sequencing technologies has significantly advanced … Read more
J Clin Immunol. 2025 Nov 18;45(1):163. doi: 10.1007/s10875-025-01964-1. ABSTRACT PURPOSE: This study aimed to investigate the spectrum of bacterial infections in children with inborn error of immunity (IEIs). METHODS: Pediatric patients with IEIs and positive for bacteria considered to be pathogenic were included in this retrospective study. RESULTS: In this study, 1811 medical records of … Read more
J Clin Immunol. 2025 Nov 18;45(1):162. doi: 10.1007/s10875-025-01959-y. ABSTRACT Flow cytometric immunophenotyping of lymphocytes and dendritic cells, and functional lymphocyte mitogen response tests are used in the diagnostics of inborn errors of immunity (IEI), especially in pediatrics. These routinely used tests lack sufficient age-matched reference values in children. We established reference values for lymphocyte and … Read more
J Clin Immunol. 2025 Nov 18;45(1):165. doi: 10.1007/s10875-025-01958-z. ABSTRACT Suppressor of cytokine signaling 1 (SOCS1) haploinsufficiency is a recently described inborn error of immunity characterized by autoimmunity, inflammation, lymphoproliferation, and increased infection susceptibility. SOCS1, a negative regulator of cytokine signaling via the JAK/STAT pathway, explains the condition’s broad phenotypic variability. Single nucleotide polymorphisms in SOCS1 … Read more
J Clin Immunol. 2025 Nov 15;45(1):160. doi: 10.1007/s10875-025-01953-4. ABSTRACT BACKGROUND: Treating neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remains a challenge. Managing excessive infiltration and activation of neutrophils in tissues is important for improving CRSwNP outcomes. S100A4, a calcium-binding protein, regulates cell migration, chemotaxis and tissue fibrosis. In this study, we sought to … Read more
J Clin Immunol. 2025 Nov 15;45(1):161. doi: 10.1007/s10875-025-01962-3. ABSTRACT X-linked agammaglobulinemia (XLA) is caused by loss-of-function variants in Bruton’s tyrosine kinase, leading to absence of circulating B lymphocytes and inability to produce antibodies. Despite the fear that patients with XLA would be at high risk for severe infection when the novel virus SARS-CoV-2 emerged in … Read more
J Clin Immunol. 2025 Nov 12;45(1):159. doi: 10.1007/s10875-025-01960-5. ABSTRACT Haploinsufficiency of cytotoxic T-lymphocyte associated protein 4 (CTLA4), a known cause of inborn errors of immunity, can lead to autoimmunity, inflammation, neoplasia and infections. A previously undescribed CTLA4 variant was identified in a patient who presented with life-threatening cutaneous infection caused by Pseudomonas aeruginosa, severe VZV … Read more
