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
J Clin Immunol. 2025 Nov 12;45(1):158. doi: 10.1007/s10875-025-01952-5. ABSTRACT Intravenous immunoglobulin (IVIG) therapy is a well-documented and effective treatment for primary immunodeficiencies (PI). Subcutaneous immunoglobulins (SCIG) have emerged as an effective alternative for some patients that offers additional flexibility.Currently, caprylate/chromatography purified IGSC (human) 20% is approved to treat PI in North America and many countries … Read more
J Clin Immunol. 2025 Nov 10;45(1):157. doi: 10.1007/s10875-025-01946-3. ABSTRACT BACKGROUND: IgA vasculitis (IgAV) is an autoimmune disorder characterized by inflammation of the small blood vessels. The pathogenesis of IgAV is believed to involve a complex interplay between immune cells, metabolites, and inflammatory cytokines (ICs). METHODS: We performed two-sample Mendelian randomization (MR) analysis to examine the … Read more
J Clin Immunol. 2025 Nov 10;45(1):156. doi: 10.1007/s10875-025-01956-1. ABSTRACT Combined immunodeficiency due to CARMIL2 mutations is a rare autosomal recessive primary immunodeficiency characterized by impaired T-cell activation and function, leading to diverse clinical manifestations. Fewer than 50 cases have been reported worldwide. We describe the clinical and genetic features of five patients from Palestine with … Read more
J Clin Immunol. 2025 Nov 7;45(1):153. doi: 10.1007/s10875-025-01940-9. ABSTRACT Fungal infections contribute to a significant disease burden in patients with chronic granulomatous disease (CGD). While the presentation may differ depending on genotype and environmental exposure to fungus, associated mortality rates are universally high. This is a retrospective study wherein medical records of patients diagnosed with … Read more
J Clin Immunol. 2025 Nov 8;45(1):154. doi: 10.1007/s10875-025-01927-6. ABSTRACT PURPOSE: Patients with X-linked agammaglobulinemia (XLA) suffer from severe, recurrent infections potentially leading to life-threatening complications. Early diagnosis and timely treatment can prevent infections and secondary complications, emphasizing a role for newborn screening (NBS). NBS for XLA is based on quantification of kappa-deleting recombination excision circles … Read more
J Clin Immunol. 2025 Nov 6;45(1):152. doi: 10.1007/s10875-025-01903-0. ABSTRACT BACKGROUND: Non-Aspergillus invasive fungal infections (NAFI) are increasingly reported in patients with Chronic Granulomatous Disease (CGD), but precise clinical descriptions remain scarce. OBJECTIVE AND METHODS: We conducted a retrospective analysis of NAFI cases among CGD patients in the French National Registry of Primary Immunodeficiencies (CEREDIH) and … Read more
J Clin Immunol. 2025 Nov 5;45(1):150. doi: 10.1007/s10875-025-01951-6. ABSTRACT PURPOSE: Bone marrow failure (BMF) in idiopathic aplastic anemia (AA) and hypoplastic myelodysplastic neoplasms (MDS-h) results from the destruction of hematopoietic progenitors by autoreactive T cells; however, the molecular events driving the pathogenesis of these disorders remain unclear. We therefore applied whole-exome sequencing (WES) in AA … Read more
J Clin Immunol. 2025 Oct 21;45(1):148. doi: 10.1007/s10875-025-01934-7. ABSTRACT BACKGROUND: Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked(IPEX) syndrome caused by FOXP3 mutations is rare. FOXP3 is a transcription factor required for the regulatory T cell (Treg) development/function. AIM: We aimed to characterize the clinical, immunologic, and genetic features of a single-center cohort of IPEX syndrome. PATIENTS … Read more
J Clin Immunol. 2025 Oct 21;45(1):149. doi: 10.1007/s10875-025-01943-6. ABSTRACT The cellular basis of COVID-19 severity in patients with deficiencies in type I IFN immunity remains unclear. In this study, we differentiated cardiomyocytes and macrophages from IFNAR1 competent (IFNAR1comp) and deficient (IFNAR1def) induced pluripotent stem cells (iPSCs), and analyzed virus replication and cytokine production after exposure … Read more
J Clin Immunol. 2025 Oct 20;45(1):147. doi: 10.1007/s10875-025-01950-7. ABSTRACT BACKGROUND: Inborn errors of immunity (IEI) affecting B-cell receptor signaling cause predominantly antibody deficiency (PAD) with varying degrees of severity. Recently, four heterozygous variants in SYK were reported to cause hypogammaglobulinemia, multiorgan inflammatory disease and diffuse large B-cell lymphoma. OBJECTIVE: We aimed to unravel the genetic … Read more
J Clin Immunol. 2025 Oct 16;45(1):143. doi: 10.1007/s10875-025-01949-0. ABSTRACT Hypogammaglobulinemia (HG) predisposes patients to gastrointestinal Campylobacter infections. This prospective study determined the prevalence of Campylobacter in stool samples from patients with immunoglobulin (Ig)-substituted HG at Bordeaux University Hospital. 73 patients (42 women, median age: 61) receiving Ig substitution therapy were enrolled from July 2022 to … Read more
J Clin Immunol. 2025 Oct 16;45(1):144. doi: 10.1007/s10875-025-01936-5. ABSTRACT BACKGROUND: Primary immunodeficiency disease (PID)/Inborn Errors of Immunity (IEI) with T-cell dysfunction is well-known for susceptibility to opportunistic/viral infections. Epstein-Barr virus-positive smooth muscle tumor (EBV-SMT) is a rare entity primarily seen in the setting of immunodeficiency, such as transplantation, HIV/AIDS, and IEI. AIM: This study aimed … Read more
J Clin Immunol. 2025 Oct 1;45(1):141. doi: 10.1007/s10875-025-01929-4. ABSTRACT INTRODUCTION: Specific determinants of target-organ damage in autoimmune diseases are complex and multifactorial, several genetic and environmental factors are recognized but mostly remain unknown. Immunotherapy with “check-point inhibitors” (CPI) is complicated by immune related adverse events (IRAE), occurring in a large fraction of patients, with organ-specific … Read more
J Clin Immunol. 2025 Sep 30;45(1):137. doi: 10.1007/s10875-025-01937-4. ABSTRACT OBJECTIVE: Germline heterozygous gain-of-function (GOF) mutations in STAT1 impair IL-17-mediated immunity, resulting in carriers’ susceptibility to chronic mucocutaneous candidiasis (CMC). JAK inhibitors have shown therapeutic effectiveness in patients with STAT1-GOF mutations. METHODS: The mutation was detected using whole-exome sequencing (WES) and confirmed by Sanger sequencing. The … Read more
J Clin Immunol. 2025 Sep 30;45(1):131. doi: 10.1007/s10875-025-01926-7. ABSTRACT BACKGROUND: The CYBB gene encodes the gp91-phox protein, a critical component of the NADPH oxidase complex involved in pathogen clearance. Mutations in CYBB are associated with chronic granulomatous disease (CGD), leading to recurrent bacterial infections. OBJECTIVE: To understand the genetic causes of Chinese CGD patients. METHODS: … Read more
J Clin Immunol. 2025 Sep 30;45(1):138. doi: 10.1007/s10875-025-01932-9. ABSTRACT VEXAS syndrome is an adult-onset autoinflammatory disorder caused by somatic UBA1 variants, but there are no standardized criteria for genetic testing or diagnostics. This study compared Sanger sequencing and next-generation sequencing (NGS) for detecting UBA1 variants in patients with suspected VEXAS, assessed the ability of Sanger … Read more
J Clin Immunol. 2025 Sep 30;45(1):129. doi: 10.1007/s10875-025-01920-z. ABSTRACT PURPOSE: Enteropathy is a non-infectious complication in Common Variable Immune Deficiency (CVID) associated with increased morbidity and mortality. We characterized this group of CVID enteropathy (CVID-E) patients and investigated the effectiveness of immunosuppressive treatments on its clinical course. METHOD: We identified patients with CVID-E in two … Read more
