Journal of Clinical Immunology最新文献

{"title":"Type I IFNs Decrease SARS-CoV-2 Replication in Human Cardiomyocytes and Increase Cytokine Production in Macrophages.","authors":"Verónica Durán, Eirini Nikolouli, Shambhabi Chatterjee, Bibiana Costa, Andreas Pavlou, Annett Ziegler, Jennifer Becker, Kira Baumann, Matthias Bruhn, Kathrin Haake, Anna Rafiei Hashtchin, Ingrid Gensch, Andrea Korte, Yvonne Lisa Behrens, Shen-Ying Zhang, Jean-Laurent Casanova, Christian Bär, Nico Lachmann, Thomas Thum, Ulrich Kalinke","doi":"10.1007/s10875-025-01943-6","DOIUrl":"10.1007/s10875-025-01943-6","url":null,"abstract":"<p><p>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 (IFNAR1^comp) and deficient (IFNAR1^def) induced pluripotent stem cells (iPSCs), and analyzed virus replication and cytokine production after exposure to SARS-CoV-2. Cardiomyocytes expressed the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and showed abundant SARS-CoV-2 replication, which was higher in IFNAR1^def than IFNAR1^comp cells. Treatment with exogenous IFNα mitigated infection in IFNAR1^comp, but not in IFNAR1^def cardiomyocytes. In contrast, macrophages did not express ACE2 and did not support SARS-CoV-2 replication, but produced pro-inflammatory cytokines upon virus exposure, which was impaired in IFNAR1^def macrophages. In conclusion, type I IFNs decrease SARS-CoV-2 replication in human iPSC-derived cardiomyocytes, while they increase cytokine responses of macrophages.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"149"},"PeriodicalIF":5.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337090","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":"Beyond the Classical Triad: Atypical Presentations and Regulatory T Cell Phenotyping in a Cohort of IPEX Patients.","authors":"Ismail Yaz, Sevil Oskay Halacli, Canberk Ipsir, Baris Ulum, Elif Soyak Aytekin, Hacer Neslihan Bildik, Melike Ocak, Hanife Avci, Fatma Visal Okur, Hayriye Hizarcioglu Gulsen, Hulya Demir, Ayse Metin, Alev Ozon, Baris Kuskonmaz, Ilhan Tezcan, Saliha Esenboga, Deniz Cagdas","doi":"10.1007/s10875-025-01934-7","DOIUrl":"10.1007/s10875-025-01934-7","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>We aimed to characterize the clinical, immunologic, and genetic features of a single-center cohort of IPEX syndrome.</p><p><strong>Patients and methods: </strong>We present the clinical/immunological/genetic features of 12 patients with IPEX syndrome. We used whole exome and Sanger sequencing for the diagnosis/familial segregation. We performed immunophenotyping and measured Treg percentage and FOXP3 expression in peripheral blood by flow cytometric analysis.</p><p><strong>Results: </strong>Median age at diagnosis was 2.5 years (range: 0.3-22 years). Common clinical manifestations were infections (n = 9, 75%), allergies (n = 8, 67%), autoimmunity (n = 7, 58%), enteropathy (n = 7, 58%), and lymphoproliferation (n = 3, 25%). Atypical initial presentations included class IV lupus nephritis, a SCID-like immunophenotype (CD3⁺ T cells: 4% [100/µL]; CD4⁺ T cells: 3%, CD8⁺ T cells: 1%, CD19⁺ B cells: 81%, CD16/56⁺ NK cells: 13%), and isolated hypogammaglobulinemia persisting for years during follow-up. At the time of diagnosis, three (25%) patients had leukopenia, six (50%) had lymphopenia and two (17%) had neutropenia. Eosinophilia was observed in 42% of patients (25% mild, 17% moderate). Six different variants in FOXP3 were characterized in 12 patients from nine unrelated families. Four (33%) patients underwent hematopoietic stem cell transplantation (HSCT). Overall, three (25%) patients died due to infections. One patient died due to HSCT-related catheter complications, one patient died in an accident. Among the transplanted patients, two are alive and well. Among the non-transplanted patients, five are alive and are being followed up at our center. Treg (CD4⁺CD127^-/lowCD25⁺Foxp3⁺) percentage was low in eight patients compared to healthy controls (p < 0.001). FOXP3 expression was low in all the patients compared to healthy controls.</p><p><strong>Conclusion: </strong>Atypical presentations make the diagnosis of IPEX syndrome challenging. This study expands the current knowledge of IPEX syndrome by describing a single-center cohort with certain atypical manifestations and by confirming previously reported rare phenotypes. Elucidating the genetic basis of immunodeficiency diseases contributes to improving diagnostic approaches and patient management.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"148"},"PeriodicalIF":5.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337040","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":"Novel SYK Variant Causes Enhanced SYK Autophosphorylation and PI3K Activation in an Antibody-Deficient Patient.","authors":"Emily S J Edwards, Josh Chatelier, Gregory I Snell, Go Hun Seo, Rin Khang, Robyn E O'Hehir, Julian J Bosco, Menno C van Zelm","doi":"10.1007/s10875-025-01950-7","DOIUrl":"10.1007/s10875-025-01950-7","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We aimed to unravel the genetic and functional cause of PAD in a 43-year-old female presenting with hypogammaglobulinemia, congenital heart disease and pulmonary hypertension requiring lung transplantation.</p><p><strong>Methods: </strong>Patient gDNA was subjected to whole-exome and Sanger sequencing. Blood B- and T-cell subsets, as well as tonic and antigen-receptor induced expression levels of phosphorylated-SYK, phosphorylated-ribosomal S6 and phosphorylated p38 were evaluated by flow cytometry.</p><p><strong>Results: </strong>A novel heterozygous missense SYK variant was identified, mutating a residue in the protein kinase domain (c.1769G > A; p.R590Q), which is highly conserved across vertebrates. While total B- and T-cell numbers were within the normal range, the patient had reduced unswitched and class-switched memory B-cell numbers. Resting B cells from the patient demonstrated enhanced autophosphorylation of SYK, and tonic and ligand-induced phospho-S6 levels. Spontaneous SYK autophosphorylation, S6 and p38 phosphorylation were recapitulated in a pre-clinical cell model, i.e. expression of the SYK R590Q variant in HEK293T cells.</p><p><strong>Conclusions: </strong>We identified a novel gain-of-function variant in SYK to underlie hypogammaglobulinemia and atypical autoinflammatory disease. Flowcytometric screening for phospho-S6 in lymphocytes of IEI patients can guide genetic diagnosis of B-cell signaling abnormalities.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"147"},"PeriodicalIF":5.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329450","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":"A Novel Hypomorphic STAT3 Gene Variant in a 7-year-old Male with Hyper-IgE Syndrome.","authors":"Tomoko Higashigawa, Yukiko Ikeyama, Kosuke Ashihara, Takaki Asano, Satoshi Okada, Yuki Miwa, Katsumi Sugiura, Hidenori Ohnishi","doi":"10.1007/s10875-025-01942-7","DOIUrl":"10.1007/s10875-025-01942-7","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"146"},"PeriodicalIF":5.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329437","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 Histoplasmosis in Very Early Diagnosed De Novo STAT3-HIES.","authors":"Armen Sanosyan, Ran Hazan, Alexandra F Freeman, Erica G Schmitt, Caroline C Horner","doi":"10.1007/s10875-025-01923-w","DOIUrl":"10.1007/s10875-025-01923-w","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"145"},"PeriodicalIF":5.7,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308207","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":"Epstein-Barr Virus-Associated Smooth Muscle Tumors in inborn Errors of Immunity: A single-center Case Series and Literature Overview.","authors":"Gulnar Aliyeva, Inci Yaman Bajin, Diclehan Orhan, Tezer Kutluk, Kemal Kösemehmetoğlu, Deniz Cagdas","doi":"10.1007/s10875-025-01936-5","DOIUrl":"10.1007/s10875-025-01936-5","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>This study aimed to characterize patients' clinical/immunologic/genetic features with EBV-SMT and assess their association with IEI.</p><p><strong>Methods: </strong>We reviewed the medical records of patients with EBV-SMT in an outpatient immunology clinic and analyzed a total of 33 patients, including 24 identified from the literature.</p><p><strong>Results: </strong>The study included nine patients (male/ female = 6/3). The median ages at the onset of symptoms, clinical diagnosis of PID, genetic diagnosis, and EBV-SMT diagnosis were 12 months (1-84 months), 6 years (2-15 years), 10 years (6-18 years), and 10 years (4-18 years), respectively. The parental consanguinity ratio was 7/9(78%). Four patients had combined immunodeficiency. Five out of nine patients (56%) received a genetic IEI diagnosis: JAK3 deficiency (n = 1), STAT1 GOF (n = 1), CARMIL2 deficiency (n = 1), DOCK8 deficiency (n = 1), and ITK deficiency (n = 1). Recurrent infections (100%), chronic diarrhea/colitis (78%), organomegaly (67%), and lymphadenopathy (56%) were prevalent among the patients. Six patients exhibited leiomyoma-like morphology, while three had leiomyosarcoma-like morphology. Five out of nine patients (55%) died, two of whom succumbed due to the complications of hematopoietic stem cell transplantation.</p><p><strong>Conclusion: </strong>EBV-SMT may suggest an underlying immunodeficiency. Since the mortality is high, early genetic diagnosis of IEI, monitoring the patients with IEI for chronic EBV and cancer, and an individualized therapeutic approach will minimize complications.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"144"},"PeriodicalIF":5.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12532746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300732","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":"Stool Screening for Campylobacter Species in Hypogammaglobulinemic Patients Receiving Immunoglobulin Therapy.","authors":"Basile Mechernene, Philippe Lehours, Etienne Rivière, Noémie Gensous, Claire Tinévez, Pierre Duffau, Félix Blaison, Camille Prot-Leurent, Thomas Pires, Carine Greib, Thibaut Zannese, Martine Dubois, Lucie Bénéjat, Astrid Ducournau, Johanna Aptel, Quentin Jehanne, Jean-François Viallard, Estibaliz Lazaro","doi":"10.1007/s10875-025-01949-0","DOIUrl":"10.1007/s10875-025-01949-0","url":null,"abstract":"<p><p>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 July 2024. Stool samples were analysed with culture, PCR, faecal calprotectin levels, and immune profiles were also assessed. A second stool sample was collected from 38 patients after 6-12 months, totalling 111 samples. 53 patients had primary HG (32 common variable immunodeficiency, 7 IgG subclass deficiencies, 4 Bruton's agammaglobulinemias) and 20 had secondary HG (7 drug-induced, 8 lymphoid hemopathy-related, 5 mixed). Campylobacter were detected in 11 patients (15.1%), with species identified as Campylobacter jejuni, Campylobacter coli, and Aliarcobacter butzleri. Diarrhea was reported in 42% of Campylobacter-positive patients versus 15% of negative patients. Campylobacter-positive patients exhibited higher median faecal calprotectin levels (255 µg/g vs. 52 µg/g). Among positive patients, 44% (versus 34% in negative patients) had non-infectious complications such as immune complications. Mean residual IgG levels were similar between groups, although IgA and IgM were lower in Campylobacter-positive patients (0 vs. 0.36 g/L and 0.17 vs. 0.40 g/L, respectively). The mean CD4/CD8 ratio was also lower in the positive group (1.71 ± 0.85 vs. 2.06 ± 1.18). This study reveals a high prevalence of Campylobacter in HG patients despite receiving Ig therapy. Elevated faecal levels of calprotectin in symptomatic patients suggests active infection. Screening for Campylobacter should be considered in HG patients presenting with digestive symptoms.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"143"},"PeriodicalIF":5.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12532628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300742","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: Self-reported Clinical Outcomes and Quality of Life in Agammaglobulinemia: the Importance of an Early Diagnosis.","authors":"Maartje Blom, Annelotte J Duintjer, Mahnaz Jamee, Melanie de Gier, Markéta Bloomfield, Adam Klocperk, Pavlina Kralickova, Neslihan E Karaca, Oksana Boyarchuk, Peter Čižnár, Miloš Jeseňák, Svetlana Sharapova, Ekaterina Skopovets, Luis I Gonzalez-Granado, Serena Palmeri, Stefano Volpi, Andrea Martin Nalda, Sonia Rodriguez Tello, Pere Soler-Palacín, Hassan Abolhassani, Federica Pulvirenti, Bianca Cinicola, Uwe Wintergerst, Godelieve J de Bree, J Merlijn van den Berg, Helen L Leavis, Clementien Vermont, Virgil A S H Dalm, Koen van Aerde, Stefanie Henriet, Hetty Jolink, Judith Potjewijd, Arjan Lankester, Chandoshi Rhea Mukherjee, Dagmar Berghuis, Małgorzata Pac, Benjamin M J Shillitoe, Andrew R Gennery, Mirjam van der Burg","doi":"10.1007/s10875-025-01944-5","DOIUrl":"10.1007/s10875-025-01944-5","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"142"},"PeriodicalIF":5.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251507","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":"The Targets of Immune Adverse Events in Cancer Immunotherapy by Combined Check-point Inhibitors Resemble those Seen in IPEX Patients.","authors":"Maria Francisca Moraes-Fontes, Jocelyne Demengeot, António Coutinho","doi":"10.1007/s10875-025-01929-4","DOIUrl":"10.1007/s10875-025-01929-4","url":null,"abstract":"<p><strong>Introduction: </strong>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 inflammation of immunologic aetiology. We hypothesized that such IRAE are associated to regulatory T cell (Treg) dysfunction. To start testing this hypothesis, we have now compared organ targets of CPI-induced IRAE with those described in IPEX (Immune dysregulation polyendocrinopathy enteropathy X-linked) patients carriers of deleterious mutations in the Foxp3 gene leading to deficient/absent Treg.  METHOD: We compared the frequency of autoimmune diseases (AID) in three groups of conditions: CPI-induced IRAE, IPEX patients, and the General Population (GP) through a PubMed search from 01/01/1998 to 31/05/2024. For each group, and each autoimmune disease, the highest reported frequency was selected, listed in reference to CPI-IRAE and classified from the highest to lowest prevalence. Identified were enteropathy, rash (eczema or other dermatitis), transaminitis/hepatitis, hypothyroidism, increased lipase/exocrine pancreatitis, arthralgia/inflammatory arthritis, hypophysitis, adrenal insufficiency, type 1 diabetes mellitus, haemolytic anaemia, Sjögren´s syndrome, polymyalgia rheumatica, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis and systemic sclerosis.  RESULTS: While dermatitis and thyroid disease are also the most frequent AID in the GP, the latter, together with enteropathy, hepatitis, and adrenal insufficiency are much more frequent in CPI-IRAE and IPEX. Of note, the most frequent systemic AID in the GP such as de novo Sjögren´s syndrome, polymyalgia rheumatica, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis and systemic sclerosis are extremely rare in CPI-IRAE (few case reports) and not described in IPEX.</p><p><strong>Conclusion: </strong>Our finding provides further evidence for the possibility that the functional inhibition/inactivation of Treg is a plausible contributing mechanism in the physiopathology of CPI-IRAE.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"141"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199444","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":"Novel Compound Heterozygous Mutations in HOIP Result in Autoinflammation and Immunodeficiency.","authors":"Li Wang, Jing Xiao, Rui Gan, Xuemei Tang, Junfeng Wu","doi":"10.1007/s10875-025-01939-2","DOIUrl":"10.1007/s10875-025-01939-2","url":null,"abstract":"<p><strong>Objective: </strong>Mutations in the HOIP gene, encoding Heme-oxidized IRP2 ubiquitin ligase-1 (HOIL-1) interacting protein, a key component of the linear ubiquitination chain assembly complex (LUBAC), affect the activation of the NF-κB pathway and result in autoinflammation and immunodeficiency. To date, only three patients with HOIP mutations have been reported in the English literature. This study aimed to identify the genetic cause in a 1-year-6-month-old boy with early-onset autoinflammation and immunodeficiency.</p><p><strong>Methods: </strong>Clinical manifestations and immunological phenotypes were assessed in a Chinese patient with novel compound heterozygous mutations in HOIP. Swiss-PdbViewer was used to predict the pathogenicity of the mutations. HOIP and LUBAC protein levels were evaluated by western blot. Immunological phenotypes and intracellular NF-κB phosphorylation in T and B cells were analyzed by flow cytometry, and the interferon (IFN) signature was assessed using quantitative reverse transcription PCR (RT-qPCR).</p><p><strong>Results: </strong>The patient experienced recurrent fever, multiple site infections, and chronic diarrhea from the neonatal period, requiring repeated hospitalizations. Targeted gene sequencing identified novel compound heterozygous mutations in HOIP (c.1654 C > T, p.Gln552Ter; c.3038 A > C, p.His1013Pro). These mutations significantly reduced HOIP and LUBAC protein expression and altered the HOIP protein structure. Immunophenotyping revealed a reduction in CD8 + T cells, central memory (CD8 CM) and effector memory (CD8 EM) T cells, and CD4 + T cells. Subset analysis of CD4 + T cells showed decreased T follicular helper cells (Tfh) and increased IL-17-producing T helper (Th17) cells. The patient also exhibited a higher percentage of naïve B cells and a lower percentage of memory B cells, alongside impaired NF-κB phosphorylation in T and B cells upon LPS stimulation. The expression of the patient's interferon-stimulated gene (ISG) was markedly higher than that of healthy controls.</p><p><strong>Conclusion: </strong>HOIP mutations may lead to multiple immune abnormalities, impaired NF-κB activation, and activation of the type I interferon pathway. These findings highlight the diversity of HOIP mutations and expand the clinical spectrum of associated diseases.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"135"},"PeriodicalIF":5.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199706","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}