Journal of Clinical Immunology最新文献

{"title":"2025: Onward and Upward!","authors":"Vincent R Bonagura","doi":"10.1007/s10875-025-01879-x","DOIUrl":"https://doi.org/10.1007/s10875-025-01879-x","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"91"},"PeriodicalIF":7.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007747","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":"Quality of Life in Japanese Patients with Primary Immunodeficiency Disease is Disrupted throughout the Year.","authors":"Toshinao Kawai, Hirokazu Kanegane, Masataka Ishimura, Satoshi Okada, Nobuaki Okamatsu, Kaori Nakagawa, Madoka Go, Shinichi Noto","doi":"10.1007/s10875-025-01869-z","DOIUrl":"https://doi.org/10.1007/s10875-025-01869-z","url":null,"abstract":"<p><p>Patients with primary immunodeficiency disease (PID) have an increased susceptibility to infection and may experience negative impacts on health-related quality of life (HR-QOL) and activities of daily living. This prospective observational study of patients aged ≥ 12 years with PID assessed HR-QOL, work impairment, and disease-related daily burden over a full year, with a focus on seasonal variation. The study period was from October 2021 to November 2023. Data were collected using an online system. HR-QOL was assessed using EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), work impairment with the Work Productivity and Activity Impairment (WPAI) questionnaire, and disease-related burden with a questionnaire designed for this study. In patients with PID (N = 56) and healthy volunteers (N = 43), no significant seasonal variation was observed in EQ-5D-5L, SF-36, or WPAI scores. With few exceptions, patients with PID had significantly lower EQ-5D-5L, SF-36, and WPAI scores than healthy volunteers in all seasons. In patients with PID, disease-related symptoms and limitations of daily living persisted throughout the year, regardless of season. In conclusion, patients with PID had lower quality of life and were more socially, physically, and mentally stressed in all seasons compared with healthy individuals.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"90"},"PeriodicalIF":7.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017101","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 Germline Heterozygous Dominant Negative IKZF2 Variant Causing Syndromic Primary Immune Regulatory Disorder and ICHAD.","authors":"Henry Y Lu, Maryam Vaseghi-Shanjani, Avery J Lam, Mehul Sharma, Arezoo Mohajeri, Leandro B R Silva, Jana Gillies, Gui Xiang Yang, Susan Lin, Maggie P Fu, Areesha Salman, Ronak Rahmanian, Linlea Armstrong, Jessica Halparin, Connie L Yang, Mark Chilvers, Erika Henkelman, Wingfield Rehmus, Douglas Morrison, Audi Setiadi, Sara Mostafavi, Michael S Kobor, Frederick K Kozak, Catherine M Biggs, Clara van Karnebeek, Kyla J Hildebrand, Megan K Levings, Stuart E Turvey","doi":"10.1007/s10875-025-01882-2","DOIUrl":"https://doi.org/10.1007/s10875-025-01882-2","url":null,"abstract":"<p><p>Monogenic defects that impair the control of inflammation and tolerance lead to profound immune dysregulation, including autoimmunity and atopy. Studying these disorders reveals important molecular and cellular factors that regulate human immune homeostasis and identifies potential precision medicine targets. Here, we provide a detailed immunological assessment of a pediatric patient with a recently discovered syndrome causing Immunodysregulation, Craniofacial anomalies, Hearing impairment, Athelia, and Developmental delay (or ICHAD syndrome). The immunodysregulation resulted in autoimmune hemolytic anemia (AIHA) and atopic dermatitis. The patient carried a de novo germline heterozygous c.406+540_574+13477dup;p.Gly136_Ser191dup variant in IKAROS family zinc finger 2 (IKZF2), which encodes HELIOS. This variant led to reduced HELIOS protein expression and dominant interference of wild-type HELIOS-mediated repression of the IL2 promoter. Multi-parameter flow cytometry analyses of patient peripheral blood mononuclear cells revealed strongly impaired natural killer cell differentiation and function, and increased CD8⁺ T cell activation and cytokine secretion. Strikingly, patient CD4⁺ T cells were hyperactive, produced elevated levels of nearly all T helper (T_H) cytokines, and readily proliferated in response to stimulation. Patient regulatory T cells (Tregs) developed normally but aberrantly produced high levels of many T_H cytokines. Single-cell RNA sequencing revealed largely normal Tregs (albeit mostly memory), but naïve CD4⁺ T cells that were more enriched in genes related to activation, proliferation, metabolism, and T_H differentiation. This work describes the immunological phenotype of one of the first reported cases of germline dominant negative HELIOS deficiency, expands our understanding of the pathogenesis of AIHA on a single cell level, and provides valuable insights into HELIOS function in a variety of lymphocyte subsets.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"89"},"PeriodicalIF":7.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016872","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":"Amyloidosis in Human Inborn Errors of Immunity Predicts Poor Prognosis.","authors":"Elif Soyak Aytekin, Anar Tagiyev, Onat Silleli, İncinur Samur, Fevzi Demirel, Saliha Esenboğa, Emine Arzu Sağlam, Deniz Çağdaş","doi":"10.1007/s10875-025-01875-1","DOIUrl":"https://doi.org/10.1007/s10875-025-01875-1","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic inflammation in inborn errors of immunity(IEI) caused by the infections or immune dysregulation is associated with the amyloid A (AA) amyloidosis development. This study aims to analyze the clinical characteristics, management strategies, and outcomes of patients with IEI complicated by AA amyloidosis, focusing on demographics, disease manifestations, treatment modalities, and survival rates.</p><p><strong>Methods: </strong>Thirteen patients diagnosed with IEI and AA amyloidosis, along with an additional 10 patients previously reported from Türkiye, were reviewed retrospectively.</p><p><strong>Results: </strong>The median ages at diagnosis of IEI and amyloidosis were 20 years (2-61) and 25 years (7-70), respectively. Renal (74%) and gastrointestinal involvement (44%) were the most common, followed by skin(9%), pulmonary (9%), and cardiac involvement (9%). Primary antibody deficiencies(48%), combined immunodeficiencies(31%), hyperimmunoglobulin E syndrome(9%), congenital neutropenia (4%), autoinflammatory disorders (4%), and chronic mucocutaneous candidiasis (4%) were the IEI types associated with amyloidosis. Bronchiectasis (74%) and malignancy (17%) were observed in given ratio of patients. Treatment modalities for amyloidosis include colchicine (n = 12, 52%), steroids (n = 5, 22%) and tocilizumab (n = 2, 9%) without significant benefit. Thirteen patients (57%) died with a median age of 24 years (8-45), predominantly due to sepsis (52%). Familial Mediterranean fever (FMF) gene analysis was negative in all patients except for one, who had a heterozygous MEFV gene defect (M694V).</p><p><strong>Conclusion: </strong>AA amyloidosis in IEI is associated with severe morbidity and mortality. Early diagnosis and management of IEI are crucial to prevent amyloidosis development. However, colchicine appears ineffective once amyloidosis has occurred, highlighting the need for further research into early diagnostic biomarkers and novel treatment options.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"88"},"PeriodicalIF":7.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012373","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 Description of Immunodeficiency and Immune Dysregulation in a 14-Year-Old Girl with Noonan Syndrome 13.","authors":"Saira Tabassum, Sarah Grün, Ben Molloy, Eppie Jones, Patrick G Buckley, Rebecca Amet, Anthony M McElligott, Derek G Doherty, Stephan Ehl, Timothy Ronan Leahy","doi":"10.1007/s10875-025-01881-3","DOIUrl":"https://doi.org/10.1007/s10875-025-01881-3","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"87"},"PeriodicalIF":7.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017881","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":"Safety and Diagnostic Utility of Brain Biopsy and Metagenomics in Decision-Making for Patients with Inborn Errors of Immunity (IEI) and Unexplained Neurological Manifestations.","authors":"Jesmeen Maimaris, Julia Payne, Adriel Roa-Bautista, Judith Breuer, Nathaniel Storey, Sofia Morfopoulou, Alasdair Bamford, Felice D'Arco, Kimberly Gilmour, Kristian Aquilina, Jane Hassell, Yael Hacohen, Adikarige H D Silva, Ashirwad Merve, Thomas S Jacques, Kanchan Rao, Robert Chiesa, Persis Amrolia, Juliana Silva, Helen Braggins, Jinhua Xu-Bayford, David Goldblatt, Austen Worth, Claire Booth, Winnie Ip, Waseem Qasim, Maaike Kusters, Marios Kaliakatsos, Julianne R Brown, Reem Elfeky","doi":"10.1007/s10875-025-01878-y","DOIUrl":"https://doi.org/10.1007/s10875-025-01878-y","url":null,"abstract":"<p><p>Unexplained neurological symptoms can pose a diagnostic challenge in patients with inborn errors of immunity (IEI) where the aetiology can be varied, and diverse pathologies may require contrasting treatments. Brain biopsy, the process of sampling brain tissue directly, has historically provided histological and microbiological information and can now be exploited for deep metagenomic next generation analysis (mNGS). We conducted a retrospective analysis of clinical and diagnostic data on paediatric patients with IEI who had a brain biopsy between 2010 and 2022 at a UK tertiary centre where 14 patients fulfilled our search criteria. We report on clinical characteristics, adverse events and the additional impact of mNGS of brain biopsies, where these were conducted. We found that brain biopsy enabled diagnostics with manageable complications in most cases, either by tissue or metagenomics analysis (n = 11/14, 79%). We found that mNGS analysis improved the diagnostic yield of brain biopsy in 29% of IEI cases (n = 4/14). Brain biopsy enabled a change in management in 71% of cases (n = 10/14). This series provides compelling evidence for the safe and purposeful use of brain biopsy in children with IEI.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"86"},"PeriodicalIF":7.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007893","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":"DOCK2 Deficiency and GATA2 Haploinsufficiency Can Underlie Critical Coronavirus Disease 2019 (COVID-19) Pneumonia.","authors":"Sajjad Biglari, Leila Youssefian, Mohammad Amin Tabatabaiefar, Amir Hossein Saeidian, Bahareh Abtahi-Naeini, Erfan Khorram, Roya Sherkat, Atefeh Sohanforooshan Moghaddam, Fatemeh Mohaghegh, Maziyar Rahimi, Hamid Rahimi, Sharareh Babaei, Mohammad Shahrooei, Nikoo Mozafari, Shirin Zaresharifi, Fatemeh Vahidnezhad, Vida Homayouni, Lam C Tsoi, Johann E Gudjonsson, Hakon Hakonarson, Jean-Laurent Casanova, Emmanuelle Jouanguy, Vivien Béziat, Qian Zhang, Aurélie Cobat, Hassan Vahidnezhad","doi":"10.1007/s10875-025-01877-z","DOIUrl":"10.1007/s10875-025-01877-z","url":null,"abstract":"<p><p>The life-threatening coronavirus disease 2019 (COVID-19) affects about 1 in 1,000 healthy people under 50 without underlying conditions. Among patients with critical COVID-19 pneumonia, rare germline variants at genes controlling type I IFN immunity have been reported in up to 5% of patients. Causal etiologies in 80-85% of cases are still unknown. We analyzed two families with hypoxemic COVID-19 pneumonia for known single-gene inborn errors of immunity. In Family 1, two siblings with critical COVID-19 were homozygous for a DOCK2 variant, c.3624+5G>A. DOCK2 deficiency is a known T-cell disorder underlying severe viral diseases. The variant resulted in skipping exon 35, which was predicted to produce a frameshift truncated protein (p.L1157Ifs*12). The proband showed markedly decreased blood CD4 T-helper cell counts, impaired T lymphocyte transformation test, and increased serum IgG, IgA, and IgE levels, as documented in other DOCK2-deficient patients. In Family 2, the proband had lethal COVID-19 and HPV-2-associated multiple recalcitrant warts. She was heterozygous for a deletion in GATA2:c.1075_1102del28, p.W360Sfs*18. GATA2 haploinsufficiency is a known cause of severe viral diseases due to a lack of plasmacytoid dendritic cell (pDC) development. The proband had monocytopenia and a lack of circulating pDCs, as reported in other patients with GATA2 haploinsufficiency. Overall, both DOCK2 deficiency and GATA2 haploinsufficiency are associated with critical and often fatal COVID-19 pneumonia.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"85"},"PeriodicalIF":7.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735714","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":"Multi-Year Registry Study of Elapegademase Treatment in Patients With Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) Requiring Enzyme Replacement Therapy.","authors":"Morna J Dorsey, Manish J Butte, Jay A Lieberman, Heather Lehman, Tracy Fausnight, Michael D Keller, Caroline Fradette, Michael S Hershfield, Tamara C Pozos, Anna Rozova, Luke A Wall, Jeffrey J Bednarski, Teresa K Tarrant, Hey J Chong, Bob Geng, Noemi Toiber Temin, Susan S Laubach, Leo Lin, Talal Mousallem, Jolan E Walter","doi":"10.1007/s10875-025-01873-3","DOIUrl":"10.1007/s10875-025-01873-3","url":null,"abstract":"<p><strong>Purpose: </strong>The safety and tolerability of elapegademase (elapegademase-lvlr; Revcovi^®) a PEGylated recombinant adenosine deaminase (ADA), were demonstrated in two Phase 3 clinical trials in the U.S. and Japan in patients with ADA-deficient severe combined immunodeficiency (ADA-SCID). Elapegademase replaced Adagen^® (pegademase, a PEGylated bovine ADA) in 2018. This registry study (NCT03878069) was conducted as a post-marketing requirement to bolster the limited safety and effectiveness data on elapegademase in patients with ADA-SCID and to study patients starting on enzyme replacement therapy (ERT) de novo.</p><p><strong>Methods: </strong>Patients were managed by routine clinical care and treating physicians' judgement from September 2019 to January 2023. Primary endpoints included trough plasma ADA activity and total trough erythrocyte deoxyadenosine nucleotides (dAXP). Secondary outcomes included lymphocyte counts, hospitalizations, infections, and safety outcomes.</p><p><strong>Results: </strong>Thirty-two patients were grouped as ERT-naïve (n = 7; infants and children with no prior ERT [EN]); pegademase-transitioning (n = 21; from pegademase to elapegademase [PT]); and patients who had participated in the Phase 3 clinical trial (n = 4; STP-2279-002; [STP]). The EN group maintained optimal plasma ADA activity, increased lymphocyte counts, had manageable infections, and had no mortality for up to 30 months while on elapegademase. The STP group and 66.7% of the PT group continued to maintain satisfactory levels of both ADA and dAXP with stable rates of infections and hospitalizations and stable lymphocyte counts for up to 48.6 months. Variability on all measures was seen, but overall, patients did not deteriorate while on elapegademase.</p><p><strong>Conclusion: </strong>Effectiveness of elapegademase was maintained up to 4 years of use and with no new safety concerns.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"84"},"PeriodicalIF":7.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719394","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":"Diagnosis, Characteristics, and Outcome of Selective Anti-polysaccharide Antibody Deficiencies In A Retrospective Cohort of 55 Adult Patients.","authors":"Nicolas Perrard, Sarah Stabler, Sébastien Sanges, Louis Terriou, Catherine Lamblin, Sacha Gaillard, Fanny Vuotto, Cécile Chenivesse, Geoffrey Mortuaire, Frédéric Batteux, Floriane Mirgot, Aurore Collet, Benjamin Lopez, Sylvain Dubucquoi, Myriam Labalette, Eric Hachulla, David Launay, Guillaume Lefèvre","doi":"10.1007/s10875-025-01874-2","DOIUrl":"10.1007/s10875-025-01874-2","url":null,"abstract":"<p><p>Selective anti-polysaccharide antibody deficiency (SPAD) predisposes to encapsulated bacterial infections. The diagnosis is challenging, and literature reports are scarce in adult patients, we therefore aim to describe the demographics, infectious complications, therapeutic strategies, and outcome of adult patients. We conducted a multicenter observational study involving 55 adult patients with SPAD. The median [interquartile range, IQR] age was 45 [36-60] years at diagnosis of SPAD, and 75% of patients were female. Twenty-one patients (38%) had a history of allergic and/or inflammatory disease, mainly asthma (n = 12), and rheumatic diseases (n = 6). Twelve patients (22%) were diagnosed after a single severe infection and 43 (78%) in a context of recurrent benign and/or severe infections. In the latter, the median time from first infections to diagnosis was 74.5 [33-167] months. Diagnostic delay was significantly higher in patients presenting with bronchiectasis than in those without (122 months [33-219.5] vs 24 months [14.5-74.5], p = 0.0042). In 22 patients (40%) receiving immunoglobulin replacement therapy (IgRT), the mean (min-max) frequency of antibiotic courses decreased from 7.9 (2-18) to 0.7 (0-2) courses per year (p < 0.001) with a median follow-up period of 46 [27-73] months. Patients diagnosed after a single severe infection did not have any relapse during a median follow-up of 85 [80.5-104.5] months after diagnosis. Adult patients with SPAD have allergic or inflammatory disorders which could contribute to the diagnostic delay. IgRT is effective in preventing recurrent infections. Further studies are warranted to confirm if SPAD should be considered after a first unexplained severe bacterial infection.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"82"},"PeriodicalIF":7.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648885","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":"Deficiency of Adenosine Deaminase 2 Masquerading as Behçet's Disease: Phenotypic Mimicry with HLA-B*51 Positivity.","authors":"Abdullah Almojali, Abdulrahman Alrasheed, Bushra Alharbi, Reem Alharbi, Wafaa Alsuwairi, Fayhan Alroqi, Jubran Alqanatish","doi":"10.1007/s10875-025-01876-0","DOIUrl":"10.1007/s10875-025-01876-0","url":null,"abstract":"<p><strong>Purpose: </strong>Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease resulting from biallelic loss-of-function mutations in ADA2 gene. It has variable clinical manifestations, some of which can mimic Behçet's disease (BD). Herein, we present a family of three siblings diagnosed with DADA2, two of whom were initially misdiagnosed as BD based on clinical phenotype including positive human leukocyte antigen B51 (HLA-B*51).</p><p><strong>Methods: </strong>Gene mutational analysis was performed by whole exome (WES) and Sanger sequencing.</p><p><strong>Results: </strong>We reported two siblings presented with recurrent oral ulcers, fever, arthritis, and skin lesions, alongside elevated inflammatory markers and HLA-B*51 positivity, leading to an initial misdiagnosis of BD. Genetic testing later revealed a homozygous ADA2 variant (c.139G > A p.Gly47Arg) in both siblings and their asymptomatic younger sister, confirming DADA2 diagnosis. Thereafter, we reviewed the literature to identify other patients misdiagnosed with BD but later found to have DADA2. This resulted in a cohort of 10 DADA2 patients, including our two reported siblings. The median time from symptoms onset to the final diagnosis of DADA2 was 7 years. All patients exhibited BD-like phenotype, except for uveitis, and 8 were HLA-B*51 positive, which likely contributed to the diagnostic confusion.</p><p><strong>Conclusion: </strong>These findings highlight the broad clinical spectrum of DADA2, which can resemble BD, and suggest that HLA-B*51 positivity in DADA2 may further complicate diagnosis. Clinicians should maintain a high index of suspicion for DADA2 in early-onset BD-like cases, particularly without uveitis, or a family history of similar symptoms. Further studies are warranted to explore HLA-B*51 role in DADA2 phenotype.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"83"},"PeriodicalIF":7.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648883","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}