Journal of Clinical Immunology最新文献

{"title":"Chronic Kidney Disease in Common Variable Immunodeficiency: a Multicenter Study.","authors":"Chiara De Renzis, Renato Finco Gambier, Antonietta Gigante, Carla Maria Deiana, Gianluca Lagnese, Lorenzo Gatti, Giulia Garzi, Giulia Costanzo, Chiara Pagnozzi, Stefania Nicola, Luisa Brussino, Giuseppe Spadaro, Marcello Rattazzi, Davide Firinu, Francesco Cinetto, Cinzia Milito","doi":"10.1007/s10875-025-01890-2","DOIUrl":"10.1007/s10875-025-01890-2","url":null,"abstract":"<p><strong>Purpose: </strong>There are few reports of renal involvement in Common Variable Immunodeficiencies (CVID) and, when present, is due to infections, inflammation, or treatments. The aim of this study was evaluating the prevalence of chronic kidney disease (CKD) and to identify CVID-related clinical, laboratory and therapeutic features inducing it.</p><p><strong>Methods: </strong>A multicenter observational retrospective study on 367 adult CVID patients from five Italian Referral Centers for Primary Immunodeficiency.</p><p><strong>Results: </strong>CKD was identified in 23 (6.27%) patients that were older (p < 0.001), had arterial hypertension (p < 0.001), diabetes (p = 0.002), dyslipidemia (p = 0.002), presented different ultrasound abnormalities (p < 0.001) and received predominantly intravenous immunoglobulins (IVIG) (p = 0.016). Regarding CVID infectious and non-infectious manifestations, CKD patients presented a higher frequency of COPD (p = 0.008). In the CKD group, the median absolute count of total lymphocytes (p = 0.015), the percentage of total B (p = 0.028) and transitional B cells (p = 0.008) were lower. By binomial logistic regression analysis adjusted for age, CKD patients tend to develop autoimmune cytopenia, had lower B cells percentage, increased Neutrophil-to-lymphocyte ratio and received more frequently trimethoprim-sulfamethoxazole antibiotic prophylaxis. By multivariate analysis, only autoimmune cytopenia was independently associated with CKD.</p><p><strong>Conclusion: </strong>The prevalence of CKD in CVID is due to aging, age-related comorbidities, disease-related immune dysregulation and inflammation. Our results suggest evaluating renal function in all CVID patients, and mostly in those with a higher \"inflammatory\" burden.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"97"},"PeriodicalIF":7.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127760","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: Pre-Transplant Immune Dysregulation Predicts for Poor Outcome Following Allogeneic Haematopoietic Stem Cell Transplantation in Adolescents and Adults with Inborn Errors of Immunity (IEI).","authors":"Thomas A Fox, Valerie Massey, Charley Lever, Rachel Pearce, Arian Laurence, Sarah Grace, Filippo Oliviero, Sarita Workman, Andrew Symes, David M Lowe, Valeria Fiaccadori, Rachael Hough, Susan Tadros, Siobhan O Burns, Markus G Seidel, Ben Carpenter, Emma C Morris","doi":"10.1007/s10875-025-01893-z","DOIUrl":"10.1007/s10875-025-01893-z","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"95"},"PeriodicalIF":7.2,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078255","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":"Newborn Screening Followed By Early Treatment is Essential to Improve Survival in SCID.","authors":"Gabriela Assunção Goebel, Luciana Araújo Oliveira Cunha, Fernanda Gontijo Minafra, Jorge Andrade Pinto","doi":"10.1007/s10875-025-01887-x","DOIUrl":"10.1007/s10875-025-01887-x","url":null,"abstract":"<p><p>Severe combined immunodeficiency (SCID) is a heterogeneous genetic disease characterized by severe T-cell lymphopenia with a profound impairment of T- and B-cells' function and, in some types, also NK cells. Hematopoietic cell transplantation (HCT) is the only curative treatment currently available in Brazil. Late diagnosis and treatment are the main factors affecting the survival of these children. This study aims to describe the demographic, phenotypic, genotypic, and clinical characteristics of twenty SCID patients (including typical SCID, leaky-SCID, and Omenn Syndrome) followed at a Brazilian referral center and correlate these data with their clinical outcome. The children were analyzed into two groups: patients diagnosed early by newborn screening (NBS) or family history, n = 7, and patients with late diagnosis, by clinical presentation, n = 13. The 2-year overall survival (OS) of the late group was 29.2%, in contrast to the 2-year OS of the early diagnosis group of 71.4% (p = 0.053). However, despite early diagnosis in the first group, timely access to HCT was delayed, with a median of 11 months. This research reveals that survival depends not only on timely diagnosis but also on early definitive treatment. To improve SCID survival rates, developing countries need public policies that allow rapid access to curative treatment for these patients.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"94"},"PeriodicalIF":7.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078308","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":"Deepening Understanding of the Clinical Features and Diagnostic Approaches to Anti-Interferon-Gamma Autoantibody Associated Adult-Onset Immunodeficiency in the Last 20 Years: A Case Report and Literature Review.","authors":"Liyan Zhao, Jindi Ma, Ying Sun, Xiaopeng Yu, Yingfeng Lu, Haijiang Qian, Ren Yan, Yimin Zhang","doi":"10.1007/s10875-025-01885-z","DOIUrl":"10.1007/s10875-025-01885-z","url":null,"abstract":"<p><p>Anti-interferon-gamma autoantibody (AIGA)-associated adult-onset immunodeficiency (AOID) is an emerging disease that can lead to serious opportunistic infections, which has a history of 20 years since it was first reported in 2004. It's a hard-detected AOID caused by AIGA. In recent years, there has been an increasing number of reports on the disease, but there is still a lack of consensus on the diagnosis and treatment. We here report a case of a 70-year-old Chinese male who had had AIGA in serum and suffered from recurrent pyothorax. Although his condition improved with antimicrobial therapy each time, his pyothorax frequently relapsed, requiring repeated hospitalizations. A literature review of AIGA-associated AOID was conducted. We searched PubMed, Web of Science, Embase, and the Chinese literature database for manuscripts concerning AIGA. Cases detected with AIGA and met our criteria were included. A total of 502 patients were retrospectively analyzed, with 256 (51.0%) males and 246 (49.0%) females. The majority of patients are from Southeast Asia (98.2%). Lymph node (83.7%) is the most commonly involved organ, followed by the lung (60.6%). Nontuberculous mycobacteria (NTM) was identified as the predominant pathogen reported in 77.49% of the patients. The clinical manifestations are diverse and non-specific for the disease often presenting with multi-organ involvement and multiple infections. Timely identification of patients with AIGA, appropriate diagnosis, and individualized treatment are critical; thus, we propose a reasonable diagnostic criterion and a structured diagnostic and treatment process based on our findings to provide clinicians with comprehensive information for clinical practice.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"93"},"PeriodicalIF":7.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009754","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":"Prevalence of Ophthalmological Manifestations in Patients with Inborn Errors of Immunity: A Systematic Review and Meta-Analysis.","authors":"Laura Zárate-Pinzón, Germán Mejía-Salgado, Carlos Cifuentes-González, Oscar Correa-Jiménez, Stefania Amaris, Alberto Alfaro-Murillo, Juanita Téllez-Zambrano, Angie Verbel, Paula Monje-Tobar, Alejandra de-la-Torre","doi":"10.1007/s10875-025-01880-4","DOIUrl":"10.1007/s10875-025-01880-4","url":null,"abstract":"<p><strong>Background: </strong>Although some reports indicate ocular involvement in Inborn Errors of Immunity (IEI) patients, the characteristics of this association remain unclear. Increased awareness can facilitate early diagnosis and prevention of visual complications.</p><p><strong>Objective: </strong>To determine the prevalence and characterize ophthalmological manifestations in patients with IEI.</p><p><strong>Methods: </strong>A systematic literature search was performed across Embase, PubMed, and Lilacs. Observational studies with at least 10 IEI patients exhibiting ophthalmological manifestations were reviewed. A meta-analysis using a random effects model, weighted proportion, and 95% confidence intervals were reported as appropriate.</p><p><strong>Results: </strong>Sixty-two articles out of the 6,884 studies were included. The pooled prevalence of ocular manifestations in IEI patients was 54% (95%CI = 39-69), with a mean age of 11.1 ± 7.8 years and male predominance. Regarding the type of IEI with ocular involvement, the most frequently affected group was the Combined immunodeficiencies with associated or syndromic features (82%, 95%CI = 66-91), followed by the diseases of immune dysregulation (73%, 95%CI = 27-95), auto-inflammatory disorders (48%, 95%CI = 10-88), and congenital defects of phagocytes (39%, 95%CI = 11-76). Europe had the highest prevalence of patients with ocular manifestations (68%, 95%CI = 32-90). The most common ocular manifestations observed in IEI patients were those affecting ocular mobility, followed by those that involved the anterior segment, posterior segment, eyelids, and adnexal structures.</p><p><strong>Conclusions: </strong>These results highlight a significant burden of ocular involvement in IEI patients, mainly during childhood and associated with amblyogenic factors. Therefore, ophthalmologists, pediatricians, and immunologists must be involved in early detection to prevent ocular complications and overall well-being.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"92"},"PeriodicalIF":7.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007750","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":"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}