Journal of Clinical Immunology最新文献

{"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}

{"title":"Efficacy, Safety, Tolerability, and Serum IgG Trough Levels of Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% in US Pediatric Patients with Primary Immunodeficiency Diseases.","authors":"Niraj C Patel, Jolan E Walter, Richard L Wasserman, Arye Rubinstein, Suthida Kankirawatana, Meagan W Shepherd, Erin Greco, Zhaoyang Li, Sharon Russo-Schwarzbaum, Shumyla Saeed-Khawaja, Barbara McCoy, Leman Yel","doi":"10.1007/s10875-025-01862-6","DOIUrl":"10.1007/s10875-025-01862-6","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the efficacy, safety, tolerability, and serum IgG trough levels of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% in US pediatric patients with primary immunodeficiency diseases (PIDDs).</p><p><strong>Methods: </strong>This phase 3, open-label, prospective study (NCT03277313) was conducted at 17 US centers. Eligible patients aged 2 to < 16 years had PIDDs and had received immunoglobulin G (IgG) at a consistent dose for ≥ 3 months before screening. Participants received fSCIG 10% via dose ramp-up for up to 6 weeks (Epoch 1), then every 3-4 weeks for ≤ 3 years (Epoch 2). The primary endpoint was the rate of acute serious bacterial infections (ASBIs).</p><p><strong>Results: </strong>Data were provided by 44 participants for Epoch 1 (mean ± SD age: 9.0 ± 3.6 years) and 43 (97.7%) for Epoch 2; 34 (77.3%) completed the study. Two ASBIs (both bacterial pneumonia) were reported in one participant with specific antibody deficiency. The mean rate of ASBIs was 0.04 events/participant-year (99% upper confidence interval limit: 0.20), significantly lower than the regulatory-defined threshold of 1.0 (p < 0.001). The mean rate of all infections was 3.12 events/participant-year. Stable mean serum IgG trough levels were maintained during Epoch 2 (10.4, 9.2, and 9.2 g/L at Months 0, 6, and 12, respectively). Most related treatment-emergent adverse events were mild or moderate in severity. No participant developed anti-recombinant human hyaluronidase neutralizing antibodies; 1/44 participants (2.3%) developed binding antibodies.</p><p><strong>Conclusion: </strong>fSCIG 10% effectively prevented ASBIs in pediatric patients with PIDDs, with a favorable safety profile consistent with previous clinical studies.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"81"},"PeriodicalIF":7.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630592","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":"No Association Between HLH-associated Gene Variants and Life-Threatening COVID-19.","authors":"Laura E Covill, Aurélie Cobat, Qian Zhang, Yenan T Bryceson","doi":"10.1007/s10875-025-01870-6","DOIUrl":"10.1007/s10875-025-01870-6","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"80"},"PeriodicalIF":7.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604845","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":"Clinical Characteristics and Outcomes of Pediatric Cases Presenting with Possible Pulmonary Vasculitis Following COVID-19 Infection.","authors":"Xiaoyan Zhang, Yuhong Guan, Weihan Xu, Shunying Zhao, Haiming Yang","doi":"10.1007/s10875-025-01868-0","DOIUrl":"10.1007/s10875-025-01868-0","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"79"},"PeriodicalIF":7.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515840","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":"Successful Treatment with Sirolimus of a Patient with a Novel CARD11 Germline Mutation in B-Cell Expansion with Nuclear Factor Kappa B and T-Cell Anergy: Case Report and Literature Review.","authors":"Tsubasa Nishinosono, Hideki Muramatsu, Manabu Wakamatsu, Daiki Yamashita, Tatsuya Fukasawa, Yuichi Shirakawa, Daichi Sajiki, Ryo Maemura, Yusuke Tsumura, Ayako Yamamori, Kotaro Narita, Shinsuke Kataoka, Atsushi Narita, Nobuhiro Nishio, Yuji Miyajima, Yoshiyuki Takahashi","doi":"10.1007/s10875-025-01872-4","DOIUrl":"10.1007/s10875-025-01872-4","url":null,"abstract":"<p><strong>Purpose: </strong>B-cell expansion with nuclear factor kappa B and T-cell anergy (BENTA) is an inborn error of immunity characterized by congenital polyclonal B-cell lymphocyte expansion. In this report, we present a case of a girl diagnosed with BENTA carrying a novel CARD11 germline mutation, aiming to clarify the clinical presentation of BENTA by conducting a literature review.</p><p><strong>Methods: </strong>Genetic analysis, including whole-exome sequencing, was performed using genomic DNA extracted from the patient's peripheral blood, oral mucosa, and fingernails. Additionally, a comprehensive literature review of cases with BENTA was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.</p><p><strong>Results: </strong>A p.Leu251Pro germline variant in the CARD11 gene was identified in an 18-month-old girl with a genetic diagnosis of BENTA. She required adenoidectomy and tonsillectomy due to airway obstruction causing wheezing. Her symptoms improved with prednisolone and sirolimus. The literature review we conducted identified a total of 34 cases of BENTA. Among these cases, 15 were either asymptomatic or showed improvement without requiring any specific treatment. However, all six reported deaths were diagnosed before the age of 3 years, with two attributed to refractory hemophagocytic syndrome and four caused by opportunistic infections.</p><p><strong>Conclusion: </strong>We present a case of BENTA with life-threatening respiratory symptoms caused by a novel CARD11 germline mutation. The patient showed a positive response to immunosuppressive therapy, including sirolimus. While BENTA is typically regarded as a benign disorder, a literature review revealed that infants with BENTA are at high risk of severe outcomes and require therapeutic intervention.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"78"},"PeriodicalIF":7.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492232","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":"Bone Marrow CD8 + Abundance Inversely Correlates with Progressive Marrow Fibrosis and Myelodysplastic Evolution in GATA2 Deficiency: Case Report.","authors":"Francesca Vendemini, Samuele Roncareggi, Vincenzo L'Imperio, Fabiola Guerra, Federica Mottadelli, Marco Chiarini, Oscar Maglia, Simona Sala, Grazia Fazio, Rocco Piazza, Sonia Bonanomi, Andrea Biondi, Francesco Saettini","doi":"10.1007/s10875-025-01871-5","DOIUrl":"10.1007/s10875-025-01871-5","url":null,"abstract":"<p><strong>Purpose: </strong>GATA2 deficiency, a rare inborn error of immunity, presents with highly variable phenotypes. Bone marrow (BM) changes such as hypocellularity and myelodysplastic syndrome (MDS) are common, with hematopoietic stem cell transplantation being the only curative option due to the risk of progression to acute myeloid leukemia. Although traditional markers like cytogenetic abnormalities and somatic mutations (e.g., ASXL1) identify the risk of leukemic transformation, efforts to identify novel predictors of disease evolution are needed. CD8+ T cells are known to play a key role in MDS immune surveillance, but their specific involvement in GATA2 deficiency remains poorly defined.</p><p><strong>Methods: </strong>In this case report, we report on a young adult with GATA2 deficiency who underwent longitudinal monitoring of both peripheral and BM lymphocyte subsets, with a focus on CD8+ T-cell evolution in relation to MDS progression.</p><p><strong>Results: </strong>The patient exhibited typical GATA2-deficient immune-hematological findings, including monocytopenia, B- and NK-cell deficiency, but had no history of severe infections and remained transfusion-independent. While peripheral CD8+ T-cell levels remained stable over time, a notable reduction in BM CD8+ T cells was observed in association with MDS progression.</p><p><strong>Conclusion: </strong>Providing a long-term follow-up of one GATA2-deficient patient, we suggest that a decrease in BM CD8+ T cells may serve as an early marker of immune surveillance escape and disease progression. These findings underscore the need for further investigation into the role of BM CD8+ T cells in GATA2 deficiency and MDS evolution, potentially offering new insights for follow-up and therapeutic intervention.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"77"},"PeriodicalIF":7.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458258","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":"X-linked Deficiency in ELF4 in Females with Skewed X Chromosome Inactivation.","authors":"Rongtao Zhao, Zhuo Zhang, Shiyue Mei, Li Sun, Qianlu Zhang, Qianying Lv, Fang Zhou, Gan Sun, Lina Zhou, Xuemei Tang, Yunfei An, Zhifeng Liu, Xiaodong Zhao, Hongqiang Du","doi":"10.1007/s10875-025-01866-2","DOIUrl":"10.1007/s10875-025-01866-2","url":null,"abstract":"<p><p>Deficiency in ELF4, X-linked (DEX) is a newly identified monogenic autoinflammatory disease. Most reported cases are male, leading to the recognition of DEX being primarily limited to male patients. Here we described 3 pediatric female patients with DEX from 3 unrelated families, who are all heterozygous for ELF4 mutations (c.320_c.321insA, c.329delA and c.685 A > G). Similar to reported male DEX patients, the main clinical features include recurring oral ulcers, abdominal pain and diarrhea with colonoscopy showing ulcers in the colon. Meanwhile, novel and effective treatment strategies, such as the use of the biologic vedolizumab and exclusive enteral nutrition (EEN), have provided additional options for the treatment of DEX. Finally, we observed skewed X chromosome inactivation patterns in all three female patients, with over-inactivation of the X chromosome carrying the wild-type allele confirmed in two of them.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"76"},"PeriodicalIF":7.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458259","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}