Journal of Clinical Immunology最新文献

{"title":"Genetic Characteristics of a Large Pediatric Cohort of Patients with Inborn Errors of Immunity: Single-Center Experience.","authors":"Natalia Kuzmenko, Maxim Alexenko, Anna Mukhina, Yulia Rodina, Mariia Fadeeva, Dmitrii Pershin, Amina Kieva, Elena Raykina, Miсhael Maschan, Galina Novichkova, Anna Shcherbina","doi":"10.1007/s10875-024-01767-w","DOIUrl":"10.1007/s10875-024-01767-w","url":null,"abstract":"<p><p>More than 450 genetic defects result in inborn errors of immunity (IEI). Their individual prevalence in specific cohorts is influenced by national characteristics and other factors. We present results of genetic testing conducted in 1809 Russian children with IEI. Genetic defects confirming IEI were found in 1112 out of 1809 (61.5%) probands. These defects included variants in 118 single genes (87.9% of patients) and aberrations in 6 chromosomes (11.8%). Notably, three patients harbored pathogenic variants in more than one IEI gene. Large deletions constituted 5% of all defects. Out of the 799 original variants, 350 (44%) have not been described previously. Rare genetic defects (10 or fewer patients per gene) were identified in 20% of the patients. Among 967 probands with germline variants, defects were inherited in an autosomal dominant manner in 29%, X-linked in 34%, and autosomal recessive in 37%. Four females with non-random X-inactivation exhibited symptoms of X-linked diseases (BTK, WAS, CYBB, IKBKG gene defects). Despite a relatively low rate of consanguinity in Russia, 47.9% of autosomal recessive gene defects were found in a homozygous state. Notably, 28% of these cases carried \"Slavic\" mutation of the NBN gene or known hot-spot mutations in other genes. The diversity of IEI genetic forms and the high frequency of newly described variants underscore the genetic heterogeneity within the Russian IEI group. The new variants identified in this extensive cohort will enrich genetic databases.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"165"},"PeriodicalIF":7.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies Neutralizing GM-CSF in HIV-Negative Colombian Patients Infected with Cryptococcus gattii and C. neoformans.","authors":"Carlos A Arango-Franco, Julian Rojas, Carolina Firacative, Mélanie Migaud, Clara Inés Agudelo, José Luis Franco, Jean-Laurent Casanova, Anne Puel, Jairo Lizarazo, Elizabeth Castañeda, Andrés A Arias","doi":"10.1007/s10875-024-01757-y","DOIUrl":"10.1007/s10875-024-01757-y","url":null,"abstract":"<p><strong>Background: </strong>Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016.</p><p><strong>Methods: </strong>We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans).</p><p><strong>Results: </strong>We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans.</p><p><strong>Conclusions: </strong>We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"163"},"PeriodicalIF":7.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616579","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":"Omenn Syndrome can Occur during Enzyme Therapy for Adenosine Deaminase Deficiency.","authors":"Elizabeth M Forbes, Peter B McNaughton","doi":"10.1007/s10875-024-01764-z","DOIUrl":"10.1007/s10875-024-01764-z","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"162"},"PeriodicalIF":7.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<ArticleTitle xmlns:ns0=\"http://www.w3.org/1998/Math/MathML\">Prevalence of Anti-Interferon <ns0:math><ns0:mi>α</ns0:mi></ns0:math> Auto-Antibodies in Patients with Antibody Deficiency.","authors":"Douglas L Fink, Orest Idilli, Adrian Shields, Alex Richter, Siobhan O Burns","doi":"10.1007/s10875-024-01761-2","DOIUrl":"10.1007/s10875-024-01761-2","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"161"},"PeriodicalIF":7.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review.","authors":"Nazanin Fathi, Matineh Nirouei, Zahra Salimian Rizi, Saba Fekrvand, Hassan Abolhassani, Fereshte Salami, Arsh Haj Mohamad Ebrahim Ketabforoush, Gholamreza Azizi, Amene Saghazadeh, Marzie Esmaeili, Amir Almasi-Hashiani, Nima Rezaei","doi":"10.1007/s10875-024-01763-0","DOIUrl":"10.1007/s10875-024-01763-0","url":null,"abstract":"<p><strong>Background: </strong>Inborn errors of immunity (IEIs) encompass various diseases with diverse clinical and immunological symptoms. Determining the genotype-phenotype of different variants in IEI entity precisely is challenging, as manifestations can be heterogeneous even in patients with the same mutated gene.</p><p><strong>Objective: </strong>In the present study, we conducted a systematic review of patients recorded with NFKB1 and NFKB2 mutations, two of the most frequent monogenic IEIs.</p><p><strong>Methods: </strong>The search for relevant literature was conducted in databases including Web of Science, PubMed, and Scopus. Information encompassing demographic, clinical, immunological, and genetic data was extracted from cases reported with mutations in NFKB1 and NFKB2. The comprehensive features of manifestations in patients were described, and a comparative analysis of primary characteristics was conducted between individuals with NFKB1 loss of function (LOF) and NFKB2 (p52-LOF/IκBδ-gain of function (GOF)) variants.</p><p><strong>Results: </strong>A total of 397 patients were included in this study, 257 had NFKB1 mutations and 140 had NFKB2 mutations. There were 175 LOF cases in NFKB1 and 122 p52^LOF/IκBδ^GOF cases in NFKB2 pivotal groups with confirmed functional implications. NFKB1LOF and p52^LOF/IκBδ^GOF predominant cases (81.8% and 62.5% respectively) initially presented with a CVID-like phenotype. Patients with NFKB1LOF variants often experienced hematologic autoimmune disorders, whereas p52^LOF/IκBδ^GOF patients were more susceptible to other autoimmune diseases. Viral infections were markedly higher in p52^LOF/IκBδ^GOF cases compared to NFKB1LOF (P-value < 0.001). NFKB2 (p52^LOF/IκBδ^GOF) patients exhibited a greater prevalence of ectodermal dysplasia and pituitary gland involvement than NFKB1LOF patients. Most NFKB1LOF and p52^LOF/IκBδ^GOF cases showed low CD19 + B cells, with p52^LOF/IκBδ^GOF having more cases of this type. Low memory B cells were more common in p52^LOF/IκBδ^GOF patients.</p><p><strong>Conclusions: </strong>Patients with NFKB2 mutations, particularly p52^LOF/IκBδ^GOF, are at higher risk of viral infections, pituitary gland involvement, and ectodermal dysplasia compared to patients with NFKB1LOF mutations. Genetic testing is essential to resolve the initial complexity and confusion surrounding clinical and immunological features. Emphasizing the significance of functional assays in determining the probability of correlations between mutations and immunological and clinical characteristics of patients is crucial.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"160"},"PeriodicalIF":7.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rubella virus-associated granulomas controlled with allogeneic hematopoietic stem cell transplantation.","authors":"Timo Hautala, Ludmila Perelygina, Urpu Salmenniemi, Mikko R J Seppänen","doi":"10.1007/s10875-024-01756-z","DOIUrl":"10.1007/s10875-024-01756-z","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"159"},"PeriodicalIF":7.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498195","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: Successful Immune Reconstitution in a Patient with a TYK2 Deficiency after Allogeneic Stem Cell Transplantation from Unrelated Donors.","authors":"Yelei Gao, Ya Wang, Lina Zhou, Ge Lv, Jie Yu, Luying Zhang, Yan Meng, Wenli He, Ran Chen, Xiaodong Zhao, Ying Dou","doi":"10.1007/s10875-024-01762-1","DOIUrl":"10.1007/s10875-024-01762-1","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"158"},"PeriodicalIF":7.2,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye.","authors":"Baran Erman, Umran Aba, Canberk Ipsir, Damla Pehlivan, Caner Aytekin, Gökhan Cildir, Begum Cicek, Ceren Bozkurt, Sidem Tekeoglu, Melisa Kaya, Cigdem Aydogmus, Funda Cipe, Gulsan Sucak, Sevgi Bilgic Eltan, Ahmet Ozen, Safa Barıs, Elif Karakoc-Aydiner, Ayca Kıykım, Betul Karaatmaca, Hulya Kose, Dilara Fatma Kocacık Uygun, Fatih Celmeli, Tugba Arikoglu, Dilek Ozcan, Ozlem Keskin, Elif Arık, Elif Soyak Aytekin, Mahmut Cesur, Ercan Kucukosmanoglu, Mehmet Kılıc, Mutlu Yuksek, Zafer Bıcakcı, Saliha Esenboga, Deniz Çagdaş Ayvaz, Asena Pınar Sefer, Sukrü Nail Guner, Sevgi Keles, Ismail Reisli, Ugur Musabak, Nazlı Deveci Demirbas, Sule Haskologlu, Sara Sebnem Kilic, Ayse Metin, Figen Dogu, Aydan Ikinciogulları, Ilhan Tezcan","doi":"10.1007/s10875-024-01759-w","DOIUrl":"10.1007/s10875-024-01759-w","url":null,"abstract":"<p><p>Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients' long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"157"},"PeriodicalIF":7.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492188","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":"Lymphocyte-Directed Immunomodulation Remits Thymoma-Associated Autoimmune Pneumonitis.","authors":"Elise M N Ferré, Diana X Nichols-Vinueza, Lindsey B Rosen, Peter D Burbelo, Kevin P Fennelly, Joseph Pechacek, Daniel M Goldstein, Anahita Agharahimi, Annapurna Saksena, David E Kleiner, Yesim Yilmaz Demirdag, Arun Rajan, David S Schrump, Steven M Holland, Alexandra F Freeman, Michail S Lionakis","doi":"10.1007/s10875-024-01760-3","DOIUrl":"10.1007/s10875-024-01760-3","url":null,"abstract":"<p><strong>Background: </strong>Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome.</p><p><strong>Objectives: </strong>To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation.</p><p><strong>Methods: </strong>Two patients with thymoma were enrolled on IRB-approved protocols at the NIH Clinical Center. We performed history and physical examination; laboratory, radiographic, histologic and pulmonary function evaluations; and measurement of the lung-directed autoantibodies KCNRG and BPIFB1 prior to and at 1- and 6-months following initiation of lymphocyte-directed immunomodulation with azathioprine with or without rituximab.</p><p><strong>Results: </strong>Combination T- and B-lymphocyte-directed immunomodulation resulted in improvement of clinical, functional, and radiographic parameters at 6-month follow-up evaluations in both patients with sustained remission up to 12-36 months following treatment initiation.</p><p><strong>Conclusion: </strong>Lymphocyte-directed immunomodulation remitted autoimmune pneumonitis in two patients with thymoma.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"156"},"PeriodicalIF":7.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492189","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 Mutation in the Moesin (MSN) Gene Leads to Immunodeficiency with Epstein-Barr Virus (EBV) Infection and Dermatomyositis-Like Symptoms.","authors":"Bijun Sun, Luyao Liu, Lingli Han, Qifan Li, Qi Wu, Jia Hou, Wenjie Wang, Wenjing Ying, Qinhua Zhou, Feng Qian, Wei Lu, Xiaochuan Wang, Jinqiao Sun","doi":"10.1007/s10875-024-01755-0","DOIUrl":"10.1007/s10875-024-01755-0","url":null,"abstract":"<p><strong>Purpose: </strong>Moesin (MSN) deficiency is a recently reported combined immunodeficiency, and few cases have been reported to date. We describe a Chinese patient with a novel mutation causing MSN deficiency and a novel phenotype.</p><p><strong>Methods: </strong>Clinical and immunological data were collected. Whole-exome sequencing was performed to identify gene mutations. MSN protein expression and T cell proliferation and activation were determined by flow cytometry. Cell migration was confirmed with a Transwell assay. Autoantibody levels were analyzed using antigen microarrays.</p><p><strong>Results: </strong>The patient was a 10-year-old boy who presented with recurrent fever, oral ulcers and dermatomyositis-like symptoms, such as periorbital edema, facial swelling, elevated creatine kinase levels, and abnormal electromyography and muscle biopsy results. Epstein-Barr virus (EBV) DNA was detected in the serum, cells and tissues of this patient. He further developed nasal-type NK/T-cell lymphoma. A novel hemizygous mutation (c.68 A > G, p.N23S) in the MSN gene was found. The immunological phenotype of this patient included persistent decreases in T and B lymphocyte counts but normal immunoglobulin IgG levels. The patient had attenuated MSN protein expression and impaired T-cell proliferation and migration. The proportions of Tfh cells and CD21^low B cells in the patient were higher than those in the controls. Moreover, 82 IgG and 102 IgM autoantibodies were more abundant in the patient than in the healthy controls.</p><p><strong>Conclusions: </strong>The novel mutation N23S is pathogenic and leads to a severe clinical phenotype. EBV infection, tumor, and dermatomyositis-like autoimmune symptoms may be associated with MSN deficiency, further expanding the understanding of the disease.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"155"},"PeriodicalIF":7.2,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}