Journal of Clinical Immunology最新文献

{"title":"Interstitial Lung Disease in a Girl with Prolidase Deficiency.","authors":"Chunna Xu, Lei Zhang, Yu Tang, Haiming Yang, Yuelin Shen","doi":"10.1007/s10875-025-01861-7","DOIUrl":"10.1007/s10875-025-01861-7","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"71"},"PeriodicalIF":7.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189317","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: Anifrolumab in Monogenic Lupus caused by TREX1 Mutation.","authors":"Patricia Moran-Alvarez, Virginia Messia, Valentina Matteo, Francesca Soscia, Giusi Prencipe, Fabrizio De Benedetti, Antonella Insalaco","doi":"10.1007/s10875-025-01864-4","DOIUrl":"10.1007/s10875-025-01864-4","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"70"},"PeriodicalIF":7.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080220","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: Quantifying the Diagnostic Odyssey Burden Among Persons with Inborn Errors of Immunity.","authors":"Sarina Nikzad, Rebekah Johnson, Christopher Scalchunes, Nicholas L Rider","doi":"10.1007/s10875-025-01859-1","DOIUrl":"10.1007/s10875-025-01859-1","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"69"},"PeriodicalIF":7.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059234","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":"Hematopoietic Stem Cell Transplantation Corrects IL-2Rβ Deficiency.","authors":"Fai AlQahtani, Manar AlGhamdi, Mofareh AlZahrani, Anas M AlAzami, Sultan Al-Buhairi, Hamoud Al-Mousa","doi":"10.1007/s10875-025-01860-8","DOIUrl":"10.1007/s10875-025-01860-8","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"68"},"PeriodicalIF":7.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046472","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":"ATM Expression and Activation in Ataxia Telangiectasia Patients with and without Class Switch Recombination Defects.","authors":"Fereshte Salami, Tannaz Moeini Shad, Nazanin Fathi, Hanieh Mojtahedi, Marzie Esmaeili, Sepideh Shahkarami, Ladan Gol Mohammad Pour Afrakoti, Parisa Amirifar, Samaneh Delavari, Hassan Nosrati, Azadehsadat Razavi, Mohammad Reza Ranjouri, Mahsa Yousefpour, Zahra Hamidi Esfahani, Gholamreza Azizi, Mahmoudreza Ashrafi, Nima Rezaei, Reza Yazdani, Hassan Abolhassani","doi":"10.1007/s10875-025-01857-3","DOIUrl":"10.1007/s10875-025-01857-3","url":null,"abstract":"<p><strong>Background: </strong>Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.</p><p><strong>Methods: </strong>A-T patients with defined genetic diagnoses were classified based on CSR and based on the severity of their medical complications. Isolated peripheral blood mononuclear cells from any patient were evaluated before and after exposure to 0.5 Gy ionizing radiation for one minute. Western blotting was performed to identify the expression of ATM and phosphorylated ATM (p-ATM) proteins compared to age-sex-matched healthy controls.</p><p><strong>Results: </strong>In severe A-T patients (n = 6), the majority (66.7%) had frameshift mutations, while 33.3% had nonsense mutations in the ATM gene. The mild group (n = 3) had two cases of splice errors and one missense mutation. All patients with CSR defect had elevated IgM serum levels, whereas all switched immunoglobulins were reduced in them. Expression of ATM and p-ATM proteins was significantly lower (p = 0.01) in all patients compared to healthy controls, both pre-and post- and post-radiation. Additionally, low ATM and p-ATM protein expression levels were linked with the clinical severity of patients but were not correlated with CSR defects.</p><p><strong>Conclusion: </strong>Expression and activation of ATM protein were defective in A-T patients compared to healthy controls. Altered expression of ATM and p-ATM proteins may have potential clinical implications for prognostic evaluation and symptom severity assessment in individuals with A-T.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"67"},"PeriodicalIF":7.2,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032863","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":"Hypomorphic RAG2 Deficiency Promotes Selection of Self-Reactive B Cells.","authors":"Christopher D Thouvenel, Christopher M Tipton, Yasuhiro Yamazaki, Ting-Ting Zhang, Stacey Rylaarsdam, Jennifer R Hom, Catherine Snead, Chengsong Zhu, Quan-Zhen Li, Yu Nee Lee, Tomoki Kawai, Neshatul Haque, Michael T Zimmermann, Sivasankaran Munusamy Ponnan, Shaun W Jackson, Rich G James, Ignacio Sanz, Luigi D Notarangelo, Troy R Torgerson, Hans D Ochs, David J Rawlings, Eric J Allenspach","doi":"10.1007/s10875-024-01849-9","DOIUrl":"10.1007/s10875-024-01849-9","url":null,"abstract":"<p><p>Reduced function or hypomorphic variants in recombination-activating genes (RAG) 1 or 2 result in a broad clinical phenotype including common variable immunodeficiency (CVID) and even adult-onset disease. Milder RAG variants are less characterized. Here we describe the longitudinal course of a milder combined RAG deficiency in 3 of 7 siblings sharing the same RAG2 mutations over a 50-year study. Whole-genome and repertoire sequencing, bacteriophage immunizations, and deep immunophenotyping were used to compare affected and unaffected family members. The clinical phenotype of three affected siblings with hypomorphic RAG deficiency ranged from combined immunodeficiency and early mortality to a late-onset CID with hyper-IgM phenotype. T cells were remarkably similar across affected siblings, yet CDR3 skewing and regulatory T cell defects were not observed. B cell analysis showed elevated unswitched CD27+ and CD21^low cells as well as features of an autoreactive antibody repertoire and presence of secreted autoantibodies, yet no clinical autoimmunity was present. Most striking was an expanded polyclonal marginal zone-like B cell population (IgM+IgD+CD27+) utilizing the self-reactive unmutated VH4-34 receptor demonstrating that hypomorphic RAG deficiency can promote expansion of self-reactive B cells. This process, however, was not sufficient to trigger clinical autoimmunity. Utilizing multiple approaches, we functionally measured the specific RAG2 variant effects and assessed how selection and secondary triggers altered the BCR repertoire and immunophenotype overtime. Overall, we demonstrate a broad disease spectrum in siblings with identical hypomorphic RAG deficiency, highlighting that phenotypic divergence can result from expansion of IgM + memory B cells.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"66"},"PeriodicalIF":7.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056032","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":"Outcomes of Hematopoietic Stem Cell Transplantation in 5 Patients with Autosomal Recessive RIPK1-Deficiency.","authors":"Rebecca B Walsh, Peter McNaughton, Zohreh Nademi, Alexandra Laberko, Dmitry Balashov, Hamoud Al-Mousa, Peter D Arkwright, Robert F Wynn, Terry Flood, Eleri Williams, Andrew Cant, Mario Abinun, Sophie Hambleton, Mary Slatter, Andrew R Gennery, Su Han Lum, Stephen Owens","doi":"10.1007/s10875-024-01850-2","DOIUrl":"https://doi.org/10.1007/s10875-024-01850-2","url":null,"abstract":"<p><p>Receptor Interacting Serine/Threonine Kinase 1 (RIPK1) is widely expressed and integral to inflammatory and cell death responses. Autosomal recessive RIPK1-deficiency, due to biallelic loss of function mutations in RIPK1, is a rare inborn error of immunity (IEI) resulting in uncontrolled necroptosis, apoptosis and inflammation. Although hematopoietic stem cell transplantation (HSCT) has been suggested as a potential curative therapy, the extent to which disease may be driven by extra-hematopoietic effects of RIPK1-deficiency, which are non-amenable to HSCT, is not clear. We present a multi-centre, international review of an additional 5 RIPK1-deficient children who underwent HSCT. All patients presented with very early onset inflammatory bowel disease, 2 also suffered from inflammatory arthritis. Median age at transplant was 3 years (range 1-5 years); 1 received matched sibling marrow, 1 matched unrelated peripheral blood stem cells (PBSC), 2 TCRαβ/CD19-depleted PBSC from maternal-haploidentical donors, and 1 had TCRαβ/CD19-depleted PBSC from a mismatched unrelated donor. All received reduced-toxicity conditioning, based on treosulfan (n = 4) or busulfan (n = 1); 1 patient underwent a successful second transplant following autologous reconstitution. Four of five patients (80%) survived; 1 child died due to multi-drug resistant pseudomonas infection and multi-organ failure. With a median duration of 14 months follow-up, 2 survivors were disease-free, and 2 had substantially improving enteropathy. These findings demonstrated that HSCT is a potential curative therapy for RIPK1-deficiency.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"65"},"PeriodicalIF":7.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949810","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":"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/s10875-024-01854-y","DOIUrl":"10.1007/s10875-024-01854-y","url":null,"abstract":"<p><p>Allogeneic haematopoietic stem cell transplantation (alloHSCT) is safe and effective for adolescents and adults with inborn errors of immunity (IEI) with severe disease manifestations of their disease. The haematopoietic cell transplantation comorbidity index (HCT-CI) score predicts transplant survival in non-malignant diseases, including IEIs. We hypothesised that immune dysregulation pre-transplant may also influence transplant outcomes. We calculated the pre-transplant immune dysregulation and disease activity score (IDDA v2.1) for 82 adolescent and adult IEI patients (aged ≥ 13 years). Three-year overall survival (OS) for the whole cohort was 90% (n = 82) with a median follow up of 44.7 months (range 8.4 to 225.8). Events were defined as acute graft-versus-host disease (GvHD) grades II or above, chronic GvHD of any grade, graft failure, or death from any cause. Three-year event free survival (EFS) for the whole cohort was 72%. In multivariable analysis the IDDA v2.1 score pre-transplant and HCT-CI score significantly impacted OS (hazard ratio 1.08, p = 0.028) and EFS (hazard ratio 1.04, p = 0.0005). Importantly, 35% of this cohort had a high IDDA v2.1 score (≥ 15) and low HCT-CI score (< 3) suggesting that the risks of alloHSCT may be underestimated in a proportion of patients with IEI if the HCT-CI score is used alone. These findings support the potential for improved outcomes following successful modulation of immune dysregulation pre-transplant. The IDDA v2.1 score has utility as an objective measurement of pre-transplant immune dysregulation providing additional information reagrding the risks and potential complications of alloHSCT in an individual IEI patient.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"64"},"PeriodicalIF":7.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931899","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 Inherited N-terminus TAP1 Variants and Severe Clinical Manifestations- Are Genotype-Phenotype Correlations Emerging?","authors":"Dharmagat Bhattarai, Aaqib Zaffar Banday, Sheetal Sharda, Pratap Kumar Patra, Jolan E Walter, Kathleen E Sullivan","doi":"10.1007/s10875-024-01856-w","DOIUrl":"10.1007/s10875-024-01856-w","url":null,"abstract":"<p><p>Major histocompatibility complex class I deficiency results from deleterious biallelic variants in TAP1, TAP2, TAPBP, and B2M genes. Only a few patients with variant-curated TAP1 deficiency (TAP1D) have been reported in the literature and the clinical phenotype has been variable with an emphasis on autoimmune and inflammatory complications. We report TAP1D in a Nepalese girl with a severe clinical phenotype with serious viral infections at a very young age. A novel frameshift termination variant near the protein's amino (N-) terminal was found. Variants in exon 1 of the TAP1 gene (as in our case) have not been reported previously. We also perform a brief review of TAP1D that hints at potential genotype-phenotype correlations. However, these findings need to be interpreted with due prudence given the small number of patients with TAP1D reported thus far.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"63"},"PeriodicalIF":7.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921870","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":"Baricitinib-Induced Remission of Alopecia Universalis in a Child with NFKB2-Associated Immune Dysregulation.","authors":"C Blokhuis, T R Leahy, A D Irvine, F Browne, A M Flinn","doi":"10.1007/s10875-024-01852-0","DOIUrl":"https://doi.org/10.1007/s10875-024-01852-0","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"62"},"PeriodicalIF":7.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921859","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}