Journal of Clinical Immunology最新文献

{"title":"Successful Allogeneic Hematopoietic Cell Transplantation for Patients with IL10RA Deficiency in Japan","authors":"Dan Tomomasa, Tasuku Suzuki, Ichiro Takeuchi, Kimitoshi Goto, Shin-Ichiro Hagiwara, Dai Keino, Satoshi Saida, Takashi Ishige, Takahiro Kudo, Katsuhide Eguchi, Masataka Ishimura, Yusuke Matsuda, Taizo Wada, Yoshiya Ito, Motohiro Kato, Yoji Sasahara, Tomohiro Morio, Katsuhiro Arai, Holm H Uhlig, Hirokazu Kanegane","doi":"10.1007/s10875-024-01795-6","DOIUrl":"https://doi.org/10.1007/s10875-024-01795-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>IL10RA (IL10 receptor subunit alpha) deficiency is an autosomal recessive disease that causes inflammatory bowel disease during early infancy. Its clinical course is often fatal and the only curative treatment is allogeneic hematopoietic cell transplantation (HCT). In Japan, only case reports are available, and there are no comprehensive reports of treatment outcomes.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We retrospectively analyzed patients with IL10RA deficiency in Japan.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Two newly identified and five previously reported patients were included in this study. Five patients underwent HCT; one untransplanted patient survived to age 14, and one died of influenza encephalopathy before transplantation. All five HCT recipients underwent HCT at the age before 2 years. They all were conditioned with fludarabine/busulfan- or fludarabine /melphalan-based regimens. The donor source was human leukocyte antigen haploidentical donor bone marrow (BM) for two patients and unrelated umbilical cord blood (CB) for two patients. One patient experienced graft failure with unrelated CB and required a second transplant with unrelated BM. All patients who underwent HCT survived and demonstrated an improved performance status.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In cases of IL10RA deficiency, the need for transplantation should be promptly assessed, and early transplantation should be considered. (190/250)</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212571","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":"Non-Skewed X-inactivation Results in NF-κB Essential Modulator (NEMO) Δ-exon 5-autoinflammatory Syndrome (NEMO-NDAS) in a Female with Incontinentia Pigmenti","authors":"Jessica Eigemann, Ales Janda, Catharina Schuetz, Min Ae Lee-Kirsch, Ansgar Schulz, Manfred Hoenig, Ingrid Furlan, Eva-Maria Jacobsen, Julia Zinngrebe, Sarah Peters, Cosima Drewes, Reiner Siebert, Eva-Maria Rump, Marita Führer, Myriam Lorenz, Ulrich Pannicke, Uwe Kölsch, Klaus-Michael Debatin, Horst von Bernuth, Klaus Schwarz, Kerstin Felgentreff","doi":"10.1007/s10875-024-01799-2","DOIUrl":"https://doi.org/10.1007/s10875-024-01799-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Genetic hypomorphic defects in X chromosomal <i>IKBKG</i> coding for the NF-κB essential modulator (NEMO) lead to ectodermal dysplasia and immunodeficiency in males and the skin disorder incontinentia pigmenti (IP) in females, respectively. NF-κB essential modulator (NEMO) Δ-exon 5-autoinflammatory syndrome (NEMO-NDAS) is a systemic autoinflammatory disease caused by alternative splicing and increased proportion of NEMO-Δex5. We investigated a female carrier presenting with IP and NEMO-NDAS due to non-skewed X-inactivation.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p><i>IKBKG</i> transcripts were quantified in peripheral blood mononuclear cells isolated from the patient, her mother, and healthy controls using RT-PCR and nanopore sequencing. Corresponding proteins were analyzed by western blotting and flow cytometry. Besides toll-like receptor (TLR) and tumor necrosis factor (TNF) signaling, the interferon signature, cytokine production and X-inactivation status were investigated.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>IP and autoinflammation with recurrent fever, oral ulcers, hepatitis, and neutropenia, but no immunodeficiency was observed in a female patient. Besides moderately reduced NEMO signaling function, type I interferonopathy, and elevated IL-18 and CXCL10 were found. She and her mother both carried the heterozygous variant c.613 C &gt; T p.(Gln205*) in exon 5 of <i>IKBKG</i> previously reported in NEMO-deficient patients. However, X-inactivation was skewed in the mother, but not in the patient. Alternative splicing led to increased ratios of NEMO-Dex5 over full-length protein in peripheral blood cell subsets causing autoinflammation. Clinical symptoms partially resolved under treatment with TNF inhibitors.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Non-skewed X-inactivation can lead to NEMO-NDAS in females with IP carrying hypomorphic <i>IKBKG</i> variants due to alternative splicing and increased proportions of NEMO-∆ex5.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212567","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":"Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) Associated with GlyR Antibody in an APECED Patient.","authors":"Sebastian Ochoa,Patrick Waters,Eléonore Vieillard,Ariane Soldatos,M Isabel Leite,Michail S Lionakis","doi":"10.1007/s10875-024-01802-w","DOIUrl":"https://doi.org/10.1007/s10875-024-01802-w","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212574","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":"Successful Haematopoietic Stem Cell Transplantation for LRBA Deficiency with Fludarabine, Treosulfan, and Thiotepa-Based Conditioning","authors":"Bella Shadur, Adeeb NasserEddin, Irina Zaidman, Yael Dinur Schejter, Ehud Even-Or, Yackov Berkun, Isabelle Meyts, Hatem Hmedat, Ashraf Sulaiman, Stuart G. Tangye, Polina Stepensky","doi":"10.1007/s10875-024-01770-1","DOIUrl":"https://doi.org/10.1007/s10875-024-01770-1","url":null,"abstract":"<p>LRBA deficiency is an inborn error of immunity defined by autoimmunity, lymphoproliferation, recurrent infections, cytopenia, and inflammatory bowel disease. Despite recent advances in managing this disease with targeted biologic therapy, haematopoietic stem cell transplant (HSCT) remains the only cure. However, great variability exists between protocols used to transplant patients with LRBA deficiency. We describe a cohort of seven patients with LRBA deficiency who underwent HSCT using a myeloablative, reduced toxicity regime of fludarabine, treosulfan, and thiotepa at two transplantation centres from 2016 to 2019. Data were collected both retrospectively and prospectively, measuring time to engraftment, infectious complications, incidence of graft versus host disease, and post-transplantation chimerism. Six of seven patients survived transplantation, and four of six surviving patients achieving treatment-free survival. We thus recommend that HSCT with fludarabine, treosulfan, and thiotepa-based conditioning be considered in patients with LRBA deficiency.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212568","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":"Successful Long-Term Enzyme Replacement Therapy in a Patient with Delayed-Onset ADA Deficiency","authors":"Vasil Toskov, Pawan Bali, Michael S. Hershfield, Stephan Ehl, Carsten Speckmann","doi":"10.1007/s10875-024-01794-7","DOIUrl":"https://doi.org/10.1007/s10875-024-01794-7","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212573","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":"HSCT in a Patient with Cernunnos/XLF Deficiency and Omenn Syndrome","authors":"Marwa Chbihi, Léa Nabhan, Antoine Pinton, Philippe Drabent, Jean-Pierre de Villartay, Bénédicte Neven","doi":"10.1007/s10875-024-01765-y","DOIUrl":"https://doi.org/10.1007/s10875-024-01765-y","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212570","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":"Abnormal Immune Profile in Individuals with Kabuki Syndrome","authors":"Margot Comel, Norma Saad, Debapratim Sil, Florence Apparailly, Marjolaine Willems, Farida Djouad, Jean-Christophe Andrau, Claire Lozano, David Genevieve","doi":"10.1007/s10875-024-01796-5","DOIUrl":"https://doi.org/10.1007/s10875-024-01796-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>To analyze the lymphocyte subsets in individuals with Kabuki syndrome for better characterizing the immunological phenotype of this rare congenital disorder.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We characterized the immunological profile including B-, T- and natural killer-cell subsets in a series (<i>N</i> = 18) of individuals with Kabuki syndrome.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>All 18 individuals underwent genetic analysis: 15 had a variant in <i>KMT2D</i> and 3 a variant in <i>KDM6A</i>. Eleven of the 18 individuals (61%) had recurrent infections and 9 (50%) respiratory infections. Three (17%) had autoimmune diseases. On immunological analysis, 6 (33%) had CD4 T-cell lymphopenia, which was preferentially associated with the <i>KMT2D</i> truncating variant (5/9 individuals). Eight of 18 individuals (44%) had a humoral deficiency and eight (44%) had B lymphopenia. We found abnormal distributions of T-cell subsets, especially a frequent decrease in recent thymic emigrant CD4 + naive T-cell count in 13/16 individuals (81%).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The immunological features of Kabuki syndrome showed variable immune disorders with CD4 + T-cell deficiency in one third of cases, which had not been previously reported. In particular, we found a reduction in recent thymic emigrant naïve CD4 + T-cell count in 13 of 16 individuals, representing a novel finding that had not previously been reported.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212572","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":"Hyperferritinemia Screening to Aid Identification and Differentiation of Patients with Hyperinflammatory Disorders","authors":"Hallie A. Carol, Adam S. Mayer, Michael S. Zhang, Vinh Dang, Jemy Varghese, Zachary Martinez, Corinne Schneider, Joy (Elizabeth) Baker, Paul Tsoukas, Edward M. Behrens, Randy Q. Cron, Caroline Diorio, Lauren A. Henderson, Grant Schulert, Pui Lee, Kate F. Kernan, Scott W. Canna","doi":"10.1007/s10875-024-01797-4","DOIUrl":"https://doi.org/10.1007/s10875-024-01797-4","url":null,"abstract":"<p>High ferritin is an important and sensitive biomarker for the various forms of hemophagocytic lymphohistiocytosis (HLH), a diverse and deadly group of cytokine storm syndromes. Early action to prevent immunopathology in HLH often includes empiric immunomodulation, which can complicate etiologic work-up and prevent collection of early/pre-treatment research samples. To address this, we instituted an alert system at UPMC Children’s Hospital where serum ferritin &gt; 1000 ng/mL triggered real-time chart review, assessment of whether the value reflected “inflammatory hyperferritnemia (IHF)”, and biobanking of remnant samples from consenting IHF patients. We extracted relevant clinical data; periodically measured serum total IL-18, IL-18 binding protein (IL-18BP), and CXCL9; retrospectively classified patients by etiology into infectious, rheumatic, or immune dysregulation; and subjected a subgroup of samples to a 96-analyte biomarker screen. 180 patients were identified, 30.5% of which had IHF. Maximum ferritin levels were significantly higher in patients with IHF than with either hemoglobinopathy or transplant, and highly elevated total IL-18 levels were distinctive to patients with Stills Disease and/or Macrophage Activation Syndrome (MAS). Multi-analyte analysis showed elevation in proteins associated with cytotoxic lymphocytes in all IHF samples when compared to healthy controls and depression of proteins such as ANGPT1 and VEGFR2 in samples from hyperferritinemic sepsis patients relative to non-sepsis controls. This real-time IFH screen proved feasible and efficient, validated prior observations about the specificity of IL-18, enabled early sample collection from a complex population, suggested a unique vascular biomarker signature in hyperferritinemic sepsis, and expanded our understanding of IHF heterogeneity.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142212569","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":"Severe Extrahematopoietic Manifestations in Complete STAT1 LOF after Successful Allogeneic HCT.","authors":"Friederike Frieß, Michael Flaig, Michael H Albert, Christoph Klein, Fabian Hauck","doi":"10.1007/s10875-024-01789-4","DOIUrl":"10.1007/s10875-024-01789-4","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125903","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":"Expanding the Clinical Phenotype with CD79A Mutation and Refractory Helicobacter Bilis Infection.","authors":"Archan Sil, Suprit Basu, Kanika Arora, Raju Khubchandani, Amit Rawat, Deepti Suri","doi":"10.1007/s10875-024-01792-9","DOIUrl":"10.1007/s10875-024-01792-9","url":null,"abstract":"<p><p>Autosomal recessive agammaglobulinemia is a severe primary antibody deficiency disorder typically presenting in infancy. We present a rare case of an 8-year-old boy with AR agammaglobulinemia due to a homozygous splice site variant (c.499-1G > A) in the CD79A gene. Despite monthly intravenous immunoglobulin replacement and prophylactic antibiotics, he developed refractory Helicobacter bilis leg ulcers. Helicobacter species are known for extracellular colonization and are challenging to culture, necessitating molecular diagnostics for identification. The patient required prolonged treatment with intravenous meropenem followed by oral metronidazole and doxycycline for resolution of the ulcers over two years. The patient also exhibited persistent asymptomatic thrombocytopenia, an atypical finding in CD79A mutation cases. This case underscores the importance of genetic diagnosis and targeted antimicrobial therapy in managing rare infections associated with primary immunodeficiencies like autosomal recessive agammaglobulinemia due to CD79A mutation.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107943","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}