Journal of Clinical Immunology最新文献

{"title":"Evaluation of Frequency of CMV Replication and Disease Complications Reveals New Cellular Defects and a Time Dependent Pattern in CVID Patients.","authors":"Luca Marri, Paola Contini, Federico Ivaldi, Chiara Schiavi, Ottavia Magnani, Chiara Vassallo, Andrea Guastalla, Noemi Traversone, Claudia Angelini, Genny Del Zotto, Andrea De Maria, Raffaele De Palma","doi":"10.1007/s10875-024-01744-3","DOIUrl":"10.1007/s10875-024-01744-3","url":null,"abstract":"<p><strong>Purpose: </strong>Common Variable Immunodeficiency (CVID) is characterized by hypogammaglobulinemia and failure of specific antibody production due to B-cell defects. However, studies have documented various T-cell abnormalities, potentially linked to viral complications. The frequency of Cytomegalovirus (CMV) replication in CVID cohorts is poorly studied. To address this gap in knowledge, we set up an observational study with the objectives of identifying CVID patients with active viraemia (CMV, Epstein-Barr virus (EBV)), evaluating potential correlations with immunophenotypic characteristics, clinical outcome, and the dynamic progression of clinical phenotypes over time.</p><p><strong>Methods: </strong>31 CVID patients were retrospectively analysed according to viraemia, clinical and immunologic characteristics. 21 patients with non CVID humoral immunodeficiency were also evaluated as control.</p><p><strong>Results: </strong>Active viral replication of CMV and/or EBV was observed in 25% of all patients. CMV replication was detected only in CVID patients (16%). CVID patients with active viral replication showed reduced HLA-DR⁺ NK counts when compared with CMV-DNA negative CVID patients. Viraemic patients had lower counts of LIN^-DNAM^bright and LIN^-CD16⁺ inflammatory lymphoid precursors which correlated with NK-cell subsets. Analysis of the dynamic progression of CVID clinical phenotypes over time, showed that the initial infectious phenotype progressed to complicated phenotypes with time. All CMV viraemic patients had complicated disease.</p><p><strong>Conclusion: </strong>Taken together, an impaired production of inflammatory precursors and NK activation is present in CVID patients with active viraemia. Since \"Complicated\" CVID occurs as a function of disease duration, there is need for an accurate evaluation of this aspect to improve classification and clinical management of CVID patients.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 6","pages":"142"},"PeriodicalIF":7.2,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11161436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283800","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":"Disseminated BCG Disease in a Child with a Novel PSMG2 Deletion.","authors":"Agustín Bernacchia, Ana Luz Garcia, Andrea Gomez Raccio, Daniela Di Giovanni","doi":"10.1007/s10875-024-01738-1","DOIUrl":"10.1007/s10875-024-01738-1","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 6","pages":"145"},"PeriodicalIF":7.2,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283798","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":"An Exploratory Approach of Clinically Useful Biomarkers of Cvid by Logistic Regression.","authors":"Teresa Guerra-Galán, María Palacios-Ortega, Adolfo Jiménez-Huete, Kissy Guevara-Hoyer, María Cruz Cárdenas, Ángela Villegas-Mendiola, María Dolores Mansilla-Ruíz, Nabil Subhi-Issa, Eduardo de la Fuente-Munoz, Pedro Mikel Requejo, Antonia Rodríguez de la Peña, María Guzmán-Fulgencio, Miguel Fernández-Arquero, Rebeca Pérez de Diego, Silvia Sánchez-Ramón","doi":"10.1007/s10875-024-01746-1","DOIUrl":"10.1007/s10875-024-01746-1","url":null,"abstract":"<p><p>Despite advancements in genetic and functional studies, the timely diagnosis of common variable immunodeficiency (CVID) remains a significant challenge. This exploratory study was designed to assess the diagnostic performance of a novel panel of biomarkers for CVID, incorporating the sum of κ+λ light chains, soluble B-cell maturation antigen (sBCMA) levels, switched memory B cells (smB) and the VISUAL score. Comparative analyses utilizing logistic regression were performed against established gold-standard tests, specifically antibody responses. Our research encompassed 88 subjects, comprising 27 CVID, 23 selective IgA deficiency (SIgAD), 20 secondary immunodeficiency (SID) patients and 18 healthy controls. We established the diagnostic accuracy of sBCMA and the sum κ+λ, achieving sensitivity (Se) and specificity (Spe) of 89% and 89%, and 90% and 99%, respectively. Importantly, sBCMA showed strong correlations with all evaluated biomarkers (sum κ+λ, smB cell and VISUAL), whereas the sum κ+λ was uniquely independent from smB cells or VISUAL, suggesting its additional diagnostic value. Through a multivariate tree decision model, specific antibody responses and the sum κ+λ emerged as independent, signature biomarkers for CVID, with the model showcasing an area under the curve (AUC) of 0.946, Se 0.85, and Spe 0.95. This tree-decision model promises to enhance diagnostic efficiency for CVID, underscoring the sum κ+λ as a superior CVID classifier and potential diagnostic criterion within the panel.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 6","pages":"143"},"PeriodicalIF":7.2,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11161432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283797","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":"Implementation of a Reference Center for Inborn Errors of Immunity in Latin America.","authors":"Ana Carolina da Matta Ain, Lucila Akune Barreiros, Carolina Sanchez Aranda, Antonio Condino Neto","doi":"10.1007/s10875-024-01743-4","DOIUrl":"10.1007/s10875-024-01743-4","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 6","pages":"141"},"PeriodicalIF":7.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237117","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":"Neurological Diseases and Prevalence of Antineuronal Antibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1 - A National Cohort Study.","authors":"Sini M Laakso, Aino Häkkinen, Outi Mäkitie, Saila Laakso","doi":"10.1007/s10875-024-01748-z","DOIUrl":"10.1007/s10875-024-01748-z","url":null,"abstract":"<p><p>Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic disease caused by mutations in the autoimmune regulator gene. Although the disease-associated autoantibodies mostly target endocrine organs, autoantibodies from patients with APS-1 bind also to rat brain structures. The patients often have GAD65-antibodies, that can cause autoimmune encephalitis. However, neurological manifestations of APS-1 have not been systematically explored. We conducted a retrospective chart review on 44 Finnish patients with APS-1 (median age 38 years, 61% females) and collected all their neurological diagnoses. To assess the prevalence of serum antineuronal antibodies in APS-1, serum samples of 24 patients (median age 36 years, 63% females) were analyzed using a fixed cell-based assay. Of the 44 APS-1 patients, 10 (23%) had also received a diagnosis of a neurological disease. Of these neurological comorbidities, migraine (n = 7; 16%), central nervous system infections (n = 3; 7%), and epilepsy (n = 2; 5%) were the most prevalent. Other diagnoses recorded for single patients were axonal sensorimotor polyneuropathy, essential tremor, idiopathic intracranial hypertension, ischemic stroke, and trigeminal neuralgia. Serum antineuronal antibodies were detected in 42% of patients tested (10/24, 50% females, median age 42 years), GAD65 antibodies being the most common finding. Antibodies against glycine and aquaporin 4 were found in low titers. In four patients, relatively high titers of GAD65 antibodies without coexisting type 1 diabetes were found, but none presented with GAD65-encephalitis. Our study suggests an association between APS-1 and neurological disorders, the mechanisms of which are to be further investigated.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 6","pages":"140"},"PeriodicalIF":7.2,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11147840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141198894","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":"Unconventional T Cells Influence Clinical Outcome After Allogeneic Hematopoietic Cell Transplantation.","authors":"Lama Siblany, Nicolas Stocker, Laure Ricard, Eolia Brissot, Rémy Duléry, Anne Banet, Simona Sestili, Ramdane Belhocine, Zoé Van de Wyngaert, Agnès Bonnin, Antoine Capes, Tounes Ledraa, Pauline Beurier, Karen Fadel, Mohamad Mohty, Béatrice Gaugler, Florent Malard","doi":"10.1007/s10875-024-01741-6","DOIUrl":"10.1007/s10875-024-01741-6","url":null,"abstract":"<p><p>We evaluated the impact of early recovery of mucosal-associated invariant T cells (MAIT) and gamma-delta (γδ) T cells, especially Vδ2⁺ T cells, on the clinical outcomes of 76 patients who underwent allogeneic hematopoietic cell transplantation (allo-HCT). MAIT cells were identified at day 20-30 post-transplant using flow cytometry and defined as CD3⁺ TCRVα7.2⁺CD161⁺. Two subsets of Vδ2⁺ T cells were analyzed according to the expression of CD26. The cytotoxicity profile of MAIT and Vδ2⁺ T cells was analyzed according to the intracellular expression of perforin and granzyme B, and intracellular IFN-γ was evaluated after in vitro activation. CD26⁺Vδ2⁺ T cells displayed higher intracellular levels of IFN-γ, whereas CD26^- Vδ2⁺ T were found to be more cytotoxic. Moreover, MAIT cell frequency was correlated with the frequency of Vδ2⁺ T cells with a better correlation observed with Vδ2⁺CD26⁺ than with the Vδ2⁺CD26^- T cell subset. By using the composite endpoint graft-versus-host disease (GvHD)-free, relapse-free survival (GRFS) as the primary endpoint, we found that patients with a higher MAIT cell frequency at day 20-30 after allo-HCT had a significantly increased GRFS and a better overall survival (OS) and disease-free survival (DFS). Moreover, patients with a low CD69 expression by MAIT cells had an increased cumulative incidence of grade 2-4 acute GvHD (aGvHD). These results suggest that MAIT cell reconstitution may provide mitigating effects early after allo-HCT depending on their activation markers and functional status. Patients with a high frequency of Vδ2⁺CD26⁺ T cells had a significantly higher GRFS, OS and DFS, but there was no impact on cumulative incidence of grade 2-4 aGVHD, non-relapse mortality and relapse. These results revealed that the impact of Vδ2⁺ T cells on the success of allo-HCT may vary according to the frequency of the CD26⁺ subset.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 6","pages":"139"},"PeriodicalIF":7.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186681","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":"Cancer Prevalence in Children with Inborn Errors of Immunity: Report from a Single Institution.","authors":"María Raquel Mitchell, Luciano Urdinez, Andrea R Bernasconi, Silvia Danielian, María Martha Katsikas, Elisa O Sajaroff, Georgina Roffé, Nélida M Villa, Laura Galluzzo, Marianela Sanz, Alejandro M Palma, Carolina Bouso, Emma Prieto, Verónica Goris, Judith Yancoski, Sergio D Rosenzweig, Matías Oleastro, Adriana Rosé, Walter Cacciavillano, Guido Felizzia, Myriam Guitter, Cristian Sánchez La Rosa, Mailén Ríos, Pedro Zubizarreta, María Sara Felice, Jorge G Rossi","doi":"10.1007/s10875-024-01736-3","DOIUrl":"10.1007/s10875-024-01736-3","url":null,"abstract":"<p><strong>Background: </strong>Inborn Errors of Immunity (IEI) comprise several genetic anomalies that affect different components of the innate and adaptive responses, predisposing to infectious diseases, autoimmunity and malignancy. Different studies, mostly in adults, have reported a higher prevalence of cancer in IEI patients. However, in part due to the rarity of most of these IEI subtypes (classified in ten categories by the Primary Immunodeficiency Committee of the International Union of Immunological Societies), it is difficult to assess the risk in a large number of patients, especially during childhood.</p><p><strong>Objective: </strong>To document the cancer prevalence in a pediatric cohort from a single referral institution, assessing their risk, together with the type of neoplasia within each IEI subgroup.</p><p><strong>Method: </strong>An extensive review of clinical records from 1989 to 2022 of IEI patients who at some point developed cancer before the age of sixteen.</p><p><strong>Results: </strong>Of a total of 1642 patients with IEI diagnosis, 34 developed cancer before 16 years of age, showing a prevalence (2.1%) significantly higher than that of the general age matched population (0.22). Hematologic neoplasms (mostly lymphomas) were the most frequent malignancies.</p><p><strong>Conclusion: </strong>This study represents one of the few reports focused exclusively in pediatric IEI cases, describing not only the increased risk of developing malignancy compared with the age matched general population (a fact that must be taken into account by immunologists during follow-up) but also the association of the different neoplasms with particular IEI subtypes, thus disclosing the possible mechanisms involved.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 6","pages":"138"},"PeriodicalIF":7.2,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158337","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":"Fluoxetine Successfully Treats Intracranial Enterovirus E18 Infection in a Patient with CD79a Deficiency Arising from Segmental Uniparental Disomy of Chromosome 19.","authors":"Lang Yu, Yishi Zhang, Wenhui Li, Jinxiao Mao, Yulin Li, Haoru Wang, Chenlin Li, Lu Yang, Wenli He, Yanjun Jia, Wenjing Tang, Lina Zhou, Zhiyong Zhang, Yuntao Jia, Xuemei Tang, Xiaodong Zhao, Yunfei An","doi":"10.1007/s10875-024-01740-7","DOIUrl":"10.1007/s10875-024-01740-7","url":null,"abstract":"<p><p>The pre BCR complex plays a crucial role in B cell production, and its successful expression marks the B cell differentiation from the pro-B to pre-B. The CD79a and CD79b mutations, encoding Igα and Igβ respectively, have been identified as the cause of autosomal recessive agammaglobulinemia (ARA). Here, we present a case of a patient with a homozygous CD79a mutation, exhibiting recurrent respiratory infections, diarrhea, growth and development delay, unique facial abnormalities and microcephaly, as well as neurological symptoms including tethered spinal cord, sacral canal cyst, and chronic enteroviral E18 meningitis. Complete blockade of the early B cell development in the bone marrow of the patient results in the absence of peripheral circulating mature B cells. Whole exome sequencing revealed a Loss of Heterozygosity (LOH) of approximately 19.20Mb containing CD79a on chromosome 19 in the patient. This is the first case of a homozygous CD79a mutation caused by segmental uniparental diploid (UPD). Another key outcome of this study is the effective management of long-term chronic enteroviral meningitis using a combination of intravenous immunoglobulin (IVIG) and fluoxetine. This approach offers compelling evidence of fluoxetine's utility in treating enteroviral meningitis, particularly in immunocompromised patients.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 6","pages":"137"},"PeriodicalIF":7.2,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158338","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":"NF-κB Activation and X-Inactivation in Females with Incontinentia Pigmenti and Recurrent Infections.","authors":"Laura Krogh Herlin, Signe Bech Sørensen, Jesper Aagaard Graakjaer, Sisse Andersen, Sigrun Alba Johannesdottir Schmidt, Mette Sommerlund, Trine H Mogensen","doi":"10.1007/s10875-024-01737-2","DOIUrl":"10.1007/s10875-024-01737-2","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 6","pages":"136"},"PeriodicalIF":7.2,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097113","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":"Correction to: Monozygotic Twins with MAGT1 Deficiency and Epstein-Barr virus-positive Classic Hodgkin Lymphoma Receiving anti-CD30 CAR T-cell Immunotherapy: A case Report.","authors":"Jiachen Wang, Mi Zhou, Jianfeng Zhou, Min Xiao, Liang Huang","doi":"10.1007/s10875-024-01723-8","DOIUrl":"10.1007/s10875-024-01723-8","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 6","pages":"135"},"PeriodicalIF":7.2,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097111","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}