Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells
نویسندگان
چکیده
Common variable immunodeficiency disorder (CVID) is the most common symptomatic primary immunodeficiency in adults, characterized by B-cell abnormalities and inadequate antibody response. CVID patients have considerable autoimmune comorbidity and we therefore hypothesized that genetic susceptibility to CVID may overlap with autoimmune disorders. Here, in the largest genetic study performed in CVID to date, we compare 778 CVID cases with 10,999 controls across 123,127 single-nucleotide polymorphisms (SNPs) on the Immunochip. We identify the first non-HLA genome-wide significant risk locus at CLEC16A (rs17806056, P=2.0 × 10(-9)) and confirm the previously reported human leukocyte antigen (HLA) associations on chromosome 6p21 (rs1049225, P=4.8 × 10(-16)). Clec16a knockdown (KD) mice showed reduced number of B cells and elevated IgM levels compared with controls, suggesting that CLEC16A may be involved in immune regulatory pathways of relevance to CVID. In conclusion, the CLEC16A associations in CVID represent the first robust evidence of non-HLA associations in this immunodeficiency condition.
منابع مشابه
The Significance of B-cell Subsets in Patients with Unclassified Hypogammaglobulinemia and Association with Intravenous Immunoglobulin Replacement Requirement
Background: Patients with unclassified hypogammaglobulinemia (UCH) constitute a diagnostic and therapeutic dilemma, because information concerning the clinical and immunological characteristics of these patients is insufficient. Objective: To evaluate B-cell subsets in cases with UCH and common variable immunodeficiency (CVID) and their association with treatment requirement in UCH patients. Me...
متن کاملA 20-YEAR SURVEY OF INFECTIOUS COMPLICATIONS IN 64 PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY
Common variable immunodeficiency (CV ID) is a heterogeneous primary immunodeficiency disorder, characterized by hypogammaglobulinemia and increased susceptibility to recurrent bacterial infections. To determine the spectrum of infectious complications in patients with common variable immunodeficiency (CV ID), we reviewed the hospital records of 64 CVID patients, who were diagnosed in Child...
متن کاملPrimary Antibody Deficiencies at Queen Rania Children Hospital in Jordan: Single Center Experience
Background: Primary antibody deficiency, the most common primary immunodeficiency disorder, represents a heterogeneous spectrum of conditions caused by a defect in any critical stage of B cell development and is characterized by impaired production of normal amounts of antigen-specific antibodies. Objective: This retrospective study aimed at description and analysis of demographic, clinical, im...
متن کاملThe Role of Tumor Protein 53 Mutations in Common Human Cancers and Targeting the Murine Double Minute 2–P53 Interaction for Cancer Therapy
The gene TP53 (also known as protein 53 or tumor protein 53), encoding transcription factor P53, is mutated or deleted in half of human cancers, demonstrating the crucial role of P53 in tumor suppression. There are reports of nearly 250 independent germ line TP53 mutations in over 100 publications. The P53 protein has the structure of a transcription factor and, is made up of several domains. T...
متن کاملA CASE REPORT OF COMMON VARIABLE IMMUNODEFICIENCY(CV ID) WITH LEUKOCYTES ADHESION DISORDERS (LADS)
A three year old boy with delayed separation of the umbilical cord, recurrent pyogenic infections and common variable immundeficiency is presented. The immunoglobulin measurement was severely abnormal. To the best of our knowledge, the existance of leukocyte adhesion disorder together with common variable immunodeficiency (CYID) in a patient has not been reported prior to this study.
متن کامل