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Genetic variations in low-to-medium-affinity Fcγ receptors and autoimmune neutropenia in early childhood in a Danish cohort.
Kløve-Mogensen, Kirstine; Steffensen, Rudi; Masmas, Tania Nicole; Glenthøj, Andreas; Jensen, Christina Friis; Haunstrup, Thure Mors; Ratcliffe, Paul; Höglund, Petter; Hasle, Henrik; Nielsen, Kaspar René.
Afiliação
  • Kløve-Mogensen K; Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
  • Steffensen R; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
  • Masmas TN; Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
  • Glenthøj A; Pediatric Hematopoietic Stem Cell Transplantation and Immunodeficiency, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Jensen CF; Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Haunstrup TM; Department of Pediatrics and Adolescent Medicine, Aalborg University Hospital, Aalborg, Denmark.
  • Ratcliffe P; Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
  • Höglund P; Department of medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
  • Hasle H; Department of medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
  • Nielsen KR; Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
Int J Immunogenet ; 50(2): 65-74, 2023 Apr.
Article em En | MEDLINE | ID: mdl-36754570
ABSTRACT
Autoimmune neutropenia (AIN) in early childhood is caused by autoantibodies directed against antigens on the neutrophil membrane and is a frequent cause of neutropenia in children. Association of AIN with Fcγ receptor (FCGR) 3B variants is well described. In this study, we investigate genetic variations in the FCGR locus and copy number variation of FCGR3B. A total of 130 antibody-positive AIN patients, 64 with specific anti-HNA-1a antibodies and 66 with broad-reacting anti-FcγRIIIb antibodies, were genotyped with a multiplex ligation probe assay and compared with healthy controls. Positive findings were confirmed with real-time q-PCR. We determined copy numbers of the FCGR2 and FCGR3 genes and the following SNPs FCGR2A Q62W (rs201218628), FCGR2A H166R (rs1801274), FCGR2B I232T (rs1050501), FCGR3A V176F (rs396991), haplotypes for FCGR2B/C promoters (rs3219018/rs780467580), FCGR2C STOP/ORF and HNA-1 genotypes in FCGR3B (rs447536, rs448740, rs52820103, rs428888 and rs2290834). Generally, associations were antibody specific, with all associations being representative of the anti-HNA-1a-positive group, while the only association found in the anti-FcγRIIIb group was with the HNA-1 genotype. An increased risk of AIN was observed for patients with one copy of FCGR3B; the HNA genotypes HNA-1a, HNA-1aa or HNA-1aac; the FCGR2A 166H and FCGR2B 232I variations; and no copies of FCGR2B 2B.4. A decreased risk was observed for HNA genotype HNA-1bb; FCGR2A 166R; FCGR2B 232T; and one copy of FCGR2B promoter 2B.4. We conclude that in our Danish cohort, there was a strong association between variation in the FCGR locus and AIN. The findings of different genetic associations between autoantibody groups could indicate the presence of two different disease entities and disease heterogeneity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Neutropenia Tipo de estudo: Risk_factors_studies Limite: Child / Child, preschool / Humans País/Região como assunto: Europa Idioma: En Revista: Int J Immunogenet Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Neutropenia Tipo de estudo: Risk_factors_studies Limite: Child / Child, preschool / Humans País/Região como assunto: Europa Idioma: En Revista: Int J Immunogenet Ano de publicação: 2023 Tipo de documento: Article