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Association between human leukocyte antigens (HLAs) and human neutrophil antigens (HNAs) and autoimmune neutropenia of infancy in Danish patients
Author(s) -
Nielsen Kaspar René,
Bojsen Signe Rolskov,
Masmas Tania Nicole,
Fjordside AnneLouise,
Baech John,
Haunstrup Thure Mors,
Steffensen Rudi
Publication year - 2021
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/pai.13450
Subject(s) - medicine , immunology , autoantibody , odds ratio , human leukocyte antigen , antibody , antigen , genotype , haplotype , neutropenia , biology , genetics , gene , toxicity
Background Autoimmune neutropenia of infancy (AIN) is a frequent cause of neutropenia in children. The disease is caused by antibodies against epitopes on the immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb). We investigated the possible association of human neutrophil antigens (HNA), human leukocyte antigen (HLA)‐DR, and HLA‐DQ alleles with AIN and the association of these genotypes with the presence of autoantibodies. Methods Eighty AIN cases with a median age of 13.5 months were included. Controls were healthy unrelated Danish blood donors. Anti‐HNA‐1a autoantibodies were detected using a flow cytometric granulocyte immunofluorescence test (Flow‐GIFT) with phenotyped donor cells for detection of antibody specificity. Molecular determination of HNA genotypes was determined using real‐time polymerase chain reaction (q‐PCR). High‐resolution HLA‐DRB1 and HLA‐DQB1 were determined by next‐generation sequencing. Results Antibodies against HNA‐1a were detected in 51% (n = 41) of AIN patients, and anti‐HNA‐1b was detected in 3% (n = 2) of cases. In 46% of cases, the antibodies were anti‐FcγIIIb‐reactive. FCGR3B*01+,*02‐,*03‐ was more common (odds ratio, 6.70; P < .0001), and FCGR3B*01‐,*02+,*03‐ was less common (odds ratio, 0.30; P < .0001) among AIN cases. HNA‐1a antibodies were significantly more frequent among AIN cases with the FCGR3B*01+,*02‐,*03‐ genotype (odds ratio, 3.86; P < .007). The HLA‐DRB1*14 ‐ HLA‐DQB1*05:03 haplotype was significantly more common (odds ratio, 7.44; P < .0001) in AIN patients. Conclusion The HLA haplotype HLA‐DRB1*14 ‐ DQB1*05:03 is associated with Danish AIN cases. Among Danish AIN patients, anti‐HNA‐1a is the most common autoantibody, and the antibody is more common in cases with the FCGR3B*01+,*02‐,*03‐ genotype.