Association between human leukocyte antigens (HLAs) and human neutrophil
antigens (HNAs) and autoimmune neutropenia of infancy in Danish patients
Abstract
Autoimmune neutropenia of infancy (AIN) is a relatively frequent cause
of neutropenia in children. The disease is caused by antibodies
recognizing membrane antigens of neutrophils, mostly located on
immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb receptor). In this
study, 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
anti-HNA-1a autoantibodies. Eighty AIN cases with a median age of 13.5
months were included in this study. Controls were healthy unrelated
Danish blood donors. Anti-HNA-1a autoantibodies were detected using a
flow cytometric granulocyte immunofluorescence test (Flow-GIFT).
Molecular determination of HNA genotypes was determined using real-time
polymerase chain reaction (q-PCR). High-resolution HLA-DR and HLA-DQB1
were determined by next-generation sequencing. 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. FCGR3B*01+,*02-,*03- was more common
(odds ratio, 6.70; p < 0.0001), and FCGR3B*01-,*02+,*03- was
less common (odds ratio, 0.30; p < 0.0001) 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 <
0.007). The HLA-DR*14 and HLA-DQB1*05:03 alleles were significantly more
common (odds ratio, 7.44; p < 0.0001 and odds ratio, 2.50; p
< 0.0001, respectively) in AIN patients. In conclusion the HLA
haplotype HLA-DR*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.