loading page

Association between human leukocyte antigens (HLAs) and human neutrophil antigens (HNAs) and autoimmune neutropenia of infancy in Danish patients
  • +4
  • Kaspar Nielsen,
  • Signe Bojsen,
  • Tania Masmas,
  • Anne-Louise Fjordside,
  • John Baech,
  • Thure Haunstrup,
  • Rudi Steffensen
Kaspar Nielsen
Aalborg University Hospital

Corresponding Author:[email protected]

Author Profile
Signe Bojsen
Sygehus Lillebaelt Vejle Hospital, Denmark
Author Profile
Tania Masmas
Copenhagen University Hospital, Copenhagen, Denmark.
Author Profile
Anne-Louise Fjordside
Aalborg University Hospital
Author Profile
John Baech
Aalborg University Hospital
Author Profile
Thure Haunstrup
Aalborg University Hospital
Author Profile
Rudi Steffensen
Aalborg University Hospital
Author Profile

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.
02 Aug 2020Submitted to Pediatric Allergy and Immunology
11 Aug 2020Reviewer(s) Assigned
02 Sep 2020Review(s) Completed, Editorial Evaluation Pending
03 Sep 2020Editorial Decision: Revise Major
09 Nov 20201st Revision Received
10 Nov 2020Review(s) Completed, Editorial Evaluation Pending
11 Nov 2020Reviewer(s) Assigned
01 Dec 2020Editorial Decision: Revise Minor
08 Dec 20202nd Revision Received
10 Dec 2020Review(s) Completed, Editorial Evaluation Pending
16 Dec 2020Editorial Decision: Accept
09 Jan 2021Published in Pediatric Allergy and Immunology. 10.1111/pai.13450