PMID- 33421202 OWN - NLM STAT- MEDLINE DCOM- 20210823 LR - 20220531 IS - 1399-3038 (Electronic) IS - 0905-6157 (Print) IS - 0905-6157 (Linking) VI - 32 IP - 4 DP - 2021 May TI - Association between human leukocyte antigens (HLAs) and human neutrophil antigens (HNAs) and autoimmune neutropenia of infancy in Danish patients. PG - 756-761 LID - 10.1111/pai.13450 [doi] AB - 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 (FcgammaIIIb). 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-FcgammaIIIb-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. CI - (c) 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd. FAU - Nielsen, Kaspar Rene AU - Nielsen KR AUID- ORCID: 0000-0003-4406-9643 AD - Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark. FAU - Bojsen, Signe Rolskov AU - Bojsen SR AD - Department of Clinical Genetics, Sygehus Lillebaelt Vejle Hospital, Vejle, Denmark. FAU - Masmas, Tania Nicole AU - Masmas TN AD - Pediatric Hematopoietic Stem Cell Transplantation and Immunodeficiency, The Child and Adolescent Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. FAU - Fjordside, Anne-Louise AU - Fjordside AL AD - Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark. FAU - Baech, John AU - Baech J AD - Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark. FAU - Haunstrup, Thure Mors AU - Haunstrup TM AD - Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark. FAU - Steffensen, Rudi AU - Steffensen R AD - Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark. LA - eng PT - Journal Article DEP - 20210209 PL - England TA - Pediatr Allergy Immunol JT - Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology JID - 9106718 RN - 0 (HLA Antigens) SB - IM MH - Autoimmunity MH - Denmark MH - Genotype MH - HLA Antigens MH - Humans MH - Infant MH - *Neutropenia MH - *Neutrophils PMC - PMC8248029 OTO - NOTNLM OT - HLA OT - HNA OT - autoimmune OT - genotype OT - neutropenia COIS- On behalf of all authors, I hereby declare no conflicts of interest. EDAT- 2021/01/10 06:00 MHDA- 2021/08/24 06:00 PMCR- 2021/07/01 CRDT- 2021/01/09 17:10 PHST- 2020/12/09 00:00 [revised] PHST- 2020/08/04 00:00 [received] PHST- 2020/12/16 00:00 [accepted] PHST- 2021/01/10 06:00 [pubmed] PHST- 2021/08/24 06:00 [medline] PHST- 2021/01/09 17:10 [entrez] PHST- 2021/07/01 00:00 [pmc-release] AID - PAI13450 [pii] AID - 10.1111/pai.13450 [doi] PST - ppublish SO - Pediatr Allergy Immunol. 2021 May;32(4):756-761. doi: 10.1111/pai.13450. Epub 2021 Feb 9.