Association between human leukocyte antigens (HLAs) and human neutrophil antigens (HNAs) and autoimmune neutropenia of infancy in Danish patients

Abstract

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Genetic variations in low‐to‐medium‐affinity Fcγ receptors and autoimmune neutropenia in early childhood in a Danish cohort

“…We observed an association with a lower number of copies of FCGR3B for the group of patients who were anti‐HNA‐1a positive (OR = 3.15 (1.23–8.06)), indicating similarities to other autoimmune diseases also associated with lower copy numbers. Consistent with our previously published data (Nielsen et al., 2021), the HNA‐1a genotype appears to be present in all anti‐HNA‐1a‐positive cases, and we can now extend this knowledge by also comparing the number of copies of HNA‐1a genotypes. Having only one copy of FCGR3B , which is an HNA‐1a genotype, does indeed induce the risk of getting AIN (OR = 6.49 (1.92–21.93)), but the association is clearly driven by the group of patients who are anti‐HNA‐1a positive (OR = 12.16 (3.45–42.8)), while there appears to be no association for the anti‐FcγRIIIb‐positive patients.…”

“…Audrain et al. (2011) reported similar findings in a French AIN cohort, and our group confirmed these findings and discovered that the presence of the HNA‐1a genotype appeared to be responsible for all anti‐HNA‐1a‐positive cases (Nielsen et al., 2021).…”

“…who were anti-HNA-1a positive)), indicating similarities to other autoimmune diseases also associated with lower copy numbers. Consistent with our previously published data(Nielsen et al, 2021), the HNA-1a genotype appears to be present in all anti-HNA-1a-positive cases, and we can now extend this knowledge by TA B L E 1 ****Significance level after Bonferroni correction for haplotypes to α = 0.05: α/2 = <0.025. †…”

“…The inclusion criteria were the presence of neutropenia, an absolute neutrophil count below 1.5 × 10 9 cells/L in two repeated tests, age under 5 years at the time of diagnosis as suggested by Fioredda et al. (2022), and the presence of anti‐neutrophil antibodies in the flow cytometric indirect granulocyte immunofluorescence test (Flow‐GIFT) as previously described (Nielsen et al., 2021). Patients with initial negative antibody screening were retested as suggested by Bux et al.…”

“…As a result of gene duplication and recombination, copy number variation (CNV) is observed, and an individual can express between zero and four different HNA‐1 alleles (Flesch & Reil, 2018). 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‐ (HNA‐1a) genotype (Nielsen et al., 2021).…”