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. 2022 Aug;62(8):1636-1642.
doi: 10.1111/trf.17002. Epub 2022 Jul 6.

ABO, secretor, and Lewis carbohydrate histo-blood groups are associated with autoimmune neutropenia of early childhood in Danish patients

Kirstine Kløve-Mogensen  1   2 , Rudi Steffensen  1 , Tania Nicole Masmas  3 , Andreas Glenthøj  4 , Thure Mors Haunstrup  1 , Paul Ratcliffe  5 , Petter Höglund  5 , Henrik Hasle  6 , Kaspar René Nielsen  1   2
Affiliations

ABO, secretor, and Lewis carbohydrate histo-blood groups are associated with autoimmune neutropenia of early childhood in Danish patients

Kirstine Kløve-Mogensen et al. Transfusion. 2022 Aug.

Abstract

Background: Autoimmune neutropenia of early childhood (AIN) is caused by autoantibodies directed against antigens on the neutrophil membrane. The ABO, secretor, and Lewis histo-blood group systems control the expression of carbohydrate antigens and have previously been linked to autoimmune diseases. We aimed to investigate the association between genotypes and the risk of AIN in Danish patients.

Study design and methods: One hundred fifty-four antibody-positive AIN patients were included. Controls (n = 400) were healthy unrelated Danish blood donors. Molecular determination of ABO, secretor (FUT2), and Lewis (FUT3) genotypes were determined using real-time polymerase chain reaction (qPCR) or Sanger sequencing to infer the prevalence of Lewis antigens (Lea and Leb ) and secretor (SeSe or Sese) or nonsecretor (sese) phenotypes.

Results: Blood type O was more common in controls (46.8%) than in AIN patients (36.4%) (OR = 0.65; p = 0.028). Secretors of H Leb antigens were less frequent among AIN patients (25.2%) than controls (35.0%) (OR = 0.62; p = 0.037).

Discussion: ABO blood group antigens and the secretion of these antigens are associated with a diagnosis of AIN. The mechanism underlying the association between autoimmunity and interaction among ABO, secretor, and Lewis genotypes has not yet been elucidated, but several studies indicate a connection to the gut microbiota.

Keywords: AIN; Lewis; histo-blood group; polymorphisms of FUT2 and FUT3; secretor status.

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Conflict of interest statement

The authors have disclosed no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Summary of glycoconjugates profiles related to histo‐blood systems ABO, secretor and Lewis. Adapted from Barbé et al. 2018. FUT2 and FUT3 fucosyltransferases catalyze the linkage of fucose to the Type 1 chain precursor, creating H‐type 1 antigen. Glucosyltransferases specific for blood types A (GTA) and B (GTB) catalyze the linkage of N‐acetylgalactosamine or galactose to the antigen. The addition of fucose to N‐acetylglucosamine by FUT3 results in Lewis antigens
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