Significance of the differences in the prevalence of anti-HLA antibodies in matched pairs of mother’s and cord blood

• Anti-HLA class-I and -II IgG in native sera and their purified IgG of matched pairs of mother’s (MB) and umbilical cord blood (CB) using single antigen bead assay on a Luminex platform.
• In 2 cases, no anti-HLA-I IgG were found in either MB or CB. Four MB cases displayed polyreactive anti-HLA IgG, with no or low reactivity by the corresponding CB.
• Anti-HLA-I IgG in cases 3–6/11/12 and anti-HLA-II IgG in cases 1/3/4/6/8/11–13 were restricted to CB, with low or no reactivity in MB.
• The transplacental transfer of IgG from mother to fetus, commonly observed with anti-microbial IgG, is infrequent with anti-HLA IgG.
• CB contains anti-HLA IgG antibodies not found in the blood of mother, possibly due to de novo synthesis by the fetus.

The presence of IgG against pathogens in the cord blood (CB) of vaccinated mothers is attributed to transplacental transfer. However, previous studies using lymphocytotoxicity assay showed anti-HLA IgG in mother’s blood (MB) but not in CB, perhaps due to non-transfer of anti-HLA IgG or assay limitations in detecting anti-HLA IgG. Anti-HLA IgG of native and purified sera of 16 MB and CB pairs were measured using an array of microbeads coated with HLA-I/-II molecules on a Luminex platform. Two cases showed no anti-HLA-I IgG in either MB or CB; four MB cases displayed polyallelic HLA-reactive IgG, with negligible or no reactivity by the corresponding CB sera. Notably, anti-HLA-I reactivity in cases 3–6/11/12 and anti-HLA-II reactivity in cases 1/3/4/6/8/11–13 were restricted to CB, with lower or no HLA-reactivity in MB. Mothers’ HLA typing is done for HLA-A*, HLA-B* and DRB1* alleles. The mother in case 14 carried DRB1*11:01, the allele-reactive IgG is seen in both native and the purified fraction of sera of MB but not in CB. Also in cases 15 (DRB1*01:01) and 16 (B*49:01 and DBR1*07:01), the allele-reactive IgGs are seen in both native and purified fractions of MB but not in CB confirming the earlier reports on the absence of materno-fetal transfer of anti-HLA IgG. However, the mother of case 6 is homozygous for DRB1*03:01 and the allele-reactive IgG occurred in both MB and CB, confirming the presence of anti-HLA autoantibodies. In Case 13, the mother (HLA-A*24 and HLA-A*52) and CB carried allele-reactive IgG in both native and purified sera, indicating the possible occurrence of transplacental transfer of the IgG. Further confirmation is restricted by the paucity of detailed molecular HLA typing for both the parents and fetuses. While 37.5% of the native IgG in CB and 18.8% in MB showed DRB3*03:01 reactivity, 100% of purified IgG from both CB and MB showed anti-DRB3*03:01 and anti-DPA1*02:01\ DPB1*23:01 antibodies. Several CB cases showed high-prevalence IgG reacting to a single allele of HLA-I and/or HLA-II with minimal or no cross-reactive IgG in CB or in the MB, suggesting the presence of de novo antibodies, possibly against non-inherited maternal HLA or inherited parental HLA haplotypes by the fetus.