Anti-HBV neonatal immunization with recombinant vaccine. Part II. Molecular basis of the impaired alloreactivity

HLA study was performed in 9 absolute non responder (serum titre of anti-HBsAg < 2 mlU ml 1) and 8 hyporesponder (serum antibody level between 2 and 9.9 mlU ml-1) babies who underwent, in neonatal period, HBV vaccination with Engerix B recombinant vaccine. The investigation pointed out that many of these subjects carry HLA haplotypes classically involved in autoimmune diseases: namely HLADR7; DQ2, DR4; DQ8 and DR3; DQ2. The genomic typing for DRB1, DRB3, DRB4, DRB5, DQA1, DQB1 and DPB1 genes revealed an increased frequenty of DRB1*0701; DQA1*0201; DQB1*0201 haplotype (23.5 vs 9.9% of the controls) and of DPB*0201 allele (42.3 vs 13.2% of controls). The polymorphism of Bf, CD4 an dC4B complement serum components, recognized as important "immune-function- related genes", pointed out an increased frequency of the nell allele C4AQ0 (34.3 vs 6.8% of the controls) stressing the role of F4A serum complement in response to foreign peptide. THe immunogenetic investigation has been extended to 23 responder babies (titre of anti-HBsAg > 50 mlU ml-1), vaccinated with the same trial as the poor responders. The HLA frequencies observed in this group were comparable to those of control population and, with respect to the HLA markers cited above, absolutely different from the non /hyporesponder infants. From the HLA class II sequence analysis in the group of poor-responder babies some characteristics, peculiar to autoimmune diseases, have been observed: the majority of the infants showed at least an arginine at the 52 residue of the alpha chain of DQ molecule and a non-asparitic acid at the 57 position of the DQ beta chain.