ANTI-HBV NEONATAL IMMUNIZATION WITH RECOMBINANT VACCINE .2. MOLECULAR-BASIS OF THE IMPAIRED ALLOREACTIVITY

HLA study was performed in 9 absolute non-responder (serum titre of an ti-HBsAg < 2 mlU ml(-1)) and 8 hyporesponder (serum antibody level bet ween 2 and 9.9 mlU ml(-1)) babies who underwent in neonatal period, HB V vaccination with Engerix B recombinant vaccine. The investigation po inted out that many of these subjects carry HLA haplotypes classically involved in autoimmune diseases: namely HLADR7:DQ2, DR4:DQ8 and DR3;D Q2. The genomic typing for DRB1, DRB3, DRB4, DRB5, DQA1, DQB1 and DPB1 genes revealed an increased frequency of the DRB10701; DS2A1*0201; D QB10201 haplotype (23.5 vs 9.9% of the controls) and of DPB*0201 alle le (42.3 vs 13.2% of controls). The polymorphism of Bf. C4A and C4B co mplement serum components, recognized as important ''immune-function-r elated genes'', pointed out an increased frequency of the null allele C4AQO (34.3 vs 6.8% of the controls) stressing the role of C4A serum c omplement component 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 pool res ponders. 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 rite HLA class II sequence analysis in the group of poor-responder bab ies some characteristics peculiar to autoimmune diseases, have been ob served: the majority of the infants showed at least an arginine at the 52 residue of the alpha chain of DQ molecule and a non-aspartic acid at the 57 position of the DQ beta chain. These data highlight that the impaired responsiveness to HBV vaccination is able to select children sharing the immunogenetic background of people prone to autoimmune co nditions.