Humoral response to recombinant hepatitis B virus vaccine at birth: Role of HLA and beyond

From 1991 to 1998 we vaccinated 4835 neonates against hepatitis B virus (HB V) and monitored their humoral response to the recombinant vaccine. In a sa mple of 184 of these babies we studied the association between HI;A class I and II genomic polymorphisms and humoral response to the vaccine and the a ssociation between the response and immune-mediated diseases. A subgroup of 96 babies also underwent HLA class III (C4A and C4B) typing. Four levels o f humoral response were identified, each with a peculiar MHC restriction. D ifferent HLA products seem to act as agonists (C4AQ0 and HLA-DQB1*02) or an tagonists (C4AQ0, HLA-DQB1*02, and HLA-DRB1*11, DQB1*0301) in Lowering humo ral response to HBV vaccine. The group of responders was characterized more for lacking "nonresponder" alleles than for having specific "responder" on es. Tolerance to HBV peptides may have clinical implications, possibly bein g a marker for babies with a genetic risk of immunopathologies, In fact, ma ny of the poor responders carried from two to four HLA-DQ alpha beta hetero dimers predisposing to insulin-dependent diabetes mellitus and celiac disea se. Two true nonresponders suffered from allergies and two slow responders had transient episodes of hyperglycemia. (C) 2000 Academic Press.