A prospective study of in vitro anti-HBs producing B cells (spot-ELISA) following primary and supplementary vaccination with a recombinant hepatitis B vaccine in insulin dependent diabetic patients and matched controls

A prospective study of the immune response after hepatitis B vaccination was carried out in 32 insulin dependent diabetes mellitus (IDDM) patients and their age and sex matched healthy controls. A sensitive, immunoenzymatic technique was used, able to detect in vitro specific antibody production by mitogen stimulated individual B cells. In‐vivo serologic response after vaccinationwith a standard scheme (0, 1 and 6 months) of 20 pg recombinant hepatitis B (HB) vaccine was significantly impaired in the IDDM patients both with respect to the number of nonresponders (25 versus 3%, P < 0.05) and antibody titers reached (1,377 vs. 9,060 IU/L, P < 0.05). The total number of in vitro IgM‐ and IgG‐class immunoglobulin producing B cells as detected by the spot‐ELISA, was found to be comparable in both groups. Specific IgG anti‐HBs (and to a lesser extent IgM anti‐HBs) showed impairment in the diabetic population as a whole. The number of IgG anti‐HBs producing B cells was mark‐ edly depressed one month following vaccination, which is probably a reflection of homing of B cells outside the circulation. Responding subjects were identified early during their vaccination by the detection of in vitro anti‐HBs production using the spot‐ELISA. Nonresponding healthy subjects and IDDM patients as a group showed a low number of IgG anti‐HBs spots, suggesting a reduced specific memory B cell frequency. In 13 of 15 hypo‐ and nonresponders with positive IgG anti‐HBs spots supplementary vaccination(s) resulted in improved anti‐HBs levels.