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

J Med Virol. 1991 Nov;35(3):216-22. doi: 10.1002/jmv.1890350313.


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 vaccination with a standard scheme (0, 1 and 6 months) of 20 micrograms recombinant hepatitis B (HB) vaccine was significantly impaired in the IDDM patients both with respect to the number of nonresponders (25 versus 3%, P less than 0.05) and antibody titers reached (1,377 vs. 9,060 IU/L, P less than 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 markedly 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. Non-responding 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / immunology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepatitis B Antibodies / biosynthesis*
  • Hepatitis B Vaccines
  • Humans
  • Immunization
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Prospective Studies
  • Vaccines, Synthetic / administration & dosage
  • Viral Hepatitis Vaccines / administration & dosage*


  • Hepatitis B Antibodies
  • Hepatitis B Vaccines
  • Vaccines, Synthetic
  • Viral Hepatitis Vaccines