Genetic regulation of the impaired immune response to hepatitis-B vaccine associated with low TCR density in end stage renal disease patients: contribution of complement C4 and factor B alleles.
We have studied the relationship between T-cell receptor (TCR) density, genetic factors and the specific immune response in 153 end stage renal disease (ESRD) patients on haemodialysis immunised with HBsAg vaccine. One-hundred and nineteen patients raised a protective (> 10 U/ml) antibody response to hepatitis-B vaccination (responder, R), while 34 patients were found to be non-responders (NR). The density of the T-cell receptors was determined by flow cytometry. Proliferation of the T-cells induced by autologous monocytes presenting HBsAg was also measured and expressed as a stimulation index (SI). MHC class I, II and III alleles of the patients were also determined. The densities of TCR/CD3 receptors in NR patients were found to be significantly decreased as compared to the R patients (189 +/- 22 vs. 282 +/- 58 arbitrary units, P = 1.3 x 10(-7). TCR/CD3 receptor densities were found to be strongly associated (Spearman correlation coefficient: 0.84, P < 0.000001) with the SI values. Both parameters were found to be under dual genetic control: (a) very low density of the TCR/CD3 receptors and very low SI were found mainly in NR patients carrying HLA-A1, HLA-B8 and HLA-DR3 alleles; and (b) TCR/CD3 densities and function in R group were found to be significantly lower in carriers than in non-carriers of two MHC class III complement protein alleles: C4A*6, and Bf*F. Non-responsiveness to hepatitis-B vaccination was found to be associated with extremely increased neopterin levels. These findings indicate that both genetic and acquired factors contribute to the hepatitis-B vaccination failure in ESRD patients.
Kramer
J
J
National Institute of Haematology and Immunology, Membrane Biology and Immunopathology Research Group, Hungarian Academy of Sciences, Budapest, Hungary.
Stachowski
J
J
Barth
C
C
Ujhelyi
E
E
Tarján
V
V
Sulowicz
W
W
Füst
G
G
Baldamus
C A
CA
D000483:Alleles; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D003181:Complement C4 / Q000235:genetics*; D011415:Complement Factor B / Q000235:genetics*; D006510:Hepatitis B Antibodies / Q000096:biosynthesis*; D006514:Hepatitis B Surface Antigens / Q000276:immunology / Q000494:pharmacology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000235:genetics; D019798:Neopterin / Q000097:blood; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D006435:Renal Dialysis
D017252:CD3 Complex; D003181:Complement C4; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011948:Receptors, Antigen, T-Cell; D019798:Neopterin; D011415:Complement Factor B