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

Judit Kramer, Józef Stachowski, Claudia Barth, Eszter Újhelyi, Veronika Tarján, Wladyslaw Sulowicz, George Füst, Conrad A. Baldamus

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)13-19
Number of pages7
JournalImmunology letters
Volume59
Issue number1
DOIs
Publication statusPublished - Oct 1 1997

Keywords

  • Genetic regulation
  • Hepatitis-B vaccine
  • Low TCR density

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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