Henri Kreis

The changing relative prevalence of hepatitis C virus genotypes: Evidence in hemodialyzed patients and kidney recipients

BACKGROUND/AIMSnHepatitis C virus (HCV) infection by the genotype 1b is significantly associated with a lower rate of response to interferon alfa and with severe liver disease (cirrhosis and hepatocellular carcinoma). This may reflect different intrinsic properties of this genotype 1b and/or chronological differences in the epidemiology of HCV genotypes. To address the issue of variations in genotypes prevalence, we studied in the present report the HCV genotypes of 60 hemodialyzed and kidney recipients according to the date of hemodialysis.nnnMETHODSnAnti-HCV antibodies were tested by a second-generation assay (enzyme-linked immunosorbent assay 2 and recombinant immunoblot assay 2). HCV RNA was detected by reverse-transcription polymerase chain reaction. Genotyping was performed by hybridization of type-specific probes to the amplified product from the 5 untranslated region.nnnRESULTSnGenotype 1b accounted for more than two thirds of HCV infection in patients who underwent dialysis before 1977 but less than one third in those hemodialyzed after 1985. In contrast, other genotypes (3a, 4a, 5a) appeared in the 1980s.nnnCONCLUSIONSnThese data, obtained in an homogenous group of patients, show a changing pattern of HCV genotype prevalence over time and should be considered when discussing the potential clinical implications of HCV genetic variability.

Microchimerism frequency two to thirty years after cadaveric kidney transplantation

Understanding the mechanisms of unresponsiveness to allograft is crucial in order to induce long-term specific immune tolerance in organ recipients. An association between persistent microchimerism following allogeneic organ transplantation and donor-specific graft acceptance has recently been proposed. However, the frequency of chimerism and its relevance in long-lasting tolerance are still unclear. We studied 12 long-surviving (20-30 years) and eight recently grafted (2 years) cadaveric kidney transplant recipients for the systemic presence of donor alleles by using allele-specific genomic amplification of DRB1 and H-Y loci. This technique enabled the detection of a 1:4000 to 1:10,000 donor-recipient cell ratio. Among long-term tolerant recipients, microchimerism was observed in only one case in the peripheral blood and four cases in the skin. These chimeric patients did not differ from others by any clinical or immunologic parameter. In the 2-year tolerant patient group, skin chimerism was evidenced in only one patient who had simultaneously received kidney and liver transplants. No correlation was observed between the presence of chimerism and the number of HLA-DR alleles shared by donor and recipient. This low frequency of microchimerism raises doubts about a major role of chimerism in development of long-lasting specific tolerance following kidney allografting.

Contribution of Monoclonal Anti-T Cell Antibody in the Follow-Up and the Immunosuppressive Treatment of Renal Transplant Patients

Over the past few years considerable insight has been gained on the humoral and cellular immune reactions triggered by an allotransplanted organ. However, from a practical point of view, the immunological monitoring of patients receiving a renal allograft still remains an elusive and finally unsolved matter. By now, no simple immunological test has been described that correlates in a reliable fashion with the clinical evolution of the graft. In the particular case of renal transplantation, the situation is further complicated by the nearly exclusive use of serum creatinine to define graft rejection. In fact, creatininemia only increases when advance renal damage has occurred and is not always due to a rejection process.