Killer cell immunoglobulin-like receptor genotype and killer cell immunoglobulin-like receptor-human leukocyte antigen C ligand compatibility affect the severity of hepatitis C virus recurrence after liver transplantation.

In 20% to 30% of infected individuals, hepatitis C virus (HCV) can cause cirrhosis and hepatocellular carcinoma, for which liver transplantation is the best treatment available. HCV re-infection is universal, and hepatitis disease recurrence occurs in most cases with a 30% probability of progression to graft cirrhosis at 5 years post-transplant. The immunological response to HCV involves natural killer (NK) cells and killer cell immunoglobulin-like receptors (KIRs), which specifically recognize human leukocyte antigen (HLA) class I antigens present on target cells. The effector functions of NK cells are influenced by inhibitory KIR interaction with self-HLA class I ligands, with HLA-C being the most predominant. This study examines the roles of KIR genotypes and their HLA ligands in both HCV disease recurrence and its progression. A total of 151 patients were included in the cohort, and their clinical details were recorded. Liver biopsies were used to define the absence/presence of recurrent hepatitis, the degree of fibrosis, and the progression to cirrhosis over a 10-year period. Mismatching of KIR-HLA-C ligands between donor-recipient pairs was associated with the recurrence of hepatitis (P = 0.008). The presence of KIR2DL3 in the recipient correlated with progression to liver fibrosis (P = 0.04). The mismatching of HLA-KIR ligands favored the progression of the recurrent hepatitis to fibrosis only in the presence of KIR2DL3 (P = 0.04). These preliminary results indicate that the KIR genotype and KIR-HLA-C ligand compatibility play roles in the recurrence and progression of hepatitis C disease in liver transplant recipients.

Complete sequencing of the HLA-A*68020102 novel allele identified in two Caucasoid families.

We describe here the isolation and the full-length sequence of the coding region of the HLA new variant at the HLA-A locus officially named A*68020102. This variant shows an 11 base pairs deletion within the 5' UTR region. The exon sequence is identical to that of A*6802 and the commercially available anti-A68 typing sera react with the antigen coded by the allele A*68020102. This variant was originally identified in two unrelated Caucasoid families because of discrepant HLA typing results between serology, Sequence Specific Oligonucleotide Probe (SSOP), and SBT. In fact, the A68 assigned by serology was undetectable with the molecular techniques. This has occurred because the deletion present in A*68020102 prevents specific amplification of HLA-A locus by some commercially available typing kits.

Luminex technology for anti-HLA antibody screening: evaluation of performance and of impact on laboratory routine.

The recent introduction of new technologies such as Luminex has provided alternative methods to the Complement Dependent Cytotoxicity (CDC) test for HLA specific antibody detection. In this study we compared the results obtained with CDC to those obtained using a Luminex method with the aim of evaluating the impact of this new technology on antibody screening policies in our transplant setting.A total of 1,421 sera, acquired from patients on the waiting list for a kidney transplant or following transplantation, were tested by both methodologies. CDC was performed using a whole lymphocyte population comprising a panel of 52 cells. The percentage panel reactive antibodies (PRA) and antibody specificity were evaluated using Lambda Scan Analysis software. For the Luminex method sera screening and identification of antibody specificity were carried out using the LABScreen Mixed and LABScreen PRA respectively. The overall concordance between the results obtained using the CDC and the Luminex methods was 85%. HLA antibody specificity was confirmed in 96% of the sera which tested positive using the Luminex system and serum positivity corresponded with a previous sensitisation event in these individuals. Using the Luminex method 18% of patients on the waiting list were considered and managed as sensitised as compared to 7% when testing with CDC alone. The Luminex method was able to detect a number of antibody specificities significantly more frequently than the CDC method and in addition the CDC method failed to detect some of the antibody specificities detected by the Luminex system. Based on this comparison study we have incorporated the Luminex methodology into our screening strategy.

Polymorphisms of TLR4 but not CD14 are associated with a decreased risk of aggressive periodontitis.

OBJECTIVE: To study whether there is an association between the frequency of functional polymorphisms in the toll-like receptor 4 (TLR4) and cluster differentiation 14 (CD14) genes and periodontitis. METHODOLOGY: Genotyping for the TLR4 single-nucleotide polymorphisms (SNPs) Asp299Gly, Thr399Ile and the CD14 SNPs -159 and -1359 was completed for subjects with periodontal disease compared with control subjects. Two disease populations were investigated: 73 subjects with aggressive periodontitis (AgP; 28 males, 45 females) and 95 males with chronic periodontitis (CP). The TLR4 and CD14 polymorphisms were determined using SNaPshot primer extension with capillary electrophoresis. Comparison of allele and genotype frequencies for each polymorphism was by Fisher's exact test or chi2 analysis. RESULTS: The TLR4 Asp299Gly genotype was present in a significantly (p=0.026) lower proportion of AgP subjects (5.5%) compared with control subjects (16.3%). The unadjusted odds ratio for the Asp299Gly genotype to be associated with AgP was 0.30, 95% confidence interval 0.10-0.91. No differences were found in the prevalence of the TLR4 Asp299Gly genotype in men with CP (18.9%) compared with an age-matched control group with no evidence of periodontitis (17%). In addition, there was no difference in the distribution of the CD14 polymorphisms in either the AgP or CP populations studied compared with controls. CONCLUSION: It is concluded that in West European Caucasians, the Asp299Gly TLR4 gene polymorphism is associated with a decreased risk of AgP but not CP. Promoter polymorphisms of the CD14 gene, however, did not influence susceptibility to inflammatory periodontitis in the population cohorts studied.