CD94 and NKG2 are members of the NK cell receptor families, and are encoded in the natural killer gene complex (NKC) on human chromosome 12p12-13, one of the candidate chromosomal regions for rheumatic diseases. To examine a possible association between variations in CD94 and NKG2 genes and genetic susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), we carried out a systematic polymorphism screening of NKG2-A (KLRC1), NKG2-C (KLRC2) and CD94 (KLRD1) genes on a population basis. In NKG2-A, previously considered to be highly conserved, 10 polymorphisms in the noncoding region and introns, as well as one rare variation leading to an amino acid substitution within the transmembrane region, c.238T4A (Cys80Ser), were detected. In NKG2-C, in addition to the previously described two nonsynonymous substitutions, c.5G4A (Ser2Asn) and c.305C4T (Ser102Phe), two polymorphisms were newly detected in the noncoding region. In CD94, only one single nucleotide substitution was identified in the 5 0 untranslated region. When the patients and healthy individuals were genotyped for these variations, no significant association was observed. However, although statistically not significant, NKG2-A c.238T4A (Cys80Ser) was observed in three patients with RA, but in none of the healthy individuals and the patients with SLE. Unexpectedly, in the process of polymorphism screening, we identified homozygous deletion of NKG2-C in approximately 4.3% of healthy donors; under the assumption of Hardy-Weinberg equilibrium, the allele frequency of NKG2-C deletion was estimated to be 20.7%. These results demonstrated that, although human NKG2-A, -C and CD94 are generally conserved with respect to amino acid sequences, NKG2-A is polymorphic in the noncoding region, and that the number of genes encoded in the human NKC is variable among individuals, as previously shown for the leukocyte receptor complex (LRC), HLA and Fcg receptor (FCGR) regions.

Herpes zoster is a common disease caused by reactivation of the varicella zoster virus (VZV). In a small number of herpes zoster patients, pain persists beyond 4 weeks or more after healing of vesicular eruptions; this condition is termed postherpetic neuralgia (PHN). Positive associations of human histocompatibility leukocyte antigens (HLA) class I antigens, A33 and B44, with PHN in the Japanese population have been reported. Our hypothesis is that susceptibility genes to PHN might exist in the HLA region and the study objective is to further examine possible associations of genes in HLA class I, II and III regions, HLA-A, -B, -DRB1, tumor necrosis factor a (TNFA) promoter, and a natural killer cell activating receptor, NKp30 polymorphisms with PHN. Although TNFA or NKp30 in the class III region had been considered as a candidate locus, we found no associations of TNFA promoter or NKp30 polymorphisms with PHN in this study. We demonstrated that HLA-A*3303, -B*4403 and -DRB1*1302 alleles were significantly associated with PHN (P ¼ 0.0007 for A*3303, P ¼ 0.001 for B*4403 and P ¼ 0.001 for DRB1*1302). The frequency of the HLA-A*3303-B*4403-DRB1*1302 haplotype was also significantly higher in the PHN patients than in the healthy controls (P ¼ 0.0039). Our results suggest that this haplotype might be related to the pathogenesis of PHN.

We investigated the relationship between the frequency of the common cold and the conditions of the body's immune system among members of a generally healthy population. Self-reporting questionnaires on the frequency of the common cold and on fatigue and stress conditions were administered to a total of 67 healthy individuals aged 22 to 50. The activities of natural killer (NK) cells, which were determined by Eu3+-DTPA release assay, and of NK cell members in the peripheral blood of the subjects were phenotypically (CD3 CD16 + CD56 +) analyzed with three-color flow cytometry. The results showed that the frequency of the common cold was significantly correlated with NK activity and NK subset (CD3-CD16 + CD56 ~) frequency (r=-0.34 and -0.47 respectively, P<0.01). After adjusting for age, the mean NK subset (CD3 CD16+CD56 § significantly differed (F=3.384, P<0.05) among the four frequency groups for the common cold, and the frequencies of the common cold were significantly different among the four stress/fatigue groups (F= 8.016, P< 0.001) for the males, as evaluated by ANCOVA. These results indicate that conditions of high stress and fatigue may increase the chance of catching the common cold due to a decrease in activities of NK cells.