Distribution of killer cell immunoglobulin-like receptors genes in the Italian Caucasian population.

BACKGROUND: Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activatory receptors that are expressed by most natural killer (NK) cells. The KIR gene family is polymorphic: genomic diversity is achieved through differences in gene content and allelic polymorphism. The number of KIR loci has been reported to vary among individuals, resulting in different KIR haplotypes. In this study we report the genotypic structure of KIRs in 217 unrelated healthy Italian individuals from 22 immunogenetics laboratories, located in the northern, central and southern regions of Italy. METHODS: Two hundred and seventeen DNA samples were studied by a low resolution PCR-SSP kit designed to identify all KIR genes. RESULTS: All 17 KIR genes were observed in the population with different frequencies than other Caucasian and non-Caucasian populations; framework genes KIR3DL3, KIR3DP1, KIR2DL4 and KIR3DL2 were present in all individuals. Sixty-five different profiles were found in this Italian population study. Haplotype A remains the most prevalent and genotype 1, with a frequency of 28.5%, is the most commonly observed in the Italian population. CONCLUSION: The Italian Caucasian population shows polymorphism of the KIR gene family like other Caucasian and non-Caucasian populations. Although 64 genotypes have been observed, genotype 1 remains the most frequent as already observed in other populations. Such knowledge of the KIR gene distribution in populations is very useful in the study of associations with diseases and in selection of donors for haploidentical bone marrow transplantation.

[Diathesis and predisposition. A molecular reappraisal of the mode of reacting]. / Diatesi e predisposizione. Una rivisitazione molecolare del modo di reagire.

The identification of the causes of important infectious and hereditary diseases became scientifically clear in the last years of the nineteenth century and in the first years of the twentieth. Through many centuries, the lack of etiologic knowledge regarding diseases has extraordinarily enhanced the value of the concept of predisposition so that "diathesis" helped to "explain" many forms of morbidity. Several discoveries as to the real "causes" of diseases, however, led to a critical downgrading of its value. But in-depth knowledge regarding the proteins controlled by genes of the "major histocompatibility complex" (MHC, HLA) in man was followed, a few years later, by the demonstration of the fact that carriers of particular alleles are exposed to higher risks of contracting certain diseases than non-carriers of these molecules. A new key for interpretation-this time, a genetic and molecular one-was thus offered for the concept of "predisposition". Actually, man's HLA-associated molecular individuality induces and causes an extraordinarily personal way of reacting to various stimuli. An obvious consequence of this is not only that man, having become aware of his "molecular uniqueness" (which is significantly HLA-related), can view himself as a "biological Ego" but, most of all, that some of his predispositions towards becoming ill may be ascribed to some of his individual molecular characterizations. Thus, the onset and the course of many diseases would be viewed as the effect of a given "way of reacting". This could be recognized as the true essence of diathesis, 18 centuries after Galen.

Human leukocyte antigen class II and III alleles and severity of hepatitis C virus-related chronic liver disease.

Hepatitis C outcome is likely related both to viral factors and host's immune responses. We correlated the severity of liver disease with human leukocyte antigen (HLA) genes (C4A, C4B, TNFA, TNFB, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, TAP1, and TAP2) in three groups of subjects: 99 patients with chronic hepatitis, 41 asymptomatic carriers, and 179 uninfected controls. Patients with grade/stage 3 to 4 hepatitis significantly differentiated for their low frequency of alleles TNFB*1, DRB1*1104, and DRB3*03, which had a protective role, and high frequency of allele DRB1*1001, which was associated with disease severity. HLA-DRB*11 subtypes were differentially distributed: DRB1*1104 was most frequent in carriers, whereas DRB1*1101 was more frequent in patients. The TAP1C,2A haplotype was also underrepresented in patients with respect to controls. Finally, a decrease of heterozygous subjects was observed in patients with respect to carriers at the DQB1 locus. Multivariate analysis by correspondence analysis and multiple logistic regression indicated that age, sex, and hepatitis C virus (HCV) type were the strongest risk factors; however, some immunogenetic variables (TNFB*1, DRB1*1104, and DRB3*03) showed an independent contribution, especially in comparing patients with extreme manifestations of disease. The involvement of different genes in various HLA subregions suggests that anti-HCV responses are modulated by a complex gene interplay rather than by single alleles.