Hla in familial hodgkin's disease. Results and a new hypothesis

Abstract

A familial aggregate of seven cases of Hodgkin's disease (HD) has been investigated by HLA typing. Over 600 people in the immediate population (i.e. about half) have been HLA typed and haplotypes have been obtained for 95% of them. It was expected that the cases would share a particular HLA haplotype or at least that they would have one or two HLA antigens of the same series in common. However, this was not the case so no simple idea of association of HLA with HD cases was upheld. When antigen frequencies were examined in the whole population, it was found that HLA B18 increased progressively in incidence from 0.08 to 0.4 in successive groups of individuals each one more closely related to the HD cases. Similarly the community with the highest incidence of HD also had the highest incidence of B18. Thus B18, which in the world figures carries the highest relative risk, emerged as important in this study. Of four proposed interpretations of the data, we are most interested in the idea that the important HLA association is at a population level rather than at the level of the individual patient. A hypothesis, based on the concept of a "healthy carrier" for the HD agent, explains how such an association might operate. It is possible that B18-linked complement deficiency could be the basis for such a carrier state.

Multiple HLA class I and II associations in classical Hodgkin lymphoma and EBV status defined subgroups

“…An association with HLA-DR5 has been reported previously by Robertson et al in familial cHL. 31 Significant effects of HLA-A1, HLA-B8, and HLA-B18 for cHL that have been reported in previous publications [12][13][14] could not be confirmed in the total patient group in our study, whereas the previously reported association with HLA-B5 29 was borderline significant in the overall cHL group in our study. These differences might be explained by differences in sample size, patient selection, and proportion of EBV ϩ cases.…”

“…6,[12][13][14] More recently, we focused on the EBV ϩ cHL subgroup in a genetic screening study of the entire HLA region. 5 In a subsequent fine-screening analysis, we found a strong association of specific HLA-A alleles with susceptibility to EBV ϩ cHL in Dutch and English patients.…”

Incidence of familial Hodgkin's disease

“…The finding of a significant association between HD and parental consanguinity (Abramson et al, 1978) and the results of statistical analysis of data from a family in which several members had HD (Thompson, 1981) suggests an autosomal recessive HD-susceptibility gene. Case reports of HD occurring in families with known immunodeficiency disorders (McBride & Fenelly, 1977;Buehler et al, 1975;Harris et al, 1981) and the suggested association between HD and certain HLA haplotypes are consistent with the hypothesis that inherited susceptibility to HD may be determined by immune response genes (Marshall et al, 1977;Bowers et al, 1977). Recent epidemiological data suggest that HD, at least in young people, may be a rare sequel to a common virus infection.…”

Multiple Hodgkin lymphoma–associated loci within the HLA region at chromosome 6p21.3

“…3 Since an association between the human leukocyte antigen (HLA) region and HL risk was first reported in 1967, 4 studies have subsequently identified associations between both HLA class I and class II alleles and common HL (cHL) risk. [5][6][7][8][9][10] Studies to date have evaluated only specific HLA alleles and have not taken into account the existence of complex linkage disequilibrium patterns between the multiple risk loci mapping to the major histocompatibility complex (MHC) region, associations between HLA alleles at different resolution, and the need to control rigorously for population stratification. In view of the limitations of these previously published studies, we have conducted a more comprehensive analysis.…”