Hepatitis and Australia Antigen: Autosomal Recessive Inheritance of Susceptibility to Infection in Humans

Abstract

Abstract.-Examples of inherited susceptibility to infection controlled by genes segregating at one or a small number of loci have been identified in lower animals. In this study we report data on what appears to be a similar situation in humans. "Australia antigen" is an antigen found in the sera of patients with acute and chronic hepatitis, and it may actually be a form of virus. It is very common in many tropical areas, and people in these areas having the antigen appear to be hepatitis carriers. The antigen is detected by immunodiffusion in agar gel (Ouchterlony method). Individuals with the antigen are designated Au(1) and those without it Au(0). Family studies involving 1797 different individuals residing on the island of Bougainville are consistent with the hypothesis that susceptibility to chronic infection with the "antigen" is controlled by an autosomal recessive gene (Au'). This confirms the conclusions previously arrived at from similar (but less extensive) studies on the island of Cebu. Individuals with this inherited susceptibility do not ordinarily have overt manifestations of hepatitis.The sign test was used to determine family clustering. Segregation analysis was performed by the method of C. A. B. Smith. In the 41 Au(0) X Au(0) matings, 53.8 recessives were expected in the offspring and 56 were seen (0.7 > p > 0.5). In the Au(1) X Au(0) matings, 40.1 recessives were expected and 42 were seen (0.7 > p > 0.5). The Au(0) X Au(0) matings were also analyzed by the method of Li and Mantel, in which the recessive ratio of 0.25 is expected by the genetic hypothesis. The values observed were 0.2527 for the Bougainville study and 0.2461 for the Cebu study.Inherited resistance and susceptibility to infection has been described in several animal species. There is a single gene-controlled factor which prevents infection of mice by a group of related viruses including yellow fever, West Nile fever, Japanese B encephalitis, and others but does not prevent infection with other viruses.1 Gowen2 has described inherited resistance to bacterial infection in mice and has emphasized the specific nature of the resistance which develops. There is evidence for inherited susceptibility to several forms of virus-induced neoplasms in animals. These include polyoma virus in mice,3 in which two or three independent genes may be involved in the determination of resistance;4 mammary tumor in mice;5 leukemia in mice, where the inherited factor appears to be related to the histocompatibility locus;6 Rous sarcoma;7 fowl leucoses;8 and others. In humans, several inherited diseases carry with them an increased susceptibility to infection; for example, patients with the 1108

Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence

“…The association of the IL-10RB*E allele with viral clearance is consistent with amplified transduction of the IFN-signal, leading to more efficient viral clearance. The alternative explanation, that the IL-10 signal is amplified, is harder to reconcile with the immunoregulatory role of this cytokine and the requirement for a strong Th1 response to mediate viral elimination Forty years ago, pedigree analysis of HBsAg positivity in the Philippines (25) and then elsewhere (26) supported an autosomal recessive basis for susceptibility to carriage, and we present the mapping and identification of a major locus for this phenotype. Studies of other infectious diseases suggest that susceptibility to HBV carriage is likely to be generally highly polygenic, consistent with our finding that the region of strongest linkage in a genomewide scan includes two susceptibility genes with related functions.…”

Clinical and pathological study of asymptomatic HBsAg carriers in Chile.

“…The number of these asymptomatic carriers varies from one country to another (Prince, 1970;Salzano et al, 1970) and depends on many factors such as the social behaviour of the population (Mazzur and Jones, 1977), drug addiction (Cherubin et atl., 1970), use of commercial blood (Alter et al, 1975), and family clustering (Blumberg et al, 1969;Velasco et al, 1973;Szmuness et al, 1975 ).…”

Preliminary Communication: Familial Accumulation of Carriers of Au Antigen

“…Since Blumberg first presented his genetic hypothesis that the Au-antigen carrier state was inherited as an autosomal recessive trait the main data have come from two groups only, ie, that of Blumberg himself (Blumberg et al, 1966 and1969) and that of Carbonara et al (1970). It is amazing that after 10 years there seems still to be great controversy about the significance of familial clustering of the carriers of Au antigen.…”