Autoimmune Disorders

HLA, Genetic Predisposition, and the Immune System

Abstract

Many diseases with autoaggressive immune components appear to have predisposing genetic factors. Such a contention is supported by the observation of an increased prevalence of many autoimmune diseases among family members and among ethnic or racial groups (1). Moreover, autoimmune diseases are more often shared among monozygotic twins than among dizygotic twins or nonrelated individuals (1,2). Ultimately, disease association with genetic factors has often been defined in terms of human leukocyte antigens (HLA), particularly those for the highly polymorphic class I and class II genes. Yet most HLA-associated diseases (which include infectious diseases and some forms of cancer) do not reveal a simple Mendelian mode of inheritance, either recessive or dominant, are only partially penetrant, and may involve a number of different HLA alleles in addition to non-HLA loci (3). Taken together, these observations indicate that autoimmune diseases have a genetic basis, but that they also have environmental components and that multiple genetic loci are probably critical to disease onset.

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