HL-A antigens: Association with disease

Vladutiu, Adrian O.; Rose, Noel R.

doi:10.1007/bf01564070

Cited by 40 publications

(5 citation statements)

References 128 publications

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“…There is known clustering within fam ilies of certain autoimmune diseases, e.g., of the thyroid gland and stomach, and also of autoantibodies associated with these diseases [11], and there are several examples of con cordance of autoimmune thyroid disease in monozygous twins [32], Such studies imply that these diseases are the result of a specific genetic defect in regulation of immune toler ance to a limited group of autoantigens, rather than a general defect in tolerance. Moreover, a number of immunopathic dis eases, including some of autoimmune char acter, show associations with HLA antigens, particularly those of the second series, notably HLA-A3, B7, Bwl5 and B27; this area has been the subject of detailed reviews [10,33,47].…”

Section: Mhc-linked Genetic Controlmentioning

confidence: 99%

Genetic Control of Immune Responsiveness in Man

Mackay¹,

Whittingham²,

Tait³

1977

Vox Sanguinis

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Interest in immunogenetics originated from two streams: (a) histocompatibility in mouse and man, and (b) inheritance of specific immune responses in the guinea pig and mouse. In the mouse, there are genes associated with the major histocompatibility complex (MHC) which (i) code for antigens determining allograft responses and mixed lymphocyte reactions, (ii) control responses to certain antigens (Ir genes), and (iii) code for cell-surface antigens which elicit specific antisera (anti-la). In man, there is genetic control, in part X-linked, over levels of immunoglobulins and immunoglobulin classes. Evidence for MHC-linked genetic control is derived from immune responses to (i) micro-organisms, (ii) pollen antigens, (iii) food antigens, (iv) vaccines, (v) innocuous test antigens, and (vi) autoantigens. Some evidence exists for allotype-linked genetic control. Practical aspects concern influences of the MHC on susceptibility to disease, within individuals and populations.

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Section: Mhc-linked Genetic Controlmentioning

confidence: 99%

Genetic Control of Immune Responsiveness in Man

Mackay¹,

Whittingham²,

Tait³

1977

Vox Sanguinis

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“…While heredity in a heterogeneous population like humans is only a minor factor in determining the risk of developing an autoimmune disorder (usually there is less than 50% concurrence even in identical twins), inbreeding of animals has made it a determining factor, not only in rats and mice, but sometimes in guinea pigs and beagle dogs. Our initial discovery that the major histocompatibility complex is the source of the main susceptibility genes in thyroiditis has been established in virtually all autoimmune diseases in animals and humans (Vladutiu and Rose, 1971; Bacon et al, 1974; Vladutiu & Rose, 1974). The remaining inherited susceptibility is apportioned among a large number of genes, most of which contribute a small measure of susceptibility (Beisal et al, 1982).…”

Section: Evolutionary Imperativesmentioning

confidence: 99%

Molecular mimicry and clonal deletion: A fresh look

Rose

2015

Journal of Theoretical Biology

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In this article, I trace the historic background of clonal deletion and molecular mimicry, two major pillars underlying our present understanding of autoimmunity and autoimmune disease. Clonal deletion originated as a critical element of the clonal selection theory of antibody formation in order to explain tolerance of self. If we did have complete clonal deletion, there would be major voids, the infamous “black holes”, in our immune repertoire. For comprehensive, protective adaptive immunity, full deletion is necessarily a rare event. Molecular mimicry, the sharing of epitopes among self and non-self antigens, is extraordinary common and provides the evidence that complete deletion of self-reactive clones is rare. If molecular mimicry were not common, protective adaptive immunity could not be all-encompassing. By taking a fresh look at these two processes together we can envision their evolutionary basis and understand the need for regulatory devices to prevent molecular mimicry from progressing to autoimmune disease.

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“…In fact, as early as 1974 we were able to review the available literature and find a number of examples of possible associations (17). In retrospect, it is safe to say that essentially every human autoimmune disease seems to have some MHC bias, although it ranges from marked to minimal.…”

Section: Major Histocompatibility Complex In the Ratmentioning

confidence: 99%

The genetics of autoimmune thyroiditis: The first decade

Rose

2011

Journal of Autoimmunity

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Most of our current understanding of the genetic predisposition to autoimmune disease can be traced to experiments performed in the decade from 1971 to 1981. Chella David was a key contributor to this research. Many of these early steps came from studies of experimental autoimmune thyroiditis. This model has been especially valuable because essentially the same disease can occur spontaneously in selected strains of animals or can be induced by deliberate immunization. From a genetic point of view, the disease has been investigated in three different species: mice, rats and chickens. The same antigen, thyroglobulin, initiates the disease in all three species. Among the main discoveries were the relationship of autoimmune disease to the major histocompatibility complex (MHC), the interplay of different subregions within the MHC in promoting or retarding development of disease, the differing roles of MHC class II and MHC I class genes in induction and effector phases, respectively, and the cumulative effect of non-MHC genes, each of which represents a small addition to overall susceptibility. Other experiments revealed that genetic differences in thyroglobulin allotypes influence susceptibility to thyroiditis. Thyroid glands differed in different strains in vulnerability to passive transfer of antibody. The first evidence of modulatory genes on the sex-related X chromosome emerged. All of these genetic findings were concurrently translated to the human disease, Hashimoto’s thyroiditis, where thyroglobulin is also the initiating antigen.

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HL-A antigens: Association with disease

Cited by 40 publications

References 128 publications

Genetic Control of Immune Responsiveness in Man

Genetic Control of Immune Responsiveness in Man

Molecular mimicry and clonal deletion: A fresh look

The genetics of autoimmune thyroiditis: The first decade

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