Heat shock proteins: the missing link between hormonal and reproductive factors and rheumatoid arthritis?

Article Abstract:

Hormones and childbirth are known to influence disease activity and progression of rheumatoid arthritis, but they may also affect the actual occurrence of this disease. Some aspects of these hormonal and reproductive influences are controversial, however. Possible mechanisms of interaction between these factors and rheumatoid arthritis are described. Rheumatoid arthritis is approximately three-fold more prevalent in women, and is especially prevalent in the later reproductive years, before declining with age. Nulliparity (not having given birth) is associated with a greater risk of developing rheumatoid arthritis than having had one or more pregnancies. The risk of severe disease is reduced in women who have used oral contraceptives. Heat shock proteins are stress proteins that have similar structures whether found in humans, bacteria or other organisms, and their production is stimulated by hormones, such as the female sex hormones. Injection with a heat shock protein, a technique similar to vaccination, protected animals against experimental induction of arthritis. Lymphocytes are immune cells important in fighting infection, and may be activated following exposure to the agent that triggers rheumatoid arthritis. T lymphocytes that cross-react with molecules within the joint may underlie many of the disease processes of rheumatoid arthritis. Exposure of T cells to small amounts of molecules can induce T cell tolerance to the molecules. Consideration of these data led to the following argument. Immunological tolerance may persist in individuals who do not develop rheumatoid arthritis, and this probably involves a state of immunosuppression, similarities of molecules from host and triggering agent, and the involvement of T lymphocytes. Pregnancy, with its 1,000-fold increased level of estrogens, may elicit production of high levels of heat shock proteins; this may also occur during oral contraceptive use. Production of heat shock proteins may allow the immune state to become tolerant to these proteins and to the purportedly similar triggering agent of rheumatoid arthritis. Fetal heat shock proteins may also alter immune system reactivity. Gaps exist in this hypothesis, but it deserves further study. (Consumer Summary produced by Reliance Medical Information, Inc.)

Heat shock proteins, Hormones, Sex, Sex hormones

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HLA typing in families with multiple cases of rheumatoid arthritis

Article Abstract:

The HLA (human leukocyte antigen) system of cell-surface antigens (molecules capable of provoking an immune response) is similar to the blood group ABO antigens in that subtle differences in these molecules, coded for by the DNA in genes, identify an individual's cells as his own, immunologically speaking, and provoke graft rejection after transplantation. Certain HLA subgroups are strongly related to particular diseases, such as diabetes. Studies of some families have shown a relationship between frequent cases of rheumatoid arthritis (RA) and the subgroup HLA-DR4, while in some ethnic groups, HLA-DR1 is linked to RA instead. Whether the proteins made from the sequences of DR genes or the DR genes themselves are linked to other genes predisposing to RA is uncertain. Complete HLA typing was done in 31 RA patients from 14 families with multiple occurrences of RA, as well as in 42 healthy relatives. Class I antigens, HLA-A, -B, and -C were not more prevalent in patients. The class II antigens DR1 occurred in 32 percent of patients and in 12 percent of healthy subjects, while DR4 occurred in 48 percent and 28 percent, respectively, with the increased frequencies in patients being significant. These results were combined with those from other reports, and analysis revealed that DR1 and DR4 have a dominant influence in the inheritance of RA. The data suggest that some DR antigens may play a direct role in the development of RA. HLA antigens did not correlate with medical variables such as disease severity. Only 68 percent of the patients in this study had DR1 or DR4, suggesting that about one third of RA patients may have a type of disease which is independent of HLA factors. (Consumer Summary produced by Reliance Medical Information, Inc.)

Genetic aspects, HLA histocompatibility antigens, HLA antigens

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