Although the specific cause of RA is unknown, there is speculation about multiple causation, which includes infection, autoimmunity, and genetic factors and also environmental and hormonal factors. The strongest evidence of an autoimmune cause is supported by the findings of rheumatoid factor (RF) in the serum of more than 80% of affected individuals. Studies in immunology have identified the appearance of a relationship between RA and the HLA system, which is made up of a series of linked genes on the sixth chromosome, indicating a genetic causative factor.

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