<unk>  is a systemic (whole body) autoimmune disease. Some genetic and environmental factors affect the risk for<unk> . Genetic A family history of<unk>  increases the risk around three to five times; as of 2016, it was estimated that genetics may account for between 40 and 65% of cases of seropositive<unk> , but only around 20% for seronegative<unk> .<unk>  is strongly associated with genes of the inherited tissue type major histocompatibility complex (MHC) antigen. HLA-DR4 is the major genetic factor implicated – the relative importance varies across ethnic groups. Genome-wide association studies examining single-nucleotide polymorphisms have found around one hundred alleles associated with<unk>  risk. Risk alleles within the HLA (particularly HLA-DRB1) genes harbor more risk than other loci. The HLA encodes proteins which controls recognition of self versus nonself molecules. Other risk loci include genes affecting co-stimulatory immune pathways, for example CD28 and CD40, cytokine signaling, lymphocyte receptor activation threshold (e.g., PTPN22), and innate immune activation appear to have less influence than HLA mutations. Environmental There are established epigenetic and environmental risk factors for<unk> . Smoking is an established risk factor for<unk>  in Caucasian populations, increasing the risk three times compared to non-smokers, particularly in men, heavy smokers, and those who are<unk>  factor positive. Modest alcohol consumption may be protective. Silica exposure has been linked to<unk> . Negative findings No infectious agent has been consistently linked with<unk>  and there is no evidence of disease clustering to indicate its infectious cause, but periodontal disease has been consistently associated with<unk> . The many negative findings suggest that either the trigger varies, or that it might, in fact, be a chance event inherent with the immune response.
Rheumatoid arthritis
Fibromyalgia
Reactive arthritis
Psoriatic arthritis
Rheumatism
Lupus
Inflammatory arthritis
Septic arthritis