Risk factors for rheumatoid arthritis

Abstract

Both genetic and environmental factors contribute to the development of rheumatoid arthritis (RA). A long-term latent process often precedes the onset of arthritis. Hence, the ultimate causes of RA cannot be clarified by studying only the inflamed joints. Longitudinal studies focusing on risk factors are crucial in approaching the true aetiology. At present, most information gained from epidemiological studies is contradictory or vague. For instance, there is no consensus concerning the long-term effects of pregnancy or the putative protective role of oral contraceptives. There is no doubt that diet plays a role, but no specific nutrient has proved to be either protective or deleterious. Smoking is the only environmental risk factor that has been firmly verified epidemiologically for RA. It can be reasonably regarded as a contributory cause of RA. Studying the immunological effects of exposure to cigarette smoke may offer an opportunity to combine information from basic and epidemiological research to clarify the causal chains leading to RA.

Prolactin and Autoimmunity

“…According to one case-control study, much of the increased RA risk during the postpartum period seems to be associated with lactation. A possible explanation for the association with breastfeeding is its relationship with HPRL [82]. Studies of PRL levels in non-pregnant patients with RA have not consistently demonstrated elevated levels.…”

Smoking is a risk factor for multiple sclerosis: a metanalysis

“…No case-control difference in smoking was detected, but there is just a statement to this effect without further supporting information. Furthermore, rheumatoid arthritis has a known association with smoking [13]; (iii) a study from Ferrara, Italy [14], containing 104 cases and 150 controls which showed no significant difference for 'smoking and drinking in adolescence', but further details are not given; (iv) two positive studies from Spain with insufficient data for analysis as described above [6,7]; (v) a negative study from North England [2], already described; (vi) the initial study from Oxford [3], which was supplemented by a later publication [4].…”

“…Smoking is claimed to be linked to autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosis, Grave's disease and Crohn's disease [13,18]. Nicotine may increase blood Á brain permeability to allow entry of abnormal T cells, or tobacco smoke may poison the central myelin, as it does in tobacco amblyopia, possibly by elevation of blood levels of its metabolite, thiocyanate.…”

Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles

“…[1][2][3][4][5][6][7] The most important genetic risk factor for rheumatoid arthritis is the presence of HLA class II alleles which share the conserved amino acid sequence called the shared epitope. 8 These shared epitope residues constitute a part of the antigen-presenting binding site.…”