Rheumatoid Arthritis: Causes

Pathogenesis (disease development)

Rheumatoid arthritis (RA) involves the immigration of inflammatory cells – macrophages and T lymphocytes – into the synovial membrane (inner lining of the joint capsule) and the release of proinflammatory (inflammation-promoting) cytokines such as interleukin-1b and TNF-α – tumor necrosis factor alpha – which contribute significantly to joint destruction. It is not yet scientifically clear which causes are responsible for this chronic inflammatory process. It is assumed that it may be an autoimmune disease. In some cases, a genetic predisposition (disposition) with HLA-DR4 expression can be demonstrated. In chronic inflammation, so-called innate lymphoid cells (ILC2s) have a central role in the immune system to stop inflammation. In patients with rheumatoid arthritis, these are in a kind of hibernation. ILC2 activation is mediated by interleukin-9 (IL-9). Rheumatoid arthritis (RA) is also thought to be the body’s response to infection with an as yet unidentified pathogen – mycoplasma, Epstein-Barr virus (EBV), cytomegalovirus (CMV), parvovirus and rubellavirus are suspected. Because rheumatoid arthritis occurs throughout the world, it has been hypothesized that the infectious agent should also be present worldwide.

Etiology (causes)

Biographic causes

  • Genetic burden – in 1st-degree relatives of individuals with rheumatoid arthritis, the risk is increased approximately 4-fold
    • Genetic risk dependent on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • Genes: CD40, CTLA4, PTPN22, RSBN1, STAT4
        • SNP: rs2476601 in the gene PTPN22
          • Allele constellation: AG (1.94-fold).
          • Allele constellation: AA (3.76-fold)
        • SNP: rs3789604 in the gene RSBN1
          • Allele constellation: GT (1.55-fold).
          • Allele constellation: GG (1.73-fold)
        • SNP: rs7574865 in the gene STAT4
          • Allele constellation: GT (1.3-fold).
          • Allele constellation: TT (1.69-fold)
        • SNP: rs4810485 in the gene CD40
          • Allele constellation: GT (1.15-fold).
          • Allele constellation: TT (1.32-fold)
        • SNP: rs3087243 in the gene CTLA4
          • Allele constellation: AG (1.15-fold).
          • Allele constellation: AA (1.32-fold)
  • Lack of breastfeeding – Breastfeeding for 12 months was associated with a lower risk of the child developing rheumatoid arthritis in one study

Behavioral causes

  • Nutrition
    • High intake of the omega-6 fatty acid arachidonic acid (animal foods such as pork and pork products and tuna).
    • Low intake of long-chain polyunsaturated fatty acids (PUFA); regular consumption of one fish meal per week compared to no fish per week resulted in 29% risk reduction for rheumatoid arthritis
    • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
  • Consumption of stimulants
    • Coffee – significant increase in the rate of seropositive rheumatoid arthritis with the increase in coffee consumption.
    • Tobacco (smoking) – cigarette smoking has been shown to be associated with increased rates of disease; higher risk of seropositive RA
  • Physical activity
    • Physical inactivity
  • Overweight (BMI ≥ 25; obesity).

Disease-related causes

  • Malalignment of the joints – e.g., knock knees or bow legs.
  • Metabolic disorders – eg diabetes mellitus, gout.

Environmental pollution – intoxications (poisonings).

  • Men with occupational contact with inorganic dusts or vibrations – such as those that occur when operating jackhammers – showed a higher risk of rheumatoid arthritis, according to a Swedish study. Silica dusts in particular are suspected to be the cause. Women who worked as graphic artists or in color printing also had an increased risk

Other causes

  • Blood transfusions – individuals who had received transfusions were at increased risk, according to studies