D3.386 - Prevalence and immune mechanisms of rheumatoid arthritis in Kyrgyz highland residents

According to the WAO, rheumatoid arthritis (RA) affects approximately 1% of the population. In Central Asian countries (Kazakhstan, Uzbekistan, Kyrgyzstan, Tajikistan, and Turkmenistan), RA diagnosis rates remain under-diagnosed, especially in rural and high-altitude regions. In the Kyrgyz Republic, characterized by the presence of a large number of mountainous settlements,  altitude may impact RA prevalence.  The goal of the study was to assess the impact of altitude on the risk of developing rheumatoid arthritis in the Kyrgyz Republic, determine quantitative risk parameters and identify comorbidities that exacerbate the disease at high altitudes.

A retrospective epidemiological analysis was conducted of the medical records of patients diagnosed with RA over the past 5 years.  Two   main cohorts  of patients were compared: patients living at altitudes above 2,000 meters above sea level   and patients from lowland areas. The clinical analysis included calculation of the following parameters: relative risk (RR), relative risk reduction (RRR), risk difference (RD), standard error (SE), and 95% confidence interval (CI). Laboratory studies    included the assessment   of anti-citrullinated protein antibodies (ACPA) , rheumatoid factor (RF), and C-reactive protein (CRP) levels. Proinflammatory cytokine (IL-6, TNF-α) were assed by ELIZA method. The number of Th17 and Treg cells studied by flow cytometry method.  

Patients living at altitudes above 2,000 meters had a 3-fold increase in RR  of developing of the disease. Among the comorbidities that  worsened the   RA at high altitudes were coronary heart disease (RR = 39.34), hypertension (RR = 14.74), pyelonephritis (RR = 24.27), and gastropathy (RR = 42.28).  Levels of ACPA in patients from high-altitude regions was 23% higher and the number of Th17 cells were increased by 19%, and Treg cells  were decreased by 11%. Levels of   IL-6 and TNF-α, as well as  RF were much higher in patients from  high altitude regions.  Cold exposure   increases the risk of developing RA by 1.8 times, while air humidity above 70% was associated with an 27% increase in exacerbation rates.   

Altitude has a significant impact on the prevalence and severity of rheumatoid arthritis. High-altitude conditions, due to hypoxic and climatic factors, activate inflammatory and autoimmune mechanisms, contributing to disease progression. Comorbidities, particularly cardiovascular, nephrological, and gastrointestinal pathologies, aggravate the course of RA.