The Impact of Geographic Demography on Autoimmune Severity: A Cross-Sectional Comparison of Rheumatoid Factor and Anti-Citrullinated Protein Antibody Profiles with Clinical Disease Indices in Rural and Urban Punjab

Aim of Study: To compare the serological profiles (Rheumatoid Factor and Anti-Citrullinated Protein Antibodies) and clinical disease severity indices between rural and urban patients with Rheumatoid Arthritis in the Punjab region of Pakistan, and to determine whether geographic demography independently predicts autoimmune severity. Study Duration: March 2024 to March 2025 Study Place: Aziz Fatima Medical College, Faisalabad, Pakistan Methodology: This cross-sectional comparative study enrolled 320 consecutive patients diagnosed with Rheumatoid Arthritis according to the 2010 ACR/EULAR classification criteria. Participants were stratified into rural (n=160) and urban (n=160) cohorts based on residential history of ≥10 years. Demographic data, clinical characteristics, and treatment history were recorded. Venous samples were collected for Rheumatoid Factor (RF) and Anti-Citrullinated Protein Antibody (ACPA) quantification using ELISA. Disease activity was assessed using the Disease Activity Score 28 (DAS28-ESR), while functional impairment was measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI). Radiographic damage was evaluated using the Larsen Score. Statistical analysis employed independent t-tests, Mann-Whitney U tests, chi-square tests, and multivariate linear regression. Results: Rural patients demonstrated significantly higher serological positivity rates compared to urban patients (RF: 91.3% vs. 78.1%, p=0.002; ACPA: 88.8% vs. 74.4%, p=0.001). Mean RF titers (185.4±98.2 IU/mL vs. 112.7±76.5 IU/mL, p<0.001) and ACPA levels (168.3±87.6 U/mL vs. 94.2±69.8 U/mL, p<0.001) were markedly elevated in the rural cohort. Rural residents exhibited higher disease activity (DAS28: 5.8±1.2 vs. 4.6±1.1, p<0.001), greater functional disability (HAQ-DI: 1.8±0.6 vs. 1.2±0.5, p<0.001), and more advanced radiographic damage (Larsen Score: 34.7±15.3 vs. 21.4±12.8, p<0.001). Multivariate regression identified rural residence as an independent predictor of higher DAS28 scores (β=0.42, p<0.001) after adjusting for age, gender, disease duration, and treatment adherence. Conclusion: Rheumatoid Arthritis patients residing in rural Punjab exhibit more severe autoimmune profiles with higher serological titers and greater clinical disease activity compared to their urban counterparts. These disparities appear independent of traditional demographic factors and may reflect differential environmental exposures, healthcare access barriers, or occupational risk factors prevalent in rural settings.