Aim

Although the pathogenesis of this inflammatory autoimmune disorder has not been fully elucidated, rheumatoid arthritis (RA) is now understood as an entity with a strong genetic component. Numerous contrary reports have emerged in this aspect. Cross-sectional, unbiased prospective population studies are essential in order to define such associations at the molecular basis. Also, one needs to explore the fact that, whether there is a difference in the HLA associations between community and clinical based RA.

Methods

Under the aegis of APLAR, the first Indian COPCORD survey was conducted in village Bhigwan (Pune District) in 1996 followed by a well-planned ongoing community driven COPCORD program till 2004. After interviewing 6034 villagers in the initial 1996 census survey 774 cases (Phase 1) reporting RMS (Rheumatic musculoskeletal pains) were identified. Laboratory investigations were done on 392 cases during the survey. The HLA DRB1 profile of 156 individuals including 57 cases with inflammatory arthritis (IA), and 99 unaffected individuals from the same village who served as healthy controls was performed. HLA DRB1 alleles were determined by PCS-SSOP typing systems Phenotype frequencies were calculated using Odds Ratios with 95% confidence intervals.

Results

HLA DRB1

None of the DRB1 types were significantly associated with RF and erosions. No association of RA (p>0.05) with the shared epitope (SE) bearing alleles (HLA DR 1/4/10) alleles was observed. Although, the frequency of DRB1 10 was found to be higher (30%) in the inflammatory group as compared to the control group (20%). By contrast, in one hospital based study (unpublished) conducted by us, 52 patients from our referal OPD were typed for HLA DRB1 alleles and compared with 77 healthy controls. The results of the latter showed an increase in the SE bearing alleles (56%; OR: 2.44; CI :1.19-4.99) with a fairly good increase in DRB1 *10 (2.16%; OR: 2.16 CI; 0.96 – 4.84).

Conclusions

The low sensitivity of RF (41%) in RA in this rural COPCORD is consistent with many other population surveys reported from different parts of the world. The high specificity of RF in the current study is rather reassuring. These results suggest an increase in shared epitope bearing alleles in hospital based RA cases as compared with community based RA. The hypothesis that HLA-DR is associated with severity and not susceptibility in RA is evident from these data. However, the community data probably best reflects the ground reality.

Key Indexing Terms

Antinuclear Antibodies; Immunoenzyme Method, Filter Paper Blood Sample, Systemic Lupus Erythematosus, Sero-epidemiology.