CBC‑derived inflammatory indices for rheumatoid arthritis diagnosis and activity assessment: differential performance by serostatus

Background Rheumatoid arthritis (RA) is an autoimmune disease for which better biomarkers are needed, especially in seronegative cases. This study evaluates complete blood count (CBC)-derived inflammatory indices – neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) – for RA diagnosis and disease activity assessment, with comparisons between seropositive and seronegative RA. Methods We conducted a retrospective case–control study of 230 RA patients and 115 age- and sex-matched healthy controls. CBC-derived indices were calculated from routine blood counts. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curves (area under the curve, AUC) for RA versus controls overall and stratified by serostatus. Associations with disease activity (DAS28-CRP, SDAI, CDAI) were assessed via correlations and ROC analysis for active (moderate/high) versus inactive (remission/low) RA. Results All five indices were significantly elevated in RA patients compared to controls (all P < 0.001). MLR showed the highest diagnostic accuracy (AUC = 0.771), followed by SIRI (0.72) and PLR (0.70); NLR and SII were more modest (≈0.69–0.68). In seronegative RA, diagnostic discrimination declined (best AUC = 0.707 for MLR; SII and SIRI AUCs ~0.56–0.59). NLR, SII, and SIRI correlated moderately with CRP, ESR, and composite scores (Spearman ρ ~0.3–0.4, P < 0.001), and were higher in active RA (DAS28-CRP AUCs 0.668–0.700). SII and SIRI provided the top discrimination of active disease (AUC ~0.70). PLR showed minimal correlation with activity and no significant difference between active and inactive RA. Conclusion CBC-derived inflammatory indices are elevated in RA and reflect systemic inflammation. MLR is the most robust index for distinguishing RA from healthy individuals, while SII, SIRI, and NLR are useful for gauging disease activity. In seronegative RA, diagnostic performance was attenuated overall, with MLR retaining fair discrimination while SII/SIRI/NLR showed limited utility.