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Objectives To explore associations between traditional inflammatory markers (the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and clinical manifestations, specific autoantibodies, disease activity, and clinically required glucocorticoid (GC) therapy in patients with systemic lupus erythematosus (SLE).Methods The study included 436 SLE patients (87.6% women, median age 37 [26–49] years; disease onset at 28 [20–40] years). The median SLEDAI-2K activity index was 10 (6–16), and SLICC/ACR damage index 1 (0–2). At baseline, 60% received oral GC (median dose 10 [10–15] mg/day of prednisolone equivalent), 55% aminoquinoline drugs, and 10% other immunosuppressants. In all patients, the involvement of various organs and systems was evaluated, and laboratory assessments included ESR (Westergren method), CRP (latex turbidimetric method), and specific autoantibody profiles determined by ELISA. Statistical analysis used the Wilcoxon–Mann–Whitney test, Spearman’s correlation, and ROC analysis.Results About half of the patients with SLE had elevated ESR (52.4%) and CRP (51.5%) levels, which showed a moderate correlation with each other (r = 0.31, p < 0.01). CRP correlated with age (r=0.21, p<0.01) and was higher in patients with serosal or mucosal involvement, Sjögren’s syndrome, anemia, and irreversible organ damage (all p<0.05), but did not correlate with disease activity. ESR correlated with SLEDAI-2K (r=0.17, p<0.01) and was higher in patients with renal, cardiac, pulmonary, and mononuclear phagocyte system involvement, arthritis, fever, and anti-Ro/SSA antibodies (p<0.05). Discordance between ESR and CRP (high ESR/low CRP) was associated with nearly a threefold higher frequency of central nervous system involvement (31% vs 11%, p=0.04). Treatment-naïve patients showed significantly higher ESR and CRP than those receiving GC and/or immunosuppressants (p<0.01). ESR with a cut-off 42 mm/h (sensitivity 48%, specificity 94%) and CRP with a cut-off 27.6 mg/L (sensitivity 38%, specificity 95%) predicted the use of high-dose GC (>30 mg/day prednisolone equivalent).Conclusions ESR and CRP demonstrate distinct clinical associations in SLE and should not be considered interchangeable. Their concurrent evaluation provides a more comprehensive assessment of inflammatory activity and may help guide individualized treatment strategies.