A Comparative Analysis of Inflammatory Markers and Disease Activity Score between Seropositive and Seronegative Rheumatoid Arthritis





Seropositive RA, seronegative RA, C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR), Disease activity score-28 (DAS-28)


Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is characterized by persistent inflammation in the joints and other tissues, leading to significant joint damage irrespective of the serogroups i.e. seropositive and seronegative RA. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are commonly used biomarkers to monitor inflammation in RA and to inform therapeutic decision-making. Methods: The present study aimed to investigate the relationship between CRP and ESR levels and the severity of disease among seronegative and seropositive patients. ACR/EULAR 2010 criteria were used to recruit RA patients in the study. Clinical assessments were performed to estimate the RF, ACCP antibodies, ESR and CRP. Swollen and tender joints were also taken into account for the calculation of disease activity score-28. Results: The results indicated that significantly elevated CRP levels were consistently observed in seropositive RA, in conjunction with seronegative RA patients (p=0.036). ESR levels were found elevated between the two groups but were not found to be statistically different (p=0.885). DAS28-CRP and DAS28-ESR results showed high severity of disease (>5.1) in both seronegative and seronegative RA patients. Conclusion: The findings of this study highlight the diagnostic and prognostic significance of ESR and CRP levels in RA among seronegative and seropositive patients, particularly in differentiating seropositive and seronegative cases and in guiding therapeutic decisions.


Malmström V, Catrina AI, Klareskog L. Author correction: The immunopathogenesis of seropositive rheumatoid arthritis: From triggering to targeting. Nat Rev Immunol 2022; 22(7): 459.

Wu CY, Yang HY, Luo SF, Lai JH. From rheumatoid factor to anti-citrullinated protein antibodies and anti-carbamylated protein antibodies for diagnosis and prognosis prediction in patients with rheumatoid arthritis. Int J Mol Sci 2021; 22(2): 686.

Farid SS, Azizi G, Mirshafiey A. Anti-citrullinated protein antibodies and their clinical utility in rheumatoid arthritis. Int J Rheum Dis 2013; 16(4): 379-86.

Selmi C, Gershwin ME. Diagnosis and classification of reactive arthritis. Autoimmun Rev 2014; 13(5): 546-9.

Scherer HU, Häupl T, Burmester GR. The etiology of rheumatoid arthritis. J. Autoimmun 2020; 110: 102400.

Alam J, Jantan I, Bukhari S. Rheumatoid arthritis: Recent advances on its etiology, role of cytokines and pharmacotherapy. Biomed Pharmacother 2017; 92: 615-33.

Darrah E, Andrade F. Rheumatoid arthritis and citrullination. Curr Opin Rheumatol 2018; 30(1): 72-8.

De Rycke L. Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: Diagnostic value, associations with radiological progression rate, and extra-articular manifestations. Ann Rheum Dis 2004; 63(12): 1587-93.

Vallbracht I, Helmke K. Additional diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis. Autoimmun Rev 2005; 4(6): 389-94.

Cush JJ. Rheumatoid arthritis. Rheum Dis Clin 2022; 48(2): 537-47.

Litao MK, Kamat D. Erythrocyte sedimentation rate and C-reactive protein: How best to use them in clinical practice. Pediatr Ann 2014; 43(10): 417-20.

Pope JE, & Choy EH. C-reactive protein and implications in rheumatoid arthritis and associated comorbidities. Semin Arthritis Rheum 2021; 51(1): 219-29.

Listing J, Kekow J, Manger B, et al. Mortality in rheumatoid arthritis: The impact of disease activity, treatment with glucocorticoids, TNFΑ inhibitors and Rituximab. Ann Rheum Dis 2013; 74(2): 415-21.

Prevoo ML, Van'T Hof, MA, Kuper HH, et al. Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38(1): 44-8.

Fransen J, van Riel PLC. M. The disease activity score and the eular response criteria. Rheum Dis Clin 2009; 35(4): 745-57.

Singh JA, Saag KG, Bridges SL, et al. American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2015; 68(1): 1-26.

Orr CK, Najm A, Young F, McGarry T, Biniecka M, Fearon U, Veale DJ. The utility and limitations of CRP, ESR and DAS28-CRP in appraising disease activity in rheumatoid arthritis. Frontiers in medicine 2018; 5: 185.

Aletaha D, Neogi T, Silman AJ. et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010; 62: 2569-81.

Salma K, Nessrine A, Krystel E, Khaoula EK, Noura N, Khadija E, Taoufik H. Rheumatoid arthritis: seropositivity versus seronegativity; A comparative cross-sectional study arising from moroccan context. Curr Rheumatol Rev 2020; 16(2): 143-8.

Choi ST, Lee KH. Clinical management of seronegative and seropositive rheumatoid arthritis: a comparative study. PLoS One 2018 Apr 6; 13(4): e0195550.

Ortona E, Pierdominici M, Maselli A, Veroni C, Aloisi F, Shoenfeld Y. Sex-based differences in autoimmune diseases. Annali dell'Istituto superiore di sanita 2016; 52(2): 205-12.

Turkcapar N, Demir O, Atli T, et al. Late onset rheumatoid arthritis: clinical and laboratory comparisons with younger onset patients. Arch Gerontol Geriatr 2006; 42: 225e31.

Cylwik, B., Chrostek, L., Gindzienska-Sieskiewicz, E., Sierakowski, S., & Szmitkowski, M. Relationship between serum acute-phase proteins and high disease activity in patients with rheumatoid arthritis. Adv Med Sci 2010; 55(1): 80-5.

Derksen VF, Huizinga TW, van der Woude D. The role of autoantibodies in the pathophysiology of rheumatoid arthritis. Semin Immunopathol 2017; 39(4): 437-46.

Kim KW, Kim BM, Moon HW, Lee SH, Kim HR. Role of C-reactive protein in osteoclastogenesis in rheumatoid arthritis. Arthritis Res Ther 2015; 17: 1-2.

Grassi W, De Angelis R, Lamanna G, Cervini C. The clinical features of rheumatoid arthritis. Eur J Radiol 1998; 27: 18-24.

Juan Camilo Sánchez-Flórez, Daniela Seija-Butnaru, Edmundo Gónima Valero, Claudia del Pilar Acosta Acosta, Sebastian Amaya. Pain management strategies in rheumatoid arthritis: A Narrative Review, J. Pain Palliat. Care Pharmacother 2021; 35(4): 291-9.

Lillian Barra, Janet E. Pope, et al. Prognosis of seronegative patients in a large prospective cohort of patients with early inflammatory arthritis and the CATCH Investigators, J Rheumatol 2014; 41(12): 2361-9

Coffey CM, Crowson CS, Myasoedova E, Matteson EL, Davis III JM. Evidence of diagnostic and treatment delay in seronegative rheumatoid arthritis: missing the window of opportunity. Mayo Clin Proc 2019; 94(11): 2241-8.




How to Cite

Amber Khan, Ume Kulsoom, Maham Ghouri, Sehrish Fatima, Saima Saleem, & Sitwat Zehra. (2023). A Comparative Analysis of Inflammatory Markers and Disease Activity Score between Seropositive and Seronegative Rheumatoid Arthritis. BioSight, 4(4), 1–8. https://doi.org/10.46568/bios.v4i4.133



Original Article