Implementation of Anti-Bip Antibodies as A Novel Biomarker in The Diagnosis of Rheumatoid Arthritis

Abstract

Background: Anti-BiP antibodies, directed against the binding immunoglobulin protein (BiP), have recently been identified as potential biomarkers in autoimmune diseases such as rheumatoid arthritis (RA). They are involved in ER stress responses and immune dysregulation, pathogenic forces contributing to RA. Methods: In this matched case–control study, 75 established RA cases along with 45 age and sex matched controls attended Al-Hakeem General Hospital, Al-Najaf, Iraq from March 2024 through February 2025. The diagnosis was established according to the 2010 ACR/EULAR classification criteria for RA. Detection of Anti-BiP antibodies in serum was carried out using standardized ELISA method and also serum levels of inflammatory markers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]) were estimated. Results: The average serum Anti-BiP antibody level was higher in patients with RA (38.7 ± 8.5 U/mL) than in controls (15.2 ± 5.6 U/mL; p < 0.001). There was also a strong positive correlation between Anti-BiP antibodies and CRP levels (r = 0.68, p < 0.001) as well ESRs (r = 0.62, p < 0.001). The ROC curve analysis showed good diagnostic accuracy for the Anti-BiP antibodies (AUC = 0.902, p < 0.001). At the cut-off level of ≥22.3 U/mL, sensitivity and specificity for diagnosis of RA were 72% and 81.5% respectively. Conclusion: Serum Anti-BiP antibody are significantly increased in patients with RA and they are closely associated with inflammation activity. Their high positive diagnostic accuracy demarcates Anti-BiP autoantibodies as a promising new solid-state reliable biomarker for the early diagnosis and clinical estimation of rheumatoid arthritis.

Keywords:

Rheumatoid arthritis, Anti-Bip, CRP, ESR, Sensitivity, Specificity

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