J Rheum Dis.  2022 Jul;29(3):171-180. 10.4078/jrd.2022.29.3.171.

Clinical Implications of Shared Epitope and Anti-citrullinated Peptide Antibody in Patients With Rheumatoid Arthritis

• Jung SM
• Park YJ
• Park KS
• Kim KJ

• KMID: 2530681
• DOI: http://doi.org/10.4078/jrd.2022.29.3.171

Abstract

Objective
The shared epitope (SE) and anti-citrullinated peptide antibody (ACPA) are involved in the pathogenesis of rheumatoid arthritis (RA). This study evaluated the clinical implications of SE and ACPA in terms of disease manifestation and response to biologic disease modifying anti-rheumatic drugs (DMARDs).
Methods
Patients with identified human leukocyte antigen (HLA)-DRB1 alleles were included to compare the clinical characteristics and drug survival rate of tumor necrosis factor (TNF) inhibitors or abatacept based on the presence of SE and ACPA.
Results
Of the 533 patients with identified HLA-DRB1 alleles, 329 patients (61.7%) with SE alleles showed higher disease activity and erosive changes compared to patients without SE alleles. SE-positive patients were more likely to start biologic (b-) or targeted synthetic DMARDs (tsDMARDs) within the first 5 years (p=0.020). The presence of SE, smoking, dyslipidemia, and higher erythrocyte sedimentation rate were independently associated with the initiation of b- or tsDMARDs (p=0.016, 0.028, 0.031, and 0.001, respectively). The presence of SE and ACPA did not affect the drug survival rate of TNF inhibitors, whereas the abatacept retention rate was higher in ACPA-positive patients (p=0.024).
Conclusion
The presence of SE affected disease characteristics and prognosis in Korean patients with RA without a significant impact on drug survival rate of TNF inhibitors and abatacept. ACPA positivity was associated with abatacept drug retention, suggesting that abatacept may be helpful in ACPA-positive patients than in ACPA-negative patients.

Keyword

Rheumatoid arthritis; Epitopes; Antibodies; Abatacept

Figure

• 

  Fig. 1 (A) ACPA positivity and the three ACPA subgroups with respect to SE status. ACPA was divided into three categories: <5 U/mL (negative), 5~200 U/mL (low to moderate level), and >200 U/mL (high level). (B) ACPA positivity for different combination of smoking and SE status. Categorical comparison between the two groups was verified using the Chi-squared test. The number (percentage) is marked in the middle of each bar. ACPA: anti-cyclic citrullinated protein antibody, SE: shared epitope.

• 

  Fig. 2 (A) Proportion of b- or ts-DMARDs use with respect to the SE status. The number (percentage) is marked in the middle of each bar. (B) Cumulative incidence of the initiation of b- or ts-DMARDs based on the SE status over 5 years. (C) Forest plots showing hazard ratios of b- or tsDMARD initiation in patients with RA. The Cox proportional hazards model was used to estimate hazard ratios and associated 95% confidence intervals. ACPA: anti-citrullinated protein antibody, bDMARDs: biologic disease-modifying anti-rheumatic drugs, BMI: body mass index, cDMARDs: conventional disease-modifying anti-rheumatic drugs, CRP: C-reactive protein, DM: diabetes mellitus, ESR: erythrocyte sedimentation rate, HBP: hypertension, HR: hazard ratio, RF: rheumatoid factor, SE: shared epitope, SHS: van der Heijde modified Sharp score, tsDMARDs: targeted synthetic disease-modifying anti-rheumatic drugs. *p<0.05, **p<0.01.

• 

  Fig. 3 The drug survival rate of TNF inhibitors and abatacept over 24 months by Kaplan–Meier estimates. (A) Plot with respect to SE status. (B) Plot with respect to ACPA status. ABTC: abatacept, ACPA: anti-citrullinated protein antibody, SE: shared epitope, TNFi: tumor necrosis factor inhibitors, HR: hazard ratio, CI: confidence interval.

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