Anticyclic citrullinated peptide antibodies, antikeratin antibodies and igm-rf as diagnostic markers for rheumatoid arthritis

الملخص EN

Background : Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease, but specific and practicable tests for its diagnosis are lacking.

Objective : to evaluate the diagnostic performance of anticyclic citrullinated peptide antibodies (anti-CCP), ant keratin antibodies (AKA) and IgM rheumatoid factor (IgM-RF) in active rheumatoid arthritis patients.

We also aimed to clarify the value of those markers in the discrimination between RA and other connective tissue diseases and to assess their relevance of to the clinical severity of the disease.

Study design : this study was conducted on 132 subjects including 60 patients with active rheumatoid arthritis (patients group) ; 42 patients with other connective tissue diseases (patients control) and 30 age and sex matched apparently healthy subjects (healthy control).

RA patients were sub classified into 44 patients without extra-articular manifestations (subgroup I) and 16 patients with extra-articular manifestations (subgroup II).

The latter group included 8 patients with carpal tunnel syndrome, 4 with right-sided pleural effusion, 2 with episcleritis and 2 with pericarditis.

All subjects included in the study underwent an assay of IgM-RF, anti-CCP (with ELISA technique) and AKA with the indirect immunofluorescence technique.

Results : there was marked elevation of IgM-RF (90.2 ± 91.3 U), anti-CCP (98.9 ± 66.4 U) and the number of AKA positive cases (56.6 %) in the whole RA patients group.

As for RA \ subgroups, the values were 85.7 ± 85.8 U, 93.1 ± 65.5 U and 54.5 %, respectively in subgroup I and 102.6 ± 106.9 U, 154.8 ± 68.3 U and 62 %, respectively in subgroup II.

This was in comparison to healthy controls whose values were 8.0 ± 5.2 U, 21.9 ± 11.5 U and 10%, respectively (p < 0.001) as well patients control whose values were 8.8 ± 3.9 U, 27.7 ± 11.4 U and 11.9 %, respectively (p < 0.001).

Moreover, anti-CCP levels were significantly higher in subgroup II than subgroup I (p < 0.05).

A highly significant correlation was found between IgM-RF and anti-CCP (rs = 0.75, p<0.001).

Furthermore, IgM-RF and anti-CCP correlated significantly with the disease activity score (DAS) (rs= 0.68 & 0.83, respectively), duration of disease (rs = 0.61 & 0.75, respectively), CRP (rs= 0.81 & 0.79, respectively) and ESR (rs = 0.85 & 0.78, respectively) p < 0.001.

Stepwise multiregression analysis revealed that in RA patients without extra-articular manifestations, the best predictor of disease activity was anti-CCP, IgM-RF and CRP (partial r = 0.68, 0.60 & 0.55, respectively) with anti-CCP being the most indicative parameter (F = 17 p < 0.01).

On the other hand, the best markers FOR RA with extra-articular manifestations were IgM-RF and ESR (partial r=0.59 & 0.42, respectively) with IgM-RF being the most indicative parameter (F = 12 p < 0.01).

The study of diagnostic performance of IgM-RF, anti-CCP in RA patients versus patients control revealed that the highest diagnostic sensitivity was for IgM-RF (83.3 %) followed by anti-CCP (80 %) then AKA (56.7%), while the highest diagnostic specificity was for anti-CCP (95.2%) then IgM-RF (90.5%) and lastly AKA (88.1%).

Combined use of both IgM-RF and anti-CCP in multi-ROC curve revealed improvement in diagnostic sensitivity (96.7 %) and specificity (100 %) Conclusion : Anti-CCP proved its superior specificity in establishing the diagnosis of RA.

Its assay concomitantly with IgM-RF offers excellent diagnostic sensitivity and specificity.

Thus, it could help in diagnosis and differential diagnosis of RA from other connective tissue diseases.

Anti-CCP is the best indicator of disease activity in patients without extra-articular manifestations.

For patients with extra-articular manifestations, the best indicator of disease activity was IgM-RF.