Prevalence and clinical value of IgA and hidden rheumatoid factors in juvenile rheumatoid arthritis

Abstract

Background: Juvenile rheumatoid arthritis (JRA) is so difficult to be diagnosed early and a small subgroup of patients has positive IgM rheumatoid factor (RF) detected by the standard agglutination techniques.
Objective: To investigate the prevalence of IgA and hidden RFs among patients with JRA, to evaluate their diagnostic value in comparison to classic RF and to outline their relation to disease activity, severity as well as to therapy.
Methods: The study included 46 patients with JRA (31 females and 15 males). Thirty patients had polyarticular JRA, 9 had oligoarticular JRA and 7 had systemic-onset JRA. Twelve patients had active disease. Thirteen systemic lupus erythematosus patients and 32 healthy subjects were studied as controls. Evaluation was carried out clinically and radiologically (using modified Larsen scoring). Laboratory investigations included CBC, ESR, classic IgM RF (latex agglutination), ANA (indirect  immunofluorescence), IgA-RF (ELISA) and hidden RF seropositivity (ion exchange chromatography).
Results: All JRA patients had significantly higher IgA-RF (121.5 ± 195.4 mg/dL) and positivity of hidden RF (56.5%) than lupus (14 ± 6.6 mg/dL and 7.7% respectively) and healthy controls (13.7 ± 6.2 mg/dL and 0% respectively). Classic IgM RF had only 10.9% sensitivity in diagnosing JRA. IgA and hidden RFs had higher sensitivities (50% and 56.5% respectively). Specificity, positive and negative predictive values of IgA-RF were 97.7%, 95.8% and 65.7% and for hidden RF, they were 95.5%, 92.9% and 68.3%. Interestingly, combined positivity of IgA and hidden RFs had 100% specificity and positive predictive value for JRA. Classic RF did not correlate with disease activity and severity in terms of ESR, activity score and Larsen Index. In contrast, patients with active disease had significantly higher value of IgA-RF and positivity of hidden RF than those with quiescent disease. Also, IgA-RF had significant positive correlation with ESR, activity score and Larsen index. Similarly, patients with positive hidden RF had significantly higher values of ESR, activity score and Larsen index than those with negative hidden RF. Steroid therapy was associated with significantly higher level of IgA-RF and positivity of hidden RF, perhaps related to disease severity.
Conclusion: IgA and hidden RFs are more sensitive tests in diagnosing JRA than classic IgM RF. Also, the combined positivity of IgA and hidden RFs can confirm the diagnosis of JRA in doubtful cases. The fact that IgA and hidden RFs gave positive results in the meantime that classic RF was negative, together with their significant relation to disease activity and severity highlights their clinical value as reliable laboratory markers of JRA.

Key words: juvenile rheumatoid arthritis, rheumatoid factors, IgA-RF, hidden RF, SLE.