Occurrence of anti-CCP2 and RF isotypes and their relation to age and disease severity among Sudanese patients with rheumatoid arthritis

Abstract

Objective Anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2) and rheumatoid factor (RF) in rheumatoid arthritis (RA) has been extensively assessed in industrialized countries. We investigated the diagnostic and prognostic impact of anti-CCP2 and RF isotypes in a Sudanese cross-sectional RA cohort. Methods Consecutive RA patients (n = 281) diagnosed according to the 1987 ACR criteria were included 2008-2010. Anti-CCP2 and RF isotypes (IgA, IgM, and IgG) were measured by enzyme immunoassay in 262 patients, with reference intervals aligned to the same diagnostic specificity as for anti-CCP2 (97.6%) using national controls. Results IgA RF was the predominant RA-associated autoantibody (56%), followed by IgM RF and anti-CCP2 (both 52%) and IgG RF (49%). In receiver operator characteristic analysis, IgA RF also showed the largest area under the curve. Patients with IgG RF were younger and had 8 years lower median age of disease onset compared to antibody negative patients (p < 0.0001). IgG RF was the only marker associated with a high number of involved joints (p = 0.028), and together with anti-CCP2 were the strongest markers for finger deformities (p = 0.016 and p = 0.012), respectively. No statistical differences were found for disease duration, ESR and Hb levels, and occurrence of erosions/osteopenia for any of the investigated autoantibodies. Conclusion Whereas IgA RF showed the best diagnostic performance, IgG RF associated with low age of RA onset, high number of involved joints, and finger deformities. These findings indicate that RA-associated antibodies other than conventional IgM RF and anti-CCP2 might be informative in non-Caucasian RA populations.

Elevated IgA antiphospholipid antibodies in healthy pregnant women in Sudan but not Sweden, without corresponding increase in IgA anti-β2 glycoprotein I domain 1 antibodies

“… 10 , 16 – 19 In parallel, our group recently reported a predominance of IgA RF in Sudanese rheumatoid arthritis patients. 45 In the current study, the high levels and prevalence of IgA anti-CL and anti-β 2 GPI in Sudanese pregnant females was not associated with increased IgA RF levels, arguing against a general IgA increase in these women but instead indicating an antigen-specific increase in IgA aPL. Interestingly, when comparing Swedish pregnant with non-pregnant women as well as serially investigating anti-CL and anti-β 2 GPI autoantibodies throughout Swedish normal pregnancies we could not observe increase in any aPL, including the IgA isotype.…”

Analysis of Serum Immune Markers in Seropositive and Seronegative Rheumatoid Arthritis Among Sudanese Patients and the Relation Between the Serotype and Joint Involvement: A Cohort Study

“…The overall ESR median value was found to be 35 ± 28.9 SD, this was inconsistent with the median of other studies 18 which was 56 mm/h; this gives an idea about the trend of ESR among the studied patients. Still, the difference could be attributed to the sample size.…”

Rheumatoid arthritis autoantibodies and their association with age and sex

“…Although IgM RF is the most common RF isotype among RA patients of Caucasian ancestry, other RF isotypes appear to be more relevant in other geographical regions. In Asian populations, IgG RF is dominating, or as common as IgM (reviewed in ( 6)), whereas IgA RF showed the highest sensitivity in a cross-sectional RA cohort from Khartoum, Sudan (7). The 1987 ACR classification criteria state that RF should be measured "by any method for which the result has been positive in <5% of normal control subjects", and no upper limit of specificity is set (1).…”

“…Therefore, future studies evaluating the impact of individual autoantibodies in RA should adjust for or otherwise accommodate age and sex. Such adjustments might be even more important in the future due to migration, as different autoantibody isotypes predominate among RA patients of different ethnicities(6,7).…”