Anti cyclic citrullinated peptide antibodies in IgM rheumatoid factor positive patients: a new insight

ABSTRACT

The presence of IgM rheumatoid factor [IgM RF] is one of the clinical criteria for the diagnosis of rheumatoid arthritis [RA]. The cutoff point of IgM RF assays is usually based on a reference level obtained from normal subjects in the same population as the patients. However, raising the cutoff values increases the specificity of RF testing. The present study was undertaken to investigate this observation with the help of anti cyclic citrullinated peptide [CCP] antibodies to be of potential diagnostic value. Seventy six patients were chosen with arthritis and IgM RF titers > 20 units/ml. Subsequently, patients were classified according to their IgM RF titers patients with titers patients with iters >40 units/ml [group B] and patients [selected from group B] with titers >120 units/ml [group C]. Twenty one RA patients with IgM RF negative and positive anti CCP antibodies were also included in this study. In all serum samples, IgM RF, anti CCP, hepatitis C virus antibodies [HCV], anti-Smith and anti-ribonucleoprotein [anti-RNP] antibodies were determined by ELISA. PCR analysis was performed for all patients with positive HCV antibodies. Antinuclear antibodies [ANA] and anti-dsDNA were determined by indirect immunofluorescence. In patients of groups A, B and C, RA was detected in 28.6, 80.5 and 83.3% of all patients, respectively. Anti CCP antibodies detected RA in 22.85, 75.6 and 77.8% of all patients in groups A, B and C, respectively. IgM RF positive non RA patients were diagnosed in 71.4, 19.5 and 16.7% among all patients included in group A, B and C, respectively. In group A, anti CCP antibodies correctly classified 24/25 [96%] of patients with false positive IgM RF as non RA patients, they were positive in only one patient with rhupus. Anti CCP antibodies were positive in 2.8, 4.9 and 11.1% in non RA patients among all patients in group A, B and C, respectively. Anti CCP antibodies were present in 80, 93.9 and 93.3% of RA patients in groups A, B and C, respectively. The overall presence of anti CCP in seropositive RA patients was 90.6%. Kappa statistics showed an excellent agreement between IgM RF and anti CCP for the serodiagnosis of RA. Among the non RA patients of group A, it was found that 9/25 [36%] of patients diagnosed as having HCV infection. Anti CCP antibodies were negative in all HCV patients. Low positive titers of anti CCP antibodies were more prevalent [76.2%] in patients with seronegative RA than in patients with seropositive RA [17.9%]. Results demonstrated that [1] anti CCP antibodies correctly classified about 24/25 [96%] of patients with false positive IgM RF [< 40 units/ml] as non RA, [2] high titers of IgM RF [>120 units/ml] are of similar high specificity to anti CCP antibodies and [3] anti CCP antibodies are able to differentiate between patients with HCV infection associated with arthritis and patients with RA