Background and objectives
Autoantibodies to deiminated proteins are known to be the most specific serological marker for the diagnosis of rheumatoid arthritis (RA). We recently showed that deiminated fibrin is the major target of this family of autoantibodies in rheumatoid synovial tissue. We subsequently developed, and validated on a large series of patients with established rheumatic diseases, an ELISA for the detection of circulating autoantibodies to deiminated human fibrinogen (AhFibA). The test was shown to be the most efficient (specific and sensitive) serological criterion for the diagnosis of RA.
We collected 352 sera from patients with arthritides of recent onset (disease duration <1 year). The diagnosis was established after at least 2 years' follow-up. The patients were then classified into two groups, 175 with RA and 177 with non-RA inflammatory rheumatic diseases. The previously developed ELISA, using in vitro deiminated human fibrinogen as immunosorbent, was used for detection and titration of AhFibA. Antibodies to cyclic citrullinated peptide (CCP) were sought in accordance with the manufacturer's procedure (Immunoscan RA, Euro-diagnostica). Rheumatoid factor (RF) was titrated by nephelometry (RF-reagent for Image, Beckman Coulter).
The diagnostic sensitivity of AhFibA was found to be significantly higher than those of CCP (P < 0.05) and RF (P < 0.001) (Table 1). The positive predictive values (PPV) of the three tests were all found to be very high and were not significantly different. The negative predictive values (NPV) were too low to be diagnostically useful. Among the AhFibA-positive RA sera 83% were RF-positive, while among the AhFibA-negative, only 13% were RF-positive.
Table 1. Diagnostic indices computed at thresholds allowing 0.985 specificity to be reached
Unlike the case with RF, autoantibodies to deiminated proteins are confirmed to be of diagnostic value in early arthritides. The detection of these autoantibodies by ELISA using their synovial target (deiminated fibrin) appears the most efficient method for the diagnosis of early RA.