FADD Protein for the Early Diagnosis of Rheumatoid Arthritis

FADD (Fas-Associated Death Domain) protein in patients' serum and synovial fluid could be a biomarker of inflammation in rheumatic diseases. We tested whether the baseline serum FADD level would be a predictive factor for meeting the American College of Rheumatology (ACR)/EULAR 2010 criteria for rheumatoid arthritis (RA) in order to facilitate the early diagnosis of RA.

We measured FADD by enzyme-linked immunosorbent assay in the sera from 659 patients with early arthritis from the Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort (at least two swollen joints for more than six weeks and less than six months, no previous exposure to glucocorticoids or disease-modifying antirheumatic drugs). Patients were eligible for inclusion in the cohort if they had a definitive or probable clinical diagnosis of RA or a diagnosis of undifferentiated arthritis (UA) with a potential for progressing to RA, according to the 2010 ACR/EULAR criteria for RA.

At inclusion, serum FADD protein was detected in 501 of 659 (76%) patients (range 0-1,503 ng/mL) and levels were independent of patient age and sex. Statistically significant higher levels of FADD were detected in the serum from patients with diagnosed RA at inclusion or who were diagnosed with RA thereafter, than from patients with UA. Receiver operating characteristic curve analysis indicated that a FADD >8 ng/mL had the best sensitivity (50.95%) and specificity (85.71%) for the diagnosis of RA. Moreover, FADD levels were positively associated with anti-citrullinated protein antibody (ACPA), rheumatoid factors, proinflammatory interleukin-1β (IL-1β), IL-6 and IL-2, and APRIL, a marker of B lymphocyte activation.

Baseline serum FADD level measurement appeared as a helpful biomarker for the early diagnosis of RA, particularly in patients who were ACPA negative.