Presence of autoantibodies to the glycolytic enzyme α‐enolase in sera from patients with early rheumatoid arthritis

Abstract

Objective. To identify a new autoantigen/ autoantibody population in rheumatoid arthritis (RA) sera.Methods. Following a population-based recruitment effort, 255 patients with very early arthritis (median disease duration 4 months) were studied using different clinical, biologic, and radiologic assessments. After a followup period of 1 year, patients were classified as having RA (n ‫؍‬ 145), non-RA rheumatic diseases (n ‫؍‬ 70), and undifferentiated arthritis (n ‫؍‬ 40). Patients' sera were analyzed by one-dimensional (1D) and 2D Western blotting. The recognized 50-kd protein was analyzed by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry (MS). RA serum reactivities were evaluated against the recombinant protein synthesized by an in vitro coupled transcription-translation system.Results. On 1D Western blots, 36 of the 145 RA sera bound to a 50-kd polypeptide. On 2D Western blots, anti-50-kd؉ RA sera recognized a triplet of isoelectric point 6.5-7.0 and a molecular mass of 50 kd. The 3 spots of the triplet were analyzed by MALDI-TOF MS and were shown to correspond to human ␣-enolase. A goat anti-enolase antiserum, which recognized a band comigrating with the 50-kd antigen on 1D Western blots, gave a labeling pattern on 2D Western blots similar to that observed with anti-50-kd؉ RA sera. Among the 36 RA sera that identified ␣-enolase in protein maps, only 8 recognized the recombinant (unmodified) ␣-enolase. The specificity of anti-␣-enolase antibodies for RA was 97.1%. Half of the anti-␣-enolase-positive RA patients were negative for both rheumatoid factor and antifilaggrin antibodies. The presence of anti-␣-enolase antibodies was the greatest predictive factor of radiologic progression in the first 66 RA patients included.Conclusion. Autoantibodies to ␣-enolase, an enzyme of the glycolytic pathway, are present in the sera of patients with very early RA and have potential diagnostic and prognostic value for RA.

Anti-Alpha-Enolase Antibody as a Serologic Marker and Its Correlation with Disease Severity in Intestinal Behçet’s Disease

“…This protein is also found on the surface of streptococci, which can cause acute rheumatic fever 3 Cumulative rate of steroid use for the IgM anti-a-enolase antibody positive and negative groups were 38 and 31% at 1 year, 40 and 35% at 2 years, 46 and 43% at 3 years, 51 and 48% at 4 years, and 60 and 48% at 5 years, respectively (P = 0.022) [21], and has been identified as a type of heat-shock protein [22]. The evidence suggests that a-enolase plays an important role in autoimmune and inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, discoid lupus erythematosus, cancer-associated retinopathy, ANCA-positive vasculitis, systemic sclerosis, endometriosis, primary membranous nephropathy, autoimmune liver disease, and mixed connective tissue disease [20,23,24]. In our study, IgM AAEA was positive in 54 of 80 (67.5%) intestinal BD patients, which was higher than the prevalence among BD patients (45.0%) reported by Lee et al [13].…”

Consenso da Sociedade Brasileira de Reumatologia 2011 para o diagnóstico e avaliação inicial da artrite reumatoide

“…The objective is to develop methods with sensitivity and specifi city for earlier RA diagnosis, more reliable activity markers, and prognostic indicators. Some of the autoantibodies used in RA investigation are as follows: mutated citrullinated vimentin antibodies (anti-MCV); [49][50][51] antikeratin antibodies (AKA); anti-perinuclear factor (APF); 52 antifi laggrin autoantibodies; 53 anti-human citrullinated fi brinogen antibodies (ACF); 54 anti-heterogeneous nuclear ribonucleoprotein A2 autoantibody (anti-RA33); 52 anti-interleukin 1 antibody (anti-IL1); 55 anti-alpha-enolase antibody; 56 and anti-advanced glycation end-products antibody. 57 These antibodies have, in general, good specifi city, but sensitivity lower than that of anti-CCP for diagnosing RA.…”

Proteomic Surveillance of Autoantigens in Relapsing Polychondritis

“…The third identified protein was alpha-enolase. Similarly as for vimentin, autoantibodies to alpha-enolase have also been reported in various autoimmune diseases (18,30,32). Thereby, the autoantibodies to alpha-enolase may be a general phenomenon to systemic autoimmune disease.…”