Presence of autoantibodies to the glycolytic enzyme alpha-enolase in sera from patients with early rheumatoid arthritis.
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 alpha-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 alpha-enolase in protein maps, only 8 recognized the recombinant (unmodified) alpha-enolase. The specificity of anti-alpha -enolase antibodies for RA was 97.1%. Half of the anti-alpha -enolase-positive RA patients were negative for both rheumatoid factor and antifilaggrin antibodies. The presence of anti-alpha-enolase antibodies was the greatest predictive factor of radiologic progression in the first 66 RA patients included.


CONCLUSIONS
Autoantibodies to alpha-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.
Saulot
Vincent
V
Institut National de la Santé et de la Recherche Médicale, Rouen, France.
Vittecoq
Olivier
O
Charlionet
Roland
R
Fardellone
Patrice
P
Lange
Catherine
C
Marvin
Laure
L
Machour
Nadine
N
Le Loët
Xavier
X
Gilbert
Danièle
D
Tron
François
F
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D006019:Glycolysis; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000276:immunology; D010751:Phosphopyruvate Hydratase / Q000032:analysis / Q000276:immunology*; D011237:Predictive Value of Tests; D011379:Prognosis; D011994:Recombinant Proteins / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D001323:Autoantibodies; D011994:Recombinant Proteins; D010751:Phosphopyruvate Hydratase