Autoantibodies recognizing citrullinated rat filaggrin in an ELISA using citrullinated and non-citrullinated recombinant proteins as antigens are highly diagnostic for rheumatoid arthritis

Abstract

SUMMARYThe objective of the study was to determine the diagnostic value for rheumatoid arthritis (RA) of antifilaggrin autoantibodies (autoAb) recognizing citrullinated recombinant rat filaggrin (ACRF) in community cases of very early arthritis. To evaluate the diagnostic value of ACRF, were studied sera from patients with different classified rheumatic diseases and healthy subjects (group 1, n = 422) and 314 community cases of very early arthritis (group 2) that were classified as RA ( n = 176), non-RA ( n = 63) and undifferentiated ( n = 75) arthritides after 1 years of follow-up. ACRF were measured using a new ELISA, with results expressed as the difference between the OD value obtained on citrullinated minus that on noncitrullinated rat filaggrin (differential ACRF; dACRF). For both groups, rheumatoid factors (RF), anti-keratin autoAb (AKA) and anti-perinuclear factor (APF) were tested; for group 2, anti-CCP autoAb were also tested. Different reactivity patterns against citrullinated and noncitrullinated filaggrin were observed. Almost all sera reacting with citrullinated but not noncitrullinated filaggrin were from RA patients. Among RA and non-RA sera that recognized both forms of filaggrin, a positive result was obtained only with RA sera. For groups 1 and 2, dACRF sensitivity was 58·4% and 30·7%, and specificity for RA was 99·5% and 98·4%, respectively. In group 2, dACRF specificity for RA was better than that of RF (92·1%), APF (95·2%), AKA (96·8%) and anti-CCP (95·2%). dACRF positive predictive value was high (98·2) and close to that given by the concomitant positivity of RF and anti-CCP autoAb. Despite a high positive correlation between AKA, APF, anti-CCP and dACRF test results, they were complementary since some sera were positive for only one test. Thus, in a community setting, anticitrullinated rat filaggrin reactivity detected by a new ELISA, whose originality is based on the difference between serum's reactivities on the citrullinated and native forms of filaggrin, had a higher diagnostic value for RA than other autoAb.

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.…”

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“…However, only 25% of the anti-CCP-negative patients developed RA, compared with 93% of those who were anti-CCP positive at the beginning of the study (odds ratio [OR] 38). A study by Vittecoq et al obtained similar results (37). Those investigators found that in 314 patients with early arthritis, 90% of those who were anti-CCP positive developed RA 1 year later.…”

Peptide-coated nanotube-based biosensor for the detection of disease-specific autoantibodies in human serum

“…However, 2 of these 3 RA serum samples also had reactivity to the citrullinated peptide by microarray, ELISA and nanotube testing. Antibodies to non-citrullinated filaggrin sequences have recently been reported in the occasional RA patient (Vittecoq et al, 2004).…”