The Journal of Rheumatology 2002; 29:2 276 From UF “Autoimmunité,” Laboratoire d’Immunologie, Service de Rhumatologie, Centre Hospitalier Lyon-Sud; and Ecole Nationale Vétérinaire de Lyon, Lyon, France. C. Ferraro-Peyret, PhD; A. Desbos, Fellow; R. Bihannic, Fellow; C. Genestier, Fellow; S. Veber, Fellow; C. Veysseyre-Balter, PhD; J.C. Monier, MD, Professor; N. Fabien, PhD, UF “Autoimmunité,” Laboratoire d’Immunologie; J. Tebib, MD, Professor; M.C. Letroublon, Fellow, Service de Rhumatologie, Centre Hospitalier Lyon-Sud; E. Benoit, MD, Professor, Ecole Nationale Vétérinaire de Lyon. Address reprint requests to Dr. N. Fabien, UF “Autoimmunité,” Centre Hospitalier Lyon-Sud, 69495 Pierre Bénite Cedex, France. Submitted April 17, 2001; revision accepted August 29, 2001. Rheumatoid arthritis (RA) is the most frequent human systemic autoimmune disease. Diagnosis is still difficult, especially at the onset of clinical symptoms. Like other non- organ-specific systemic autoimmune diseases, RA shows a wide variety of circulating autoantibodies (Ab) such as rheumatoid factor (RF), anticollagen, anti-Sa, anticalpas- tatin, antiperinuclear (APF), antistratum corneum (ASC), and antifilaggrin (AFA) Ab 1-11 . RF is the only Ab chosen to be a biological criterion in the diagnosis of RA following the criteria of the American Rheumatism Association (ARA) 12 . However, this marker shows poor diagnostic specificity, as it is found in various other autoimmune diseases and in normal healthy persons 13 . Further, its detection is not helpful at the onset of disease, since positivity usually appears after the first year of active arthritis 14 . Among the wide variety of circulating Ab in RA, APF and ASC/AFA are increasingly recognized as major Ab with diagnostic significance because of their higher specificity and sensitivity compared to the other Ab. Indeed specificity of APF reaches 74 to 99% 15-17 , with a mean sensitivity of 59.7%. Specificity of ASC/AFA varies between 72 and 100%, with a mean sensi- tivity of 45% 7,18-25 . Besides this high specificity this marker does not appear to be affected by the duration of the disease compared to RF 2,26 . APF recognize antigens in perinuclear granules located in superficial cells in human buccal mucosa squamous epithelium. Classically APF is detected by indi- rect immunofluorescence (IIF) on fresh human buccal mucosa cells. Inadequate standardization of this substrate, i.e., selection of “good donors,” results in high interlabora- tory variations for assay sensitivity 27 . Consequently APF are not considered a suitable marker for RA diagnosis. ASC/AFA, mainly of the IgG isotype, were described by Young, et al 28 and were initially called antikeratin or antis- tratum corneum antibody. Indeed, ASC are essentially detected by IIF using cryosections of rat esophagus giving rise to a laminar labelling within the stratum corneum of the epithelium. Later filaggrin was identified as the target antigen of the ASC in the stratum corneum 8,9 . Filaggrin of an apparent molecular weight of 37 kDa derives from the Improvement in Diagnosis of Rheumatoid Arthritis Using Dual Indirect Immunofluorescence and Immunoblotting Assays for Antifilaggrin Autoantibodies: A Retrospective 3 Year Study CAROLE FERRARO-PEYRET, JACQUES TEBIB, AGNES DESBOS, RENE BIHANNIC, CHRISTELLE GENESTIER, MARIE-CLAUDE LETROUBLON, SOPHIE VEBER, ETIENNE BENOIT, CECILE VEYSSEYRE-BALTER, JEAN-CLAUDE MONIER, and NICOLE FABIEN ABSTRACT. Objective. To determine the clinical usefulness of measuring antistratum corneum (ASC) and antifi- laggrin autoantibodies (AFA) to discriminate between rheumatoid arthritis (RA) and other rheumatic or autoimmune diseases, using an indirect immunofluorescence (IIF) assay, along with a comple- mentary immunoblotting technique (IB) when IIF detection of ASC was negative. Methods. Sera from 346 patients were studied: 189 sera from patients with RA seen in the same clinic, 92 from patients with non-RA rheumatic diseases, 24 from nonrheumatic autoimmune diseases, and 41 from healthy blood donors. ASC and AFA were detected using IIF and IB, respec- tively. Results. ASC detection using IIF showed a specificity of 97.5% for RA with 44.4% sensitivity. When both IIF and IB techniques were used, sensitivity for RA increased significantly (up to 53.4%; p < 0.01) with no decrease in specificity (p < 0.01). Conclusion. These data confirm the usefulness of 2 different techniques performed simultaneously for detecting ASC/AFA, and the usefulness of these biological markers for discriminating between RA and other rheumatic diseases in clinical practice. (J Rheumatol 2002;29:276–81) Key Indexing Terms: ANTIFILAGGRIN AUTOANTIBODY RHEUMATOID ARTHRITIS IMMUNOBLOTTING Personal non-commercial use only. The Journal of Rheumatology Copyright © 2002. All rights reserved. www.jrheum.org Downloaded on September 5, 2021 from