The Antiperinuclear Factor (APF) and Antikeratin Antibodies (AKA) in Rheumatoid Arthritis

Abstract

The diagnosis of rheumatoid arthritis (RA) is primarily based on clinical symptoms, so it is often difficult to diagnose RA in very early stages of the disease. A disease-specific autoantibody that could be used as a serological marker would therefore be very useful. Most autoimmune diseases are characterized by a polyclonal B-cell response targeting multiple autoantigens. These immune responses are often not specific for a single disease. In this review, the most important autoantibody/autoantigen systems associated with RA are described and their utility as a diagnostic and prognostic tool, including their specificity, sensitivity and practical application, is discussed. We conclude that, at present, the antibody response directed to citrullinated antigens has the most valuable diagnostic and prognostic potential for RA.

The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide

“…Although studied extensively (for review, see ref. 8), the conventional indirect immunofluorescencebased APF test has never been put into general use as a diagnostic test for RA. Reasons for this restraint were the dependence on the availability of suitable buccal cell donors, the laborious indirect immunofluorescence technique, and the problematic standardization.…”

“…Other autoantibody-antigen systems described in RA are RA33 (3), Sa (4), p68 (5), calpastatin (6), and perinuclear factor (7)(8)(9). Anti-RA33 antibodies, however, are also found in about one-third of systemic lupus erythematosus and mixed connective tissue disease (MCTD) patients (1) and, thus, are not very specific for RA.…”

“…The APF test, although specific for RA, has never been put into general use as a diagnostic test. Reasons for this restraint were the subjective and laborious immunofluorescence technique, the necessity to use preselected buccal cell donors, and the problematic interlaboratory standardization (8). Hoet and coworkers (9) described colocalization of APF with a monoclonal antibody specific for the protein (pro)filaggrin in buccal mucosa cells.…”

The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies.

“…Their occurrence is independent of the age and sex of the patients (6,16,30,31). Their presence and/or titers have been found to be correlated to each other (9,19,21,22,38), to the presence of rheumatoid factors (6,7,16,30), and to the severity and activity of the disease (22, 25-28, 30, 35). Furthermore, APF and AKA are both independent of the disease duration (15,16,18,29,30), appear early, and may even precede the clinical manifestations of RA (10,21,34,35).…”

Current methods for laboratory diagnosis of rheumatoid arthritis

“…В 1964 г. при изучении антиядерных антител у больных РА был выявлен АПФ, показавший высокие значения чувст-вительности (40-91%) и специфичности (73-99%) [14][15][16][17]. Эти аутоантитела присутствовали как в сыворотке, так и в синовиальной жидкости больных [45].…”