Clinical relevance of antikeratin antibodies in rheumatoid arthritis

Abstract

Antikeratin antibodies (AKA) were found in 38 out of 96 patients with rheumatoid arthritis (RA); they appeared to be quite characteristic to this disease. There was a very low incidence of AKA positivity in the control groups, i.e., 1 out of 62 healthy subjects and 4 out of 158 other patients. With regard to the sensitivity of the test as a diagnostic tool, AKA was found to be weaker than the rheumatoid factor (RF) and the antiperinuclear factor (APF), whereas the specificity was much better than APF and RF. A clear correlation was shown between the titres of AKA and APF (p less than 0.001) and also between AKA levels and inflammation (p less than 0.02).

The cytokeratin filament-aggregating protein filaggrin is the target of the so-called "antikeratin antibodies," autoantibodies specific for rheumatoid arthritis.

“…Using indirect immunofluorescence, antibodies of the IgG class directed against components of rat esophagus and human skin have been described as highly specific for RA (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Until now, the presence of these autoantibodies, the so-called "antikeratin antibodies," in the serum of patients is the most specific serological criterion for the disease.…”

“…These antibodies are clearly autoantibodies since they also react with the stratum corneum of human epidermis (6)(7)(8)(9). They have been found to be highly specific for the disease (6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and their detection is now widely used as a diagnostic test for RA. Although their role has not yet been defined, they are associated with more active and /or severe forms of RA (13)(14)(15)(16) and they are detected at early stages ( 16) and even before the onset ofjoint symptoms ( 17), suggesting their involvement in the pathophysiology of the disease.…”

The Devil in the Details: The Emerging Role of Anticitrulline Autoimmunity in Rheumatoid Arthritis

“…The presence of IgM ACPA-secreting B cells in synovial fluid is indicative of a continuous activation of B cells specific for citrullinated Ags from naive precursors, suggesting an Ag-driven proliferation and maybe local differentiation of these cells. The ACPA response became prime suspect in the pathogenesis of RA once it became clear that, while being found in 60 -70% of patients with RA, ACPAs display a unique specificity for RA and are rarely detected in other diseases or in healthy controls (13,(33)(34)(35)(36). Remarkably, using recently developed ELISAs containing cyclic citrullinated peptides, ACPAs of the IgG isotype have been detected up to nine years before symptoms of RA occurred (37,38).…”

“…Later on, also anti-keratin Abs (AKAs) (11) were identified by using rat or human esophagus cryostat sections for detection. Despite the fact that several research groups have recognized the clinical and diagnostical value of these Abs, especially because of their high specificity for RA (12)(13)(14)(15), APFs and AKA never became very popular. This was mainly a consequence of the fact that testing their presence was more laborious than the RF test, which soon became the standard laboratory test for RA.…”

Antikeratin antibodies: diagnostic and prognostic markers for early rheumatoid arthritis.

“…The mean age at entry was 44-4 years (range 19-65). All patients had early RA with a disease duration of less than one year (mean 7-8 months, range [3][4][5][6][7][8][9][10][11][12]. At the time of diagnosis, 48 patients (68%) were seropositive by the Rose-Waaler test (titre ¢ 1/64), 41 patients (58%) were HLA-DR4 positive, and joint erosions were present in 23 (32%) of patients.…”