Reactivity of serum antibodies to the keratin layer of rat esophagus in patients with rheumatoid arthritis

Abstract

Serum antibodies reactive with the keratin layer of rat esophagus (AKA) were found in 46 of 80 (57.5%) rheumatoid arthritis (RA) patients. In contrast, A M were present in only 7 of 82 (9.5%) patients with other types of rheumatic disorders and in 2 of 47 (4.2%) healthy subjects. AKA were not specific for RA, however, because in the former group, A M were present in 4 of 20 (20%) systemic sclerosis patients and in 3 of 12 (25%) ankylosing spondylitis patients. AKA belong predominantly to the IgG class and are complement fixing. Although found in some RA joint fluids, AKA were not selectively concentrated in the joint fluid. Absorption of RA serum with type I human collagen or with human epidermal keratin did not remove AKA activity. The frequency of AKA in RA patients both negative and positive for DR4 was equal. There was no relationship between the frequency of AKA and the occurrence of other serum autoantibodies such as antibodies to intermediate filaments, smooth muscle, and nuclear antigens. Serum antibody reactive with human stratum corneum found in patients with psoriatic arthritis was

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.…”

“…In 1979, Young et al (6) showed, using indirect immunofluorescence, the presence, in rheumatoid sera, of IgG antibodies labeling the stratum corneum of rat esophagus epithelium. 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.…”

“…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 rheumatoid arthritis-associated autoantibodies to filaggrin label the fibrous matrix of the cornified cells but not the profilaggrin-containing keratohyalin granules in human epidermis

“…These antibodies were therefore catted antikeratin antibodies (AKA), in the absence of any biochemical characterization of the antigen they recognized. However, this labelting was found to be unmodified either by pretreatment of rat oesophagus cryosections with a rabbit anti-serum to human cytokeratins, or by preabsorption ofthe RA sera with human cytokeratins [5]. In a recent work.…”

“…IgG antibodies to the cornified epithelium of rat oesophagus have been largely demonstrated to occur specifically in rheumatoid arthritis (RA) sera ( [2][3][4][5][6][7][8][9][10][11][12][13], reviewed in [14]). The RA-specific antibodies show a typical indirect immunofluorescence (T!F) labetling pattern restricted to the upper epithetiat tayer, the stratum corneum.…”