THE RHEUMATOID ARTHRITIS-ASSOCIATED AUTOANTIBODIES TO FILAGGRIN LABELTHE FIBROUS MATRIX OF THE CORNIFIED CELLS BUT NOT THE PROFILAGGRIN-CONTAINING KERATOHYALIN GRANULES IN HUMAN EPIDERMIS
M. Simon et al., THE RHEUMATOID ARTHRITIS-ASSOCIATED AUTOANTIBODIES TO FILAGGRIN LABELTHE FIBROUS MATRIX OF THE CORNIFIED CELLS BUT NOT THE PROFILAGGRIN-CONTAINING KERATOHYALIN GRANULES IN HUMAN EPIDERMIS, Clinical and experimental immunology, 100(1), 1995, pp. 90-98
Since they were first described, serum IgG antibodies to the stratum c
orneum of rat oesophagus epithelium, highly specific for rheumatoid ar
thritis (RA), have been consensually called antikeratin antibodies (AK
A). However, we recently demonstrated that they actually recognize thr
ee new proteins of rat oesophagus epithelium distinct from cytokeratin
s, and also human epidermal filaggrin. In this work we provided furthe
r evidence that AKA and RA-associated anti-filaggrin autoantibodies ar
e the same antibodies. Moreover, analysing by indirect immunofluoresce
nce on human skin a large series of 212 well characterized RA sera and
anti-filaggrin autoantibodies purified from RA sera by affinity chrom
atography, we demonstrated the specific binding of AKA to the stratum
corneum of human epidermis and the absence of any staining of the gran
ular keratinocytes. This binding was confirmed and the AKA antigen pre
cisely localized in human epidermis by immunoelectron microscopy. The
antigen was found to be restricted to the filaggrin-containing intrace
llular fibrous matrix of the corneocytes, up to the desquamating cells
. In contrast, MoAbs directed to human filaggrin and to profilaggrin,
its precursor, not only stained the intracellular matrix of the lower
corneocytes but also the keratohyalin granules of the granular cells,
where profilaggrin is stored. These results reinforced by the absence
of immunoblotting reactivity of RA sera to profilaggrin suggest that t
he epitopes recognized by AKA are absent from profilaggrin. Their iden
tification may provide more insight into the pathogenesis of RA.