Heterogeneity in the expression of ro and la antigens in human skin

Abstract

Objective. To determine whether there are variations in the expression of Ro and La antigens in human skin.Methods. Levels of expression of Ro andor La antigens in 26 specimens of normal human skin (11 sun-exposed, 15 sun-protected) were measured by indirect immunofluorescence with monospecific antisera.Results. Levels of expression of both antigens varied by more than 2,000-fold in the skin of different individuals. There usually was a correlation between the levels of expression of Ro and La antigens in the same skin specimen. There was no correlation found between the levels of Ro or La antigen expression and sun exposure, nor was there a correlation found between levels of antigen expression and location of the skin on the body.Conclusion. There is a marked heterogeneity in the expression of both Ro and La antigens in the skin of different individuals. The present study findings suggest that the levels of expression of these antigens may play a role in the propensity of some individuals to develop anti-Ro or anti-La antibodies andor skin lesions associated with the presence of these antibodies.Antibodies to Ro and La RNP particles are frequently detected in the serum of patients with systemic lupus erythematosus (SLE) and other connective tissue diseases (1-3). The incidence of these antibodies is particularly high in forms of lupus erySupported in part by USPHS research grants P-30-CA-16087, AR-39749, and R01-AM-27663-09, and by funds from the Rudolph Baer Foundation.Yayoi Niimi, MD: Nippon Medical School, Tokyo, Japan; Demetris Ioannides, MD: Aristotelian University Medical School, Thessaloniki, Greece; Jill Buyon, MD: Hospital for Joint Diseases, New York University School of Medicine, New York, NY; JeanClaude Bystryn, MD: New York University School of Medicine, New York, NY.Address reprint requests to Jean-Claude Bystryn, MD, NYU Medical Center, 560 First Avenue, New York, NY 10016.Submitted for publication April 19, 1994; accepted in revised form March 7, 1995. thematosus that are associated with photosensitivity, such as subacute cutaneous LE (SCLE) and neonatal LE, in which Ro and La antibodies are present at very high titers in >80% and >60% of the patients, respectively (4-7). The reason for this is not yet known. One possibility is that sun exposure increases the expression of Ro and/or La antigens in human skin. To address this issue, we studied the levels of expression of these antigens in human skin, obtained from both sun-exposed and sun-protected areas of the body. Unexpectedly, the results showed that, although there was little correlation between sun exposure and the expression of Ro and La antigens in human skin, there was a striking variation in the expression of these antigens between different individuals. MATERIALS AND METHODSAntisera. Two antisera were used in this study; one contained antibodies that react predominantly against Ro polypeptides, and the other contained antibodies with predominant reactivity against La polypeptides. These sera were selected from among several hundred...

Expression of SS-A/Ro and SS-B/La Antigens in Skin Biopsy Specimens of Patients With Photosensitive Forms of Lupus Erythematosus

“…However, we recently found that there is a marked variation in the expression of Ro and La antigens in keratinocytes among patients with LE. 3 Moreover, it was demonstrated that both antigens are expressed on the surface of cultured human keratinocytes irradiated with UV light, 4,5 suggesting that autoantibodies can be formed in response to exposure of sequestered nuclear autoantigens following exposure to sunlight. 6 These observations suggest the hypothesis that both Ro and La antibodies and photosensitivity appear preferentially in patients who are high expressors of these antigens in their skin.…”

“…It does not seem to be related to age or sex. 3 It is not due to differences in the specificity or binding affinity of the Ro or La antibodies, since the same serum samples were used to test all skin specimens, or to regional variations in antigen expression, since the specimens of skin in all cases were obtained from the same anatomical location. However, the possibility that the changes in antigen level reflect changes in the accessibility of the antigen to antibody, rather than to the actual amount of antigen, has not been excluded.…”

“…The correlation coefficients between anti-La while serum sample 2 reacted strongly with the 60-kd Ro antigen and weakly with the 52-kd Ro antigen. The MOLT-4 cells were specifically chosen because previous studies 3,8,9 demonstrated that these cells provide an excellent source of the Ro and La protein components that are reliably recognized in immunoblot analysis in serum samples containing the respective antibodies. Serum sample 3 with anti-La reactivity showed a strong positive reaction in the results of ELISA using rabbit thymus as the source of the La antigen (Ͼ30 SDs above control) and showed a negative reaction using bovine spleen as the source of the Ro antigen.…”

Spectrum and clinical significance of autoantibodies against transfer RNA

“…However, most patients with these autoantibodies do not develop skin lesions, and in the present study only 18 of 205 patients (8.8%) developed recurrent erythema. These results suggest that additional pathogenic factors, as well as overexpression of Ro/SSA or La/SSB autoantigens, are active in involved skin (41). Hoshino et a1 demonstrated that there is no significant association between reactivity to epitopes and different types of recurrent erythema (40).…”

“…For categorical variables, frequencies of observations were determined and were compared using Fisher's exact test. When deproteinized RNA was used as antigen, 15 serum samples (patients 6,7,19,20,21,22,24,26,27,28,32,33,35,38,41) precipitated naked tRNAs ( Figure 1B). Four of 6 patients who had overlap syndrome and tRNA-associated antibodies were diagnosed as having secondary SS.…”