IMPACT OF ULTRAVIOLET-IRRADIATION ON EXPRESSION OF SSA RO AUTOANTIGENIC POLYPEPTIDES IN TRANSFORMED HUMAN EPIDERMAL-KERATINOCYTES/

SSA/Ro autoantibodies are frequently found in various autoimmune disor ders including subacute cutaneous and neonatal lupus erythematosus. SS A/Ro patient sera precipitate a ribonucleoprotein complex consisting o f multiple polypeptides and small RNA molecules (hY RNA). Such sera re act in Western blot with at least four antigenically distinct proteins having molecular weights of 52-60 kD. Several laboratories have repor ted increased binding of anti-SSA/Ro patient serum to viable cultured human epidermal keratinocytes following UVB irradiation. However, it i s currently unknown which SSA/Ro molecule(s) might be responsible for this increased antibody binding to WE irradiated keratinocytes. To add ress this question, we studied the effect of WE irradiation on the exp ression of three different polypeptide components of the SSA/Roautoant igen complex (60 kD SSA/Ro, 52 kD SSA/Ro, and 46 kD SSA/Ro (calreticul in) in A431 cells, a transformed human epidermal keratinocyte cell Lin e. Total cellular and cell surface expression of each SSA/Ro antigenic polypeptide was examined by a whole cell ELISA and FAGS using rabbit anti-synthetic peptide antisera as probes. Our results suggest that bo th total cellular and cell surface calreticulin, but not the 60 and 52 kD SSA/Ro polypeptides, is increased after 100 J/M(2) of WE irradiati on, indicating that perturbed calreticulin expression may be primarily responsible for the UVB-induced increased binding of anti-SSA/Ro to k eratinocytes. These results suggest that calreticulin could be a criti cal component of the SSA/Ro ribonucleoprotein complex that is involved in the pathogenesis of anti-SSA/Ro-associated photosensitive LE skin lesions.