Keratinocytes from patients with lupus erythematosus show enhanced cytotoxicity to ultraviolet radiation and to antibody-mediated cytotoxicity

Keratinocyte cytotoxicity is an important component of the immunopathology of photosensitive lupus erythematosus, and antibody-dependent cell-mediated cytotoxicity (ADCC) has been shown to be an important mechanism by which a utoantibodies, especially those specific for SS-A/Ro, can induce keratinocy te damage in models of photosensitive lupus. We provide further evidence th at keratinocytes from patients with photosensitive lupus show significantly greater ultraviolet radiation (UVR)-induced cytotoxicity, and that ADCC of these targets is especially enhanced by autologous patient's serum or by a nti-SS-A/Ro(+) sera. Keratinocytes from normal uninvolved skin of 29 patien ts with cutaneous lupus erythematosus (LE) were grown in cell culture and t ested as targets in cytotoxicity experiments in vitro. Cultured keratinocyt es from patients with systemic lupus erythematosus (SLE) and subacute cutan eous lupus erythematosus (SCLE) showed significantly greater cytotoxicity f ollowing UVR treatment than did keratinocytes from normal adult controls or from neonatal foreskins (P < 0.01). The same cultures also showed greater UVR-induced binding of IgG from fractionated anti-SS-A/Ro(+) preparations. ADCC experiments were also performed using keratinocytes cultured from pati ents with SLE, SCLE, discoid lupus erythematosus (DLE), and normal controls . When keratinocytes were incubated in autologous serum plus a standard mon onuclear cell effector population, the percentage of ADCC observed was sign ificantly greater in cultures containing keratinocytes and sera from the SL E and SCLE patients (P < 0.001). When cultured keratinocytes were added to different IgG antibody probes, plus standard mononuclear effector populatio ns, greater ADCC was seen using the anti-SS-A/Ro probe and keratinocytes fr om patients with SLE or SCLE. With normal human neonatal keratinocyte targe ts, the anti-SS-A/Ro probe induced greater ADCC than that seen with anti-ss DNA or normal human serum. We have shown that keratinocytes from patients w ith some forms of lupus erythematosus (SLE and SCLE) show greater cytotoxic ity in vitro when irradiated with UVR, and greater susceptibility to ADCC w hether the antibody source is their own serum or an anti-SS-A/Ro probe.