In subacute cutaneous lupus eryhematosus (SCLE) the cutaneous antigens constitute the main source of Ro and La autoantigens. The aim of this investigation was to demonstrate if UV light increases the availability of Ro autoantigen in the skin, also the blocking effect of Ac-DEVD-CMK a caspase inhibitor was assessed. For this purpose newborn Balb/c mice were UVB irradiated (5–30 mJ/cm2) equivalent to a moderate to severe sunburn. Animals were injected with monoclonal anti-Ro antibodies from SCLE patients. Apoptosis was also induced by anti-Fas antibody injection. Skin samples were examined by direct immunofluoresence, by TUNEL, and the expression of caspase 3 by RT-PCR. Major findings of present studies were: 1. UVB irradiation and anti-Fas induced apoptosis of keratinocytes. 2. Apoptosis redistribute the Ro antigen on cell surface and is better triggered by Ro antibody. 3. The caspase 3 inhibitor Ac-DEVD-CMK decreases the availability of Ro autoantigen in epidermis and prevents deposition of anti-Ro. In conclusion, the caspase pathway would be blocked to avoid anti-Ro deposition along skin; this finding would be a prospect in the treatment of SCLE patients.

Fas ligand (L) is a membrane protein from the tumor necrosis factor (TNF) family. It induces apoptosis upon contact with its Fas/CD95/APO1 receptor. Trimerization of FasL on the surface of effector cells is essential in the binding of the Fas trimer of the target cells. The receptor then recruits an adaptor and caspase-like proteins which lead apoptosis. This paper reports on the fate of FasL in HEp-2 cells committed to apoptosis by induction with campthotecin. Our main results demonstrated that in non-apoptotic cells, FasL aggregates in the cytoplasm forming trimers of 120 kDa. Apoptosis increases the trimeric FasL species, but also induces its dissociation into monomers of 35 kDa. In conclusion, camptothecin appears to perturb the Fas and FasL segregation in the cytoplasm by promoting the transit of FasL to the cell surface, thus fostering a process of autocrine or paracrine apoptosis. FasL is trimerized prior to Fas/FasL complex formation, and after apoptosis, FasL undergoes an intense turnover.

Background: The autoimmunity associated with environmental pollutants such as heavy metals is a phenomenon that has been described previously. The aim of the present study investigated the relationship between autoimmunity and lead pollutants in a cohort of children who lived in a mining settlement. Methods: Children were studied clinically and serologically. The serum lead concentration was measured by atomic absorption spectrometry, and antinuclear antibodies were analysed by immunofluorescence, ELISA and Western blot. Results: None of the studied children displayed any autoimmune disease. The lead concentration in the control group was negligible, at 0.10 ± 011 µg. L -1 . In contrast, the study group had values of 12.72 ± 0.5 µg. L -1 . The differences between the groups were significant (p< 0.0001). In addition, control sera were negative for antinuclear antibodies (ANA), while the sera of children living near the mining settlement showed ANA-positive titres (p< 0.001). These autoantibodies mainly recognized antigens associated with dividing cells, such as the mitotic apparatus and centrioles. Conclusion: The present results show how metallic pollutants induce environmentally associated autoimmunity and are reflected by antinuclear antibodies. This research should prompt us to take greater caution and implement permanent monitoring to ensure a healthy environment.

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