Anti-idiotype antibodies neutralize in vivo the blistering effect of Pemphigus foliaceus IgG.

Idiotypes are molecular clues used to explore the specificity and diversity of immune response. In the present study, anti-idiotype antibodies were used to neutralize the pathogenic effects induced by the injection of pemphigus immunoglobulin(Ig)G into BALB/c mice. To achieve our goal, antidesmoglein 1 IgG was obtained from a patient with pemphigus foliaceus with high titer of antiepithelial antibodies. The IgG was isolated by ion exchange chromatography, then digested by pepsin. F(ab')2 fragments were purified in Sephacryl S-300 and injected in rabbits to produce anti-idiotype antibodies. The rabbit sera reacted with the pemphigus F(ab')2 fragments. Eleven pemphigus foliaceus sera were recognized by the anti-idiotype serum at the light or heavy chains whereas bullous pemphigoid and normal IgG were negative. Neonatal BALB/c mice injected with pemphigus IgG developed intraepidermal blisters, mimicking the clinical and immunopathological features of the pemphigus. In contrast, the animals treated with anti-idiotype antibodies and pemphigus IgG did not develop blisters. Thus, anti-idiotype antibodies neutralize in vivo the pathogenic effects of pemphigus IgG.

UV-A irradiation induces transcription of IL-6 and TNF alpha genes in human keratinocytes and dermal fibroblasts.

OBJECTIVE: To determine whether UV-A irradiation induces synthesis of inflammatory cytokines in the skin. METHODS: Human keratinocytes and dermal fibroblasts were cultured and exposed to various doses of UV-A radiation. The cellular distribution of IL-6 and TNF alpha was determined by indirect immunofluorescence and by flow cytometry with monoclonal anti-IL-6 and anti-TNF alpha antibodies. Cytokine production was measured in the supernatants using an ELISA. IL-6 and TNF alpha transcription induced by UV-A was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification. RESULTS: IL-6 and TNF alpha were detected in small amounts in nonUV-A-irradiated cell. UV-A exposure was followed by significant increases in IL-6 and TNF alpha expression and by small increases in IL-6 and TNF alpha levels in culture supernatants. RT-PCR demonstrated a UV-A-mediated increase in the transcription of IL-6 and TNF alpha genes. CONCLUSION: Synthesis of IL-6 and TNF alpha can be induced by UV-A irradiation. This effect of UV-A may contribute to the inflammatory skin changes seen during lupus flare-ups after sun exposure.