CIRCULATING T-CELLS OF PATIENTS WITH ACTIVE PSORIASIS RESPOND TO STREPTOCOCCAL M-PEPTIDES SHARING SEQUENCES WITH HUMAN EPIDERMAL KERATINS

Psoriasis is a T-cell mediated inflammatory skin disease which has bee n associated with group A, beta-haemolytic streptococcal infections. F our 20 a.a. long M6-peptides sharing 5-6 a.a. sequences with human epi dermal keratins were identified. To investigate the role of potentiall y cross-reactive T cells in the pathogenesis of psoriasis, interferon- gamma (IFN-gamma) and interleukin-4 (IL-4) responses of circulating T cells to these peptides were analysed by ELISPOT and RT-PCR in 14 psor iatic patients, 12 healthy individuals and six patients with atopic de rmatitis (AD). Untreated psoriatic patients' responses were significan tly higher to these peptides than healthy and AD controls, while respo nses to a control M6-peptide, not sharing sequences with keratin, were negligible in all groups. No difference was found in response to stre ptokinase/streptodornase (SK/SD). M6-protein and peptides exclusively elicited IFN-gamma production, with little IL-4 production, even in AD patients. Interferon-gamma responses to all the M6-peptides were abol ished after successful treatment of psoriatic patients, but responses to SK/SD were unaffected. The results indicate that active psoriasis i s associated with Th1-like cells responding to streptococcal M6-peptid es sharing sequences with human epidermal keratin. This is consistent with the hypothesis that psoriasis may be induced and exacerbated in s usceptible individuals by M-protein specific Th1-like cells that cross -react with human epidermal keratin.