Related Experiment Videos
Circulating T cells of patients with active psoriasis respond to streptococcal M-peptides sharing sequences with
H Sigmundsdottir1, B Sigurgeirsson, M Troye-Blomberg
1Department of Immunology, National University Hospital, Reykjavik, Iceland.
Abstract:
Psoriasis is a T-cell mediated inflammatory skin disease which has been associated with group A, beta-haemolytic streptococcal infections. Four 20 a.a. long M6-peptides sharing 5-6 a.a. sequences with human epidermal keratins were identified. To investigate the role of potentially 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 psoriatic patients, 12 healthy individuals and six patients with atopic dermatitis (AD). Untreated psoriatic patients' responses were significantly higher to these peptides than healthy and AD controls, while responses to a control M6-peptide, not sharing sequences with keratin, were negligible in all groups. No difference was found in response to streptokinase/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 abolished after successful treatment of psoriatic patients, but responses to SK/SD were unaffected. The results indicate that active psoriasis is associated with Th1-like cells responding to streptococcal M6-peptides sharing sequences with human epidermal keratin. This is consistent with the hypothesis that psoriasis may be induced and exacerbated in susceptible individuals by M-protein specific Th1-like cells that cross-react with human epidermal keratin.
Insights
Psoriasis may be triggered by streptococcal M6-peptides that mimic human skin proteins. T-cells (Th1-like) responding to these peptides cross-react with keratin, potentially causing psoriasis flares.
Area of Science:
- Immunology
- Dermatology
- Microbiology
Background:
- Psoriasis is a T-cell mediated inflammatory skin condition.
- Group A, beta-haemolytic streptococcal infections are linked to psoriasis.
- Specific streptococcal M6-peptides share sequences with human epidermal keratins.
Purpose of the Study:
- Investigate the role of T-cells cross-reactive to streptococcal M6-peptides in psoriasis pathogenesis.
- Analyze interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) responses to M6-peptides in psoriatic patients and controls.
Main Methods:
- ELISPOT and RT-PCR assays were used to measure T-cell responses.
- Circulating T-cells from psoriatic patients, healthy individuals, and atopic dermatitis patients were analyzed.
- Responses to four M6-peptides sharing keratin sequences and control peptides were assessed.
Main Results:
- Untreated psoriatic patients showed significantly higher T-cell responses to M6-peptides compared to controls.
- Responses were predominantly IFN-gamma mediated (Th1-like), with minimal IL-4 production.
- Successful psoriasis treatment abolished M6-peptide specific IFN-gamma responses, while streptokinase/streptodornase responses remained unaffected.
Conclusions:
- Active psoriasis is associated with Th1-like T-cells that react to streptococcal M6-peptides sharing keratin sequences.
- This supports the hypothesis that psoriasis can be induced or worsened by M-protein specific T-cells cross-reacting with human epidermal keratin.