Specific T-cell proliferation to myelin peptides in relapsing-remitting multiple sclerosis

Abstract

Background: The identification of major immunogenic peptides in multiple sclerosis (MS) is of great importance for the development of antigen-specific therapies. Cellular reactivity against a selected mix of seven myelin peptides was evaluated in vitro. The evolution of this reactivity over time and its correlation with clinical variables was also analysed. Material and methods: Forty-two patients with MS, 15 with other demyelinating diseases and 40 healthy donors (HD) were studied. Cell proliferation was measured by 3[H] thymidine incorporation into samples obtained at 0, 3, 6 and 12 months of MS patient follow-up. Results: A positive reaction to the peptide mix was detected in 31 of the 42 patients (74%), 12 of the 40 HD (30%) and 6 of the 15 (40%) patients with other demyelinating diseases. Patients with positive proliferation had greater disability (EDSS score, 3 [1-5.5] vs. 1.0[1-2], P = 0.021), higher number of relapses (7 ± 4.1 vs. 3 ± 1.2, P < 0.001) and shorter time since the last relapse (9 ± 7.5 vs. 32 ± 12.3 months, P = 0.036). After 12 months of follow-up, cell reactivity was maintained in 33 patients (78%). Conclusion: A high percentage of patients exhibit a significant and maintained reactivity to myelin peptides over time. Therefore, this mix may be useful as a source of antigen in the development of protocols aimed at inducing specific tolerance in MS.

Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration

“…Previously, it was shown that proteins expressed in the myelin sheath, protecting neuronal axons of the CNS, are an important target of the autoreactive T cell response 7–9. Also in our hands, ex vivo T cell reactivity against a mix of seven immunodominant myelin-derived peptides could be demonstrated in RRMS patients as compared with healthy controls and patients with other neurological disorders 10. Although the underlying cause of the loss of tolerance towards myelin antigens has not been elucidated yet, one ultimate aim in the treatment of MS is to reestablish antigen-specific immune tolerance towards CNS structures 11–15.…”

Regulatory role of vitamin D in T-cell reactivity against myelin peptides in relapsing-remitting multiple sclerosis patients

“…Previously, we demonstrated that T-cell proliferation against a selected mix of 7 myelin peptides was more common in RRMS patients than in HC, which supports their pathogenic significance in MS [21]. Interestingly, patients with positive T-cell proliferation against myelin peptides had low levels of plasma 25(OH)D. Correale et al [4] demonstrated by in vitro coculture with 1,25(OH)2D3 that the proliferation of myelin basic protein (MBP)-specific T cells was significantly inhibited.…”

Stable antigen‐specific T‐cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients

“…Furthermore, our group has recently confirmed the reactivity to the aforementioned set of immunodominant peptides in peripheral blood T cells from MS patients compared with healthy controls (HCs) [5]. Hence, specific inhibition or depletion of autoreactive T cells represents an interesting goal for future therapies aiming to restore peripheral tolerance in autoimmune diseases such as MS. Current treatments for relapsing-remitting MS (RR-MS) patients decrease the frequency of relapses and reduce inflammatory activity in a nonspecific manner, but their effect on disease progression is still unclear [6,7].…”