Prophylactic effects of nasal tolerance with dual analogue on experimental autoimmune myasthenia gravis in lewis rats / 中华神经科杂志

ABSTRACT

Objective To study the prophylactic effects of nasal tolerance with a dual analogue (Lys262-Ala207) on experimental autoimmune myasthenia gravis (EAMG) and observe the underlying mechanisms, the clinical and immunological changes in Lewis rats treated with dual analogue nasally. Methods The effects of the predetermined dosage of a dual analogue Lys262-Ala207 were compared at different time points, and the dual analogues or control peptides were given nasally before (Group A or CA) or on the day (Group B or CB) of immunization with acetylcholine receptor (AChR) in complete Freund's adjuvant for 10 consecutive days. The clinical scores were evaluated for 50 days after immunization. The levels of anti-AChR IgG in serum were tested by RIA. Proliferative responses of lymphocytes to no antigen, Lys262-Ala207, AChR, AChR-?100-116, MBP peptide, or Con A were tested. The numbers of mononuclear cells expressing CD4 and/or CD25 from lymph nodes were enumerated using flow cytometry. Results As compared with the corresponding control groups, Lewis rats in group A or B developed EAMG with reduced severity and loss of AChR within the neuromuscular junction. The levels of anti-AChR IgG (21.96?3.37 and 29.41?4.59) were also decreased. Proliferative responses were suppressed in response to antigen-specific stimulations in rats receiving dual analogue, whereas the numbers of CD4+CD25+ T cells were higher in group A (11.34%?1.62%) and B (8.68%?1.83%) than in their corresponding control groups. Conclusions Nasal administration with a dual analogue Lys262-Ala207, at two different time points before and on the day of immunization ameliorated muscular weakness in EAMG rats associated with decreased levels of anti-AChR IgG in serum, suppressed antigen-specific T cell proliferation and increased numbers of CD4+CD25+ T cells from lymph nodes as compared to rats receiving control peptides. The results of our study suggest that the mucosal tolerance with dual analogue should be served as an alternative maneuver in human MG.