The role of type 3 muscarinic acetylcholine receptor polypeptide in the pathogenesis of Sj(o)gren's syndrome / 中华风湿病学杂志

ABSTRACT

Objective To immunize BALB/c mice with type 3 musearinic acetylcholine receptor polypeptide (M3RP) and to evaluate the role of M3RP in SS. Methods Four-week-old BALB/e mice were immunized with M3R polypeptide 213-228 (M3RP) on days 0, 14, 35, 56, and were re-immuniged on days 65, 84, 105, and one mouse was killed every 2 to 3 weeks. The mice of the control group were immunized with submaxillary gland homogenate, GST, and PBS. The animals were analyzed for the presence of anti-SSA,anti-SSB, RF, ANA, anti-a-fodrin and anti-M3RP in sera by immunofluorescenee or ELISA. The cytokines of IFN-γ IL-2 and IL-10 were measured with ELISA. Salivary glands were examined by H＆E staining and immunohistochemical analysis. Volume of water drinking by each groups were calculated. Results BALB/e mice immunized with M3RP and submaxillary gland homogenate developed an immune response directed against M3RP, α-fodrin and ANA, but no antibodies against SSA, SSB and RF were found. Furthermore, lym-phocytic infiltrates in the salivary glands of immunized animals were observed 50 days after first immunization of M3RP and submaxillary gland homogenate. The serum IFN-α in mice of M3RP, submaxillary gland ho-mogenate, GST and PBS was (62±6), (89±5), (30±5) and (19±6) pg/ml respectively, and IL-2 was (12.6±1.6), (19.8±0.4), (3.9±0.9), and (4.9±1.1) pg/ml respectively (P<0.05). No difference was found in the level of serum IL-10 among the four group. Expression of α-fodrin was found only in submaxillary gland in M3RP and submaxillary gland homogenate groups of mice, but not in PBS and GST controls when studied by immunohistochemical analysis. Conclusion These results suggest that BALB/c mice immunized with M3RP are reminiscent of human SS, and M3RP as an autoantigen participates the development of SS.