In this cross-sectional study we enrolled 42 patients with MG and 36 volunteers. We employed enzyme-linked immunosorbent assays to determine the concentration of soluble RAGE (sRAGE) and high mobility group box 1 (HMGB1) in serum of patients and volunteers. In a subpopulation of patients we measured the serum levels of endogenous secretory (es) RAGE and various RAGE ligands, such as S100B, S100A8 and advanced glycation endproducts (AGE-CML). Reported are means and standard error mean.
We found significantly reduced levels of the soluble receptors sRAGE and esRAGE in patients with MG compared to volunteers without MG (sRAGE [pg/ml] 927.2 卤 80.8 vs. 1400.1 卤 92.4; p < 0.001; esRAGE [pg/ml] 273.5 卤 24.6 vs. 449.0 卤 22.4; p < 0.001). Further categorization of patients with MG according to the distribution of muscle involvement revealed the following sRAGE concentrations: generalized MG 999.4 卤 90.8 and ocular MG 696.1 卤 161.8 (vs. control; One-way ANOVA: p < 0.001; Post hoc analysis: generalized vs. ocular MG: p = 0.264, generalized MG vs. control: p = 0.008, ocular MG vs. control: p = 0.001). In patients with detectable antibodies specific for acetylcholine receptors (Anti-AChR positive) the sRAGE concentration was 970.0 卤 90.2 compared to those without (seronegative) 670.6 卤 133.1 (vs. control; One-way ANOVA: p < 0.001; Post hoc analysis: Pos vs. Neg.: p = 0.418, Pos vs. control: p = 0.003, Neg. vs. control: p = 0.008). We next investigated the role of RAGE ligands in MG. The concentrations of RAGE ligands in patients with MG and controls were as follows: (HMGB1 [ng/ml] 1.7 卤 0.1 vs. 2.1 卤 0.2; p = 0.058; S100B [pg/ml] 22.5 卤 22.5 vs. 14.4 卤 9.2; p = 0.698; S100A8 [pg/ml] 107.0 卤 59.3 vs. 242.5 卤 103.6; p = 0.347; and AGE-CML [ng/ml] 1100.8 卤 175.1 vs. 1399.8 卤 132.8; p = 0.179).
Our data suggest a role for the RAGE pathway in the pathophysiology of MG. Further studies are warranted to elucidate more about this immunological axis in patients with MG.