The complement and immunoglobulin levels in NMO patients

Since the discovery of aquaporin-4 (AQP4) antibody a decade ago, neuromyelitis optica (NMO) has been distinguished from multiple sclerosis (MS). MS mainly features T lymphocyte-oriented autoimmune responses while NMO is more precisely influenced by humoral immunity, among which the complement activation has always been reckoned as an important mechanism. The AQP4 antibody, namely NMO-IgG, adds to new evidence of how complement affects the severity of NMO. We compared the levels of complement (C3, C4, CH50) and immunoglobulins (IgG, IgM, IgA) between NMO patients and controls. Groups with AQP4 antibody positive and negative NMO patients were also compared with controls, respectively, aiming to elaborate on the relationship between complement activation and immunoglobulins. We also compared these indexes together with expanded disability status scale (EDSS) between two different groups in NMO patients and endeavored to figure out their correlations with each other. Complement and immunoglobulins were compared between NMO patients in acute phase and non-acute phase of the disease to find out the level fluctuation of CH50 and other indexes during different stages of NMO. We analyzed NMO patients (n = 88) and controls (n = 44) for IgG, IgM, IgA, other indexes like CH50, C3, C4 have also been explored between the two groups. Furthermore, we investigated whether these antibodies could mediate complement-dependent cytotoxicity. Thus, the NMO patients were split into two groups with or without AQP4 antibody to find out the status of NMO-IgG in the development and severity of the disease. EDSS was used as criteria for the evaluating the seriousness of NMO. Comparison between NMO patients in acute stage and non-acute stage of the disease was also made for a better understanding of the disease. Compared with controls, NMO patients had much higher IgG (13.984 ± 5.981 mg/ml, 11.430 ± 3.254 mg/ml, P < 0.01) but lower CH50 (respectively, 43.55 ± 12.172 U/L, 50.66 ± 12.523 U/L, P < 0.01). While IgG increased in Anti-AQP4 antibody-positive NMO patients, CH50 dropped in this group when compared with AQP4-negative patients. When compared with controls, both of the NMO groups had enhanced IgG and decreased CH50 though only AQP4-positive NMO patients showed significance (IgG 15.004 ± 6.613 mg/ml, 11.430 ± 3.254 mg/ml, P < 0.01) (CH50, respectively, 41.12 ± 12.581U/L, 50.66 ± 12.523 U/L, P < 0.01). C4 was also decreased though without evident significance (0.215 ± 0.118 mg/ml, 0.260 ± 0.133 mg/ml, P = 0.069). Those NMO patients in acute phase (with the course of newly attack of less than 1 month) had increased immunoglobulin (IgG 14.991 ± 6.639 mg/ml, 12.460 ± 4.490 mg/ml) but decreased complement (CH50 42.755 ± 12.403 U/L, 44.743 ± 11.890 U/L) than those who passed the acute phase. There was correlation between IgG and CH50 (R = -0.402, P < 0.01) in NMO patients. Relationship was also found between IgG and EDSS (R = 0.609, P < 0.001), CH50 and EDSS (R = -0.333, P < 0.01). These results indicate that NMO patients had enhanced immunoglobulin in acute phase but decreased complement. The complement was correlated with immunoglobulin. Among the two NMO groups, the complement system was only activated in NMO-IgG positive patients, which might indicate a potential different pathogenetic mechanism in NMO-IgG negative patients. Also, patients' disability of the former group was more serious than their counterparts. Those patients in acute phase obviously had increased immunoglobulin but decreased complement. Thus, we have come to the conclusion that in AQP4-positive NMO patients, immunoglobulin activates complement system, which influences the functions of NMO patients.