The Role of C3 and C4 Complement Levels in the Differential Diagnosis of Central Nervous System Demyelinating Diseases
Melike Çakan1, Barışcan Çimen2, Nazire Acar Ozen1, Rana Karabudak1, Asli Tuncer1
1Hacettepe University Faculty of Medicine Department of Neurology, 2Hacettepe University Faculty of Medicine Department of Medical Pharmacology
Objective:

Predictive value of C3 and C4 complement levels at the time of the first attack for the definitive diagnosis aimed to be investigated.

Background:
Neuromyelitis Optica Spectrum Disorders (NMOSD) and Multiple Sclerosis (MS) are primary inflammatory demyelinating diseases of the central nervous system. Since they have similar clinical features, difficulties are experienced in the differential diagnosis and, accordingly, in the early decision for the appropriate treatment. It is thought that NMOSD is humoral immunity mediated and MS is T-lymphocyte-mediated. Seronegative and aquaporin-4 positive (AQP4-IgG+) groups are included in NMOSD and it is considered that complement-dependent cytotoxicity has different roles in the pathophysiology of these sub-groups. 
Design/Methods:
Peripheral blood samples were obtained from naive patients. 14 Seronegative NMO, 28 AQP4-IgG+ NMO, 23 MOGAD and 15 MS patients were included. Serum C3 and C4 levels were evaluated retrospectively. 
Results:
The mean age of the sample was 42±15 and the female ratio was 68.7%. While there was no difference in C3 levels in NMOSD and MS groups, it was determined that C4 levels were lower in NMOSD compared to MS (respectively p values 0.21; 0.035). C4 levels were lower in seronegative and AQP4-IgG+ NMO groups compared to MS (respectively p values 0.026; 0.035).  It has been determined that 4.8 cut-off value for C3/C4 ratio can discriminate MS and NMOSD groups with 67% sensitivity and 70% specificity (AUC:0.786; p=0.002). 
Conclusions:
While activation of the classical pathway more predominantly decreases the level of C4, alternative pathway decreases the level of C3. The classical pathway in NMOSD was thought to be more affected when compared with MS. Since the involvement of the pathways in the complement system at different levels may be presented with the C3/C4 ratio, it seems likely that this ratio may have value as a candidate marker in the differential diagnosis of neurodemyelinating diseases. 
10.1212/WNL.0000000000203464