Can serum C3/C4 complement ratio be used in the differential diagnosis of central nervous system demyelinating diseases?

Abstract

Background

Neuromyelitis Optica Spectrum Disorders (NMOSD) and Multiple Sclerosis (MS) are primary demyelinating diseases of the central nervous system (CNS) with similar clinical features, complicating early differential diagnosis and treatment decisions. While both humoral and cellular immunity contribute to their immunopathogenesis, the complement system's role remains unclear. We considered complement-dependent cytotoxicity might have different roles in the pathophysiology of these diseases. Predictive value of C3 and C4 complement levels at the first attack for the definitive diagnosis aimed to be investigated.

Methods

Treatment-naive, 14 seronegative (SN) NMO, 28 aquaporin-4-positive [AQP4(+)] NMO, 23 myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and 15 MS adult patients were included. Serum C3 and C4 levels were evaluated retrospectively. Complement levels were statistically adjusted according to the age of the patients and C3/C4 ratio was used to increase statistical power.

Results

We found that C4 levels were lower and C3/C4 ratio was higher in SNNMO and AQP4(+)-NMO groups compared to the MS group. It has been determined that 5.32 and 4.85 cut-off values of the C3/C4 ratio can discriminate SNNMO and AQP4(+)-NMO groups from MS.

Conclusion

The classical complement pathway in SNNMO and AQP4(+)-NMO was thought to be more affected compared to MS, as activation of the classical pathway predominantly decreases the level of C4. Since the involvement of the complement system pathways at different levels may be presented with the C3/C4 ratio, it seems likely that this ratio may have value as a candidate biomarker in the differential diagnosis of primary CNS demyelinating diseases.