B-179 Mass Spectrometry-based oligoclonal banding has high sensitivity and specificity for multiple sclerosis diagnosis

Background Analysis of cerebrospinal fluid (CSF) is crucial in the diagnostic workup for various neurological disorders, including multiple sclerosis (MS). The presence of CSF-restricted oligoclonal immunoglobulin (IgG) bands (OCB) is an important laboratory marker for the diagnosis of MS. In recent years, kappa free light chain (kFLC) in CSF and the kappa index (K index) have been gaining acceptance as diagnostic biomarkers in MS, and the K index has demonstrated equivalent performance with CSF OCB in many clinical studies. Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-ToF) mass spectrometry methodologies have been increasingly used in the detection of monoclonal immunoglobulins and is currently limited to the diagnosis and management of monoclonal gammopathies. This study aimed to assess the ability of the EXENT system (The Binding Site [TBS], part of Thermo Fisher Scientific) to detect oligoclonal peaks in paired serum and CSF samples with MALDI-ToF mass spectrometry, and to evaluate the clinical performance of mass spectrometry-based OCB compared to traditional OCB testing and K index for the diagnosis of MS. Methods Paired CSF and serum samples from 20 multiple sclerosis (MS) patients (comprising 16 with relapsing-remitting MS (RRMS), 2 with secondary progressive MS (SPMS), and 2 with primary progressive MS (PPMS)) and 20 non-MS patients (including 8 with non-MS inflammatory neurological diseases (NMS-IND), 8 with non-inflammatory neurological diseases (NIND), and 4 neurologically normal (NN)) were analyzed using the EXENT System and by isoelectric focusing. In addition, kFLC and albumin concentrations were determined with the Optilite Freelite Kappa Mx kit and the Optilite Low Level Albumin kit (TBS), and the K index was calculated. Oligoclonal banding was deemed positive when =2 unique IgG CSF bands were present (pattern type 2 and 3), whereas pattern type 1 and 4 were categorized as negative. In the case of mass spectrometry, 4 samples presented with single bands limited to the CSF, which were characterized as type 1. Results The overall diagnostic sensitivity of MALDI-ToF mass spectrometry OCB was 90% with a specificity of 95%, compared to the 95% sensitivity and 85% specificity of traditional OCBs and the 95% sensitivity and 78% specificity of the K index. The positive and negative agreement between MALDI-ToF and the other two methods was high with a positive agreement of 82% and 78% for OCB and K index, respectively, and negative agreement of 100% for both. The accuracy of pattern typing of IgG by MALDI-ToF compared to traditional OCB testing was higher for pattern types 1 and 2 compared to types 3 and 4. However, the overall outcome of diagnosis was accurate in 100% of clinically negative and 74% of clinically positive samples. Conclusion These results demonstrate that MALDI-ToF mass spectrometry may offer a potential sensitive method for the aid in diagnosis of MS and can demonstrate similar clinical performance to current state-of-the-art diagnostic methodologies and assessing OCB in CSF with MALDI-ToF mass spectrometry may be a suitable alternative to isoelectric focusing.