engleski

Monocyte CD192 as a promising subclinical marker in relapsing-remitting multiple sclerosis: TMS and immunological study

Background: The primary pathological event in multiple sclerosis (MS) is demyelination with degeneration and loss of axons, which correlates with a permanent functional deficit. Monocytes, together with Th1 and Th17 cells, play a key role in CNS inflammation in MS. Gjelstrup et al. [1] showed a decreased expression of CD40 and CD192 markers in the total monocyte population in people with MS compared to the control group. Further, recent findings suggest an association between the pathophysiological mechanisms of MS (demyelination and loss of axons) and TMS neurophysiological measures [2-4]. Objective: To investigate CD40+ and CD192+ blood monocyte subpopulations in relapsing-remitting MS subjects undergoing TMS assessment of corticospinal tract integrity by recording MEPs from upper and lower extremity muscles. The CD40+ and CD192+ blood monocyte subpopulations were compared to healthy controls and MS subjects having prolonged latency of MEPs and subjects having neat MEP findings. Methods: Blood samples needed for flow cytometry were collected from 23 MS subjects and 10 healthy controls and incubated with anti-human-CD14 FITC antibodies, of phycoerythrin-conjugated antibodies reactive to human CD16, mouse antibodies reactive to human CD192 conjugated with BB700 and Alexa Flour 647 conjugated antibodies reactive to human CD40. Results: All MS subjects and MS subjects with prolonged MEP latency differed from the healthy controls in the percentage of CD192 in non- classical anti-inflammatory CD14+CD16++ monocytes, expression of CD40 in CD14++CD16-, percentage of total monocytes positive for CD40, and expression of CD192 in classical CD14++CD16-. MS subjects with prolonged MEP latency differed from MS subjects with neat MEP finding in the expression of CD40 in CD14++CD16- and the percentage of total monocytes positive for CD40.The percentage of CD192 in anti-inflammatory CD14+CD16++ monocytes correlated with the intensity of stimulation used to elicit MEP responses from lower extremity muscles. Conclusions: Distinct results were found concerning the percentage of CD192+ non-classical monocytes and expression of CD192 in classical monocytes when comparing MS subjects with altered MEP latency and those with neat MEP findings. Study results point to the subclinical relevance of CD192+ monocyte subpopulations in MS. The study represents the first attempt to apply TMS in evaluating corticospinal tract integrity with the immunological investigation of MS. References [1] Gjelstrup MC, Stilund M, Petersen T, i sur. Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis. Immunology & Cell Biology 2018 ; 96(2):160-174. doi: 10.1111/imcb.1025 [2] Chalah MA, Palm U, Ayache SS. Editorial: Corticospinal Excitability in Patients With Multiple Sclerosis. Frontiers in Neurology 2021 ; 11: 635612. doi: 10.3389/fneur.2020.635612 [3] Neva JL, Lakhani B, Brown KE, i sur. Multiple measures of corticospinal excitability are associated with clinical features of multiple sclerosis. Behavioral Brain Reserach 2016 ; 297:187-95. doi: 10.1016/j.bbr.2015.10.015 [4] Stampanoni Bassi M, Buttari F, Gilio L, i sur. Inflammation and Corticospinal Functioning in Multiple Sclerosis: A TMS Perspective. Front Neurol 2020 ; 11:566. doi: 10.3389/fneur.2020.00566

multiple sclerosis ; TMS, immunology ; monocytes

In the abstract book: page 44, A-117