Abstract
Although the detailed pathogenesis of multiple sclerosis (MS) is not completely understood, a broad range of disease-modifying therapies (DMTs) are available. A common side effect of nearly every MS therapeutic agent is lymphopenia, which can be both beneficial and, in some cases, treatment-limiting. A sound knowledge of the underlying mechanism of action of the selected agent is required in order to understand treatment-associated changes in white blood cell counts, as well as monitoring consequences. This review is a comprehensive summary of the currently available DMTs with regard to their effects on lymphocyte count. In the first part, we describe important general information about the role of lymphocytes in the course of MS and the essentials of lymphopenic states. In the second part, we introduce the different DMTs according to their underlying mechanism of action, summarizing recommendations for lymphocyte monitoring and definitions of lymphocyte thresholds for different therapeutic regimens.
Highlights
As more treatment options emerge that have a significant impact on the peripheral immune system, the evaluation of lymphocyte count, and that of specific lymphocyte subsets, become more important in the treatment selection and management of patients with multiple sclerosis (MS) [1,2]
We introduce the different disease-modifying therapies (DMTs) according to their underlying mechanism of action, summarizing recommendations for lymphocyte monitoring and definitions of lymphocyte thresholds for different therapeutic regimens
Current DMTs in MS are often associated with changes in peripheral lymphocyte count
Summary
As more treatment options emerge that have a significant impact on the peripheral immune system, the evaluation of lymphocyte count, and that of specific lymphocyte subsets, become more important in the treatment selection and management of patients with multiple sclerosis (MS) [1,2]. Pharmacological effects on lymphocytes in the peripheral blood can serve as markers of patient compliance and can assist in understanding the mechanism of action of MS therapies [4,5]. Lymphocytes circulating in the peripheral blood represent only about 2% of the total Lymphoncyutmesbceirrcouflalytimngpihnotchyetepseirnipthheerablobdloyoodfryepourensgenatdounlltys.abInoubtl2o%odo,fTthleymtotpahlocytes make number of lyumppmhoocsytte(6s0i–n80th%e)boofdtyheoftoytoaul pngeraipdhueltrsa.lIlnymblpohoodc, yTtelycmoupnhto,cwytieths mthaekreesutpcomprising B most (60–80%ly) mofpthhoectyotteasl apnerdipnhaeturarlallykmillpehro(NcyKte) ccoelulsnt[,1w0]i.thInthpehyresisotlcoogmicpalricsiirncgumB slytamn-ces where the phocytes andpnraotluifrearlaktiiollnerof(NlyKm)pcehlolscy[1te0s].iInntphehybslioooldogiiscvalercyirclouwm,stthaenicrensuwmhbeerredtheepepnrdo-s on their exit liferation of lyfrmopmhoancydteesnitnrythinetbolothode bislovoedry, tlogwe,tthheerirwniuthmtbheerirdterpaennsditstohnrotuhgeihr edxififtefreonmt organs. This and entry intosituhaetbiolonoids ,ctoomgeptlhiceartewditbhyththeeirftarcatntshiat tthlyrmoupghhodcyiftfeesr,elnikteogrgranus.loTchyistessi,thuav- e a marginal tion is complipcoaoteldthbayt itsheinfadcytntahmaticlyemxcphhaoncgyetews,itlhiktehgerpaenruiplohceyrtaels,bhloaovde laymparhgoicnyatlepso[1o1l ]. When starting an immunodepletive therapy, latent virus or mycobacterial infections should be ruled out, and vaccination should be considered
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