Changes in lymphocytes, neutrophils and immunoglobulins in year-1 cladribine treatment in multiple sclerosis

Abstract

Cladribine is a synthetic purine nucleoside analogue, approved for the treatment of active multiple sclerosis (MS). Cladribine mechanism-of-action encompasses selective cytotoxicity on circulating autoreactive B and T lymphocytes, which are thought to drive inflammatory demyelination and neuro-axonal loss in MS ( Compston and Coles, 2008 Compston A. Coles A. Multiple sclerosis. Lancet. 2008; 372: 1502-1517https://doi.org/10.1016/S0140-6736(08)61620-7 Abstract Full Text Full Text PDF PubMed Scopus (3270) Google Scholar ). Looking at clinical trial results, during cladribine treatment, there is a marked and long-lasting CD19 B-cell depletion and a rather modest T-cell depletion ( Baker et al., 2017 Baker D. Herrod S.S. Alvarez-Gonzalez C. et al. Both cladribine and alemtuzumab may effect MS via B-cell depletion. Neurol. Neuroimmunol. NeuroInflamm. 2017; 4: e360 Crossref PubMed Scopus (71) Google Scholar ; Stuve et al., 2019 Stuve O. Soerensen P. Leist T. et al. Effects of cladribine tablets on lymphocyte subsets in patients with multiple sclerosis: an extended analysis of surface markers. Ther. Adv. Neurol. Disord. 2019; 12: 1-6 Crossref Scopus (40) Google Scholar ; Comi et al., 2019 Comi G. Cook S. Giovannoni G. et al. Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis. Mult. Scler. Relat. Disord. 2019; 29: 168-174 Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar ). Ideally, cladribine only targets memory B cells ( Moser et al., 2020 Moser T. Schwenker K. Seiberl M. et al. Long-term peripheral immune cell profiling reveals further targets of oral cladribine in MS. Ann. Clin. Transl. Neurol. 2020; 7: 2199-2212 Crossref PubMed Scopus (14) Google Scholar ), while plasma cells should remain unaffected ( Jacobs et al., 2018 Jacobs B.M. Ammoscato F. Giovannoni G. et al. Cladribine: mechanisms and mysteries in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 2018; 89: 1266-1271 Crossref PubMed Scopus (25) Google Scholar ), with normal immunoglobulin (Ig) levels, though never explored.