Role of B Cell Profile for Predicting Secondary Autoimmunity in Patients Treated With Alemtuzumab

Abstract

ObjectiveTo explore if baseline blood lymphocyte profile could identify relapsing remitting multiple sclerosis (RRMS) patients at higher risk of developing secondary autoimmune adverse events (AIAEs) after alemtuzumab treatment.MethodsMulticenter prospective study including 57 RRMS patients treated with alemtuzumab followed for 3.25 [3.5-4.21] years, (median [interquartile range]). Blood samples were collected at baseline, and leukocyte subsets determined by flow cytometry. We had additional samples one year after the first cycle of alemtuzumab treatment in 39 cases.ResultsTwenty-two patients (38.6%) developed AIAEs during follow-up. They had higher B-cell percentages at baseline (p=0.0014), being differences mainly due to plasmablasts/plasma cells (PB/PC, p=0.0011). Those with no AIAEs had higher percentages of CD4+ T cells (p=0.013), mainly due to terminally differentiated (TD) (p=0.034) and effector memory (EM) (p=0.031) phenotypes. AIAEs- patients also showed higher values of TNF-alpha-producing CD8+ T cells (p=0.029). The percentage of PB/PC was the best variable to differentiate both groups of patients. Baseline values >0.10% closely associated with higher AIAE risk (Odds ratio [OR]: 5.91, 95% CI: 1.83-19.10, p=0.004). When excluding the 12 patients with natalizumab, which decreases blood PB/PC percentages, being the last treatment before alemtuzumab, baseline PB/PC >0.1% even predicted more accurately the risk of AIAEs (OR: 11.67, 95% CI: 2.62-51.89, p=0.0007). The AIAEs+ group continued having high percentages of PB/PC after a year of alemtuzumab treatment (p=0.0058).ConclusionsA PB/PC percentage <0.1% at baseline identifies MS patients at low risk of secondary autoimmunity during alemtuzumab treatment.​

XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (II)

“…La implementación de ciertos biomarcadores permitirá una medicina cada vez más personalizada. Un estudio de seguimiento prospectivo en EM remitente-recurrente ha mostrado que, en pacientes con características demográficas y clínicas similares, los porcentajes bajos de linfocitos B CD19 + en la sangre o plasmoblastos antes de iniciar tratamiento con alemtuzumab predijeron un menor riesgo de acontecimientos adversos autoinmunitarios [28].…”

Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation

“…Multiple sclerosis is a highly heterogenous severe autoimmune neurodegenerative disorder with an evident inflammation component (1). Despite considerable advances in this field, the mechanism triggering it remains elusive, hindering the development of effective therapeutics (2)(3)(4)(5)(6)(7)(8). MS progression is mostly associated with the promotion of the T cell response (9,10).…”