2026-04-17T03:26:33Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/74902024-06-06T14:03:15Zcom_2072_378070com_2072_378040com_2072_378071col_2072_378092col_2072_378097

Role of B Cell Profile for Predicting Secondary Autoimmunity in Patients Treated With Alemtuzumab Walo-Delgado, Paulette Esperanza Medina, Silvia Quintana, Ester Fernández-Velasco, José Ignacio Montalban Gairín, Xavier Midaglia Fernandez, Luciana Sainz de la Maza, Susana Comabella Lopez, Manuel Monreal, Enric Esclerosi múltiple - Tractament Cèl·lules B Autoimmunitat DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis::Multiple Sclerosis, Relapsing-Remitting Other subheadings::Other subheadings::Other subheadings::/drug therapy ANATOMY::Cells::Antibody-Producing Cells::B-Lymphocytes ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple::esclerosis múltiple recurrente-remitente Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia ANATOMÍA::células::células productoras de anticuerpos::linfocitos B Células B; Alemtuzumab; Autoinmunidad Limfòcits B; Alemtuzumab; Autoimmunitat B cells; Alemtuzumab; Autoimmunity Objective: To 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. Methods: Multicenter 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. Results: Twenty-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). Conclusions: A PB/PC percentage <0.1% at baseline identifies MS patients at low risk of secondary autoimmunity during alemtuzumab treatment.​ This work was supported by grants from Red Española de Esclerosis Múltiple (REEM) (RD16/0015/0001; RD16/0015/0004; RD16/0015/0006; RD16/0015/0013) and PI18/00572 integrated in the Plan Estatal I+D+I and co-funded by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER, “Una manera de hacer Europa”). 2022-05-06T12:35:00Z 2022-05-06T12:35:00Z 2021-10 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Frontiers in Immunology;12 https://doi.org/10.3389/fimmu.2021.760546 info:eu-repo/grantAgreement/ES/PE2013-2016/RD16%2F0015%2F0004 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Frontiers Media Scientia