Restoration of regulatory B cell deficiency following alemtuzumab therapy in patients with relapsing multiple sclerosis
Autor: | Jae Won Hyun, Su Hyun Kim, Ye-Seul Kim, Gayoung Kim, Ho Jin Kim, Eun Jig Lee, Hyun June Shin |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Adult
Male medicine.medical_specialty Time Factors Regulatory B cells Immunology medicine.disease_cause Gastroenterology Peripheral blood mononuclear cell lcsh:RC346-429 CD19 B7-H1 Antigen Autoimmunity Multiple sclerosis 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Antineoplastic Agents Immunological Multiple Sclerosis Relapsing-Remitting Antigens CD Internal medicine medicine Humans Longitudinal Studies Relapse Alemtuzumab lcsh:Neurology. Diseases of the nervous system B cell Analysis of Variance B-Lymphocytes Regulatory biology business.industry General Neuroscience Research medicine.disease Flow Cytometry medicine.anatomical_structure Neurology Mechanism of action biology.protein Female medicine.symptom business 030217 neurology & neurosurgery 030215 immunology medicine.drug |
Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 15, Iss 1, Pp 1-10 (2018) |
ISSN: | 1742-2094 |
Popis: | Background Regulatory B cells (Bregs), which protect from autoimmunity, are deficient in multiple sclerosis (MS). Novel regulatory B cell subsets CD19+CD24hiCD38hi cells and CD19+PD-L1hi cells, with disparate regulatory mechanisms have been defined. Alemtuzumab provides a long-lasting suppression of disease activity in MS. In contrast to its documented efficacy, alemtuzumab’s mechanism of action is not fully understood and information about the composition of repopulating B cell pool is scarce. Aim To characterize repopulated B cell subsets and elucidate alemtuzumab’s mechanism of action in B cell perspective. Methods The frequency and the absolute number of Bregs were studied in peripheral blood mononuclear cells (PBMC) of 37 MS patients and 11 healthy controls (HC). Longitudinal analysis of the frequency and the absolute number of Bregs in PBMC of 11 MS patients was evaluated, before and at 6, 9, and 12 months post alemtuzumab. Results We found deficiency of CD19+CD24hiCD38hi cells during relapse compared to remission and HC (relapse vs remission: p = 0.0006, relapse vs HC: p = 0.0004). CD19+PD-L1hi cells were deficient during relapse than remission and HC (relapse vs remission: p = 0.0113, relapse vs HC: p = 0.0007). Following alemtuzumab, the distribution of B cells shifts towards naïve phenotype and Breg deficiency is restored. The frequency of CD19+CD24hiCD38hi cells was significantly increased at 6 M and 9 M compared to 0 M (6 M vs 0 M: p = 0.0004, 9 M vs 0 M: p = 0.0079). At 9 M, the frequency of CD19+CD24hiCD38hi cells started to decrease and by 12 M the frequency was reduced compared to 6 M, although it was significantly higher than baseline level (12 M vs 0 M: p = 0.0257). The absolute number was significantly increased at 6 M and 9 M post-alemtuzumab (6 M vs 0 M: p = 0.0063, 9 M vs 0 M: p = 0.02). The frequency of CD19+PD-L1hi cells significantly increased until 12 M (6 M vs 0 M: p = 0.0004, 12 M vs 0 M: p = 0.0036). The frequency of CD19+PD-L1hi cells at 12 M was significantly higher than 9 M (p = 0.0311). We further pinpoint that CD19+CD24hiCD38hi cells were deficient at severe relapses following alemtuzumab infusion and restored during recovery. Conclusions Our results highlight the preferential reconstitution of Bregs as a possible mechanism of action of alemtuzumab and CD19+CD24hiCD38hi cells as a potential biomarker for disease activity. |
Databáze: | OpenAIRE |
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