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
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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