Correlation between cellular expression of complement regulatory proteins with depletion and repopulation of B-lymphocytes in peripheral blood of patients with rheumatoid arthritis treated with rituximab

• Published in: Revista Brasileira de Reumatologia Vol. 57; no. 5; pp. 385 - 391
• Main Authors: Viecceli, Daniela, Garcia, Mariana Pires, Schneider, Laiana, Alegretti, Ana Paula, Silva, Cristiano Kohler, Ribeiro, André Lucas, Brenol, Claiton Viegas, Xavier, Ricardo Machado
• Format: Journal Article
• Language: English; Portuguese
• Published: Brazil Elsevier Editora Ltda 01.09.2017; Sociedade Brasileira de Reumatologia
• Subjects: Adult; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Artrite reumatoide; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Biomarcadores; Biomarkers; Biomarkers - blood; Complement regulatory proteins; Drug Administration Schedule; Female; GPI-Linked Proteins - blood; Humans; Infusions, Intravenous; Middle Aged; Proteínas reguladoras do complemento; Rheumatoid arthritis; Rituximab; Rituximab - pharmacology; Rituximab - therapeutic use; Rituximabe; Treatment Outcome; Rheumatoid arthritis; Rituximab; Biomarkers; Complement regulatory proteins; Rituximabe; Proteínas reguladoras do complemento; Biomarcadores; Artrite reumatoide
• ISSN: 2255-5021; 1809-4570; 2255-5021
• DOI: 10.1016/j.rbre.2016.09.007

To correlate the basal expression of complement regulatory proteins (CRPs) CD55, CD59, CD35, and CD46 in B-lymphocytes from the peripheral blood of a cohort of 10 patients with rheumatoid arthritis (RA) initiating treatment with rituximab (RTX) with depletion and time repopulation of such cells. Ten patients with RA received two infusions of 1g of RTX with an interval of 14 days. Immunophenotypic analysis for the detection of CD55, CD59, CD35, and CD46 on B-lymphocytes was carried out immediately before the first infusion. The population of B-lymphocytes was analyzed by means of basal CD19 expression and after 1, 2, and 6 months after the infusion of RTX, and then quarterly until clinical relapse. Depletion of B-lymphocytes in peripheral blood was defined as a CD19 expression <0.005×109/L. Ten women with a median of 49 years and a baseline DAS28=5.6 were evaluated; 9 were seropositive for rheumatoid factor. Five patients showed a repopulation of B-lymphocytes after 2 months, and the other five after 6 months. There was a correlation between the basal expression of CD46 and the time of repopulation (correlation coefficient=−0.733, p=0.0016). A similar trend was observed with CD35, but without statistical significance (correction coefficient=−0.522, p=0.12). The increased CD46 expression was predictive of a faster repopulation of B-lymphocytes in patients treated with RTX. Studies involving a larger number of patients will be needed to confirm the utility of basal expression of CRPs as a predictor of clinical response. Correlacionar a expressão basal das proteínas reguladoras do complemento (PRC) CD55, CD59, CD35 e CD46 nos linfócitos B do sangue periférico de uma coorte de 10 pacientes com artrite reumatoide (AR) iniciando tratamento com rituximabe (RTX) com a depleção e tempo de repopulação dessas células. Dez pacientes com AR receberam duas infusões de 1g de RTX com intervalo de 14 dias. Análises imunofenotípicas para detecção de CD55, CD59, CD35 e CD46 nos linfócitos B foram feitas imediatamente antes da primeira infusão. A população de linfócitos B foi analisada por meio da expressão de CD19 basal e após um, dois e seis meses após a infusão de RTX e então trimestralmente até a recaída clínica. Depleção de linfócitos B no sangue periférico foi definida como expressão de CD19<0,005×109/l. Dez mulheres com mediana de 49 anos e DAS 28 basal de 5,6 foram avaliadas; nove eram soropositivas para o fator reumatoide. Cinco pacientes apresentaram repopulação de linfócitos B após dois meses e as outras cinco aos seis meses. Houve correlação entre a expressão basal de CD46 e o tempo de repopulação (coeficiente de correlação -0,733, p=0,0016). Tendência semelhante foi observada com CD35, porém sem significância estatística (coeficiente de correção 0,522, p=0,12). Expressão aumentada de CD46 foi preditora de repopulação mais rápida de linfócitos B em pacientes tratados com RTX. Estudos com um número maior de pacientes serão necessários para confirmar a utilidade da expressão basal das PRC como preditora de resposta clínica.