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

Objetivos: 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 pacientescom artrite reumatoide (AR) iniciando tratamento com rituximabe (RTX) com a deplec¸ão etempo de repopulac¸ão dessas células.Métodos: Dez pacientes com AR receberam duas infusões de 1 g de RTX com intervalo de14 dias. Análises imunofenotípicas para detecc¸ão de CD55, CD59, CD35 e CD46 nos linfócitosB foram feitas imediatamente antes da primeira infusão. A populac¸ão de linfócitos B foianalisada por meio da expressão de CD19 basal e após um, dois e seis meses após a infusãode RTX e então trimestralmente até a recaída clínica. Deplec¸ão de linfócitos B no sangueperiférico foi definida como expressão de CD19 < 0,005 × 109/l.Resultados: Dez mulheres com mediana de 49 anos e DAS 28 basal de 5,6 foram avali-adas; nove eram soropositivas para o fator reumatoide. Cinco pacientes apresentaramrepopulac¸ão de linfócitos B após dois meses e as outras cinco aos seis meses. Houvecorrelac¸ão entre a expressão basal de CD46 e o tempo de repopulac¸ão (coeficientede correlac¸ão -0,733, p = 0,0016). Tendência semelhante foi observada com CD35, porém semsignificância estatística (coeficiente de correc¸ão 0,522, p = 0,12).Conclusão: Expressão aumentada de CD46 foi preditora de repopulac¸ão mais rápida de lin-fócitos B em pacientes tratados com RTX. Estudos com um número maior de pacientesserão necessários para confirmar a utilidade da expressão basal das PRC como preditora deresposta clínica.Objectives: 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. Methods: Ten patients with RA received two infusions of 1 g 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. Results: Ten women with a median of 49 years and a baseline DAS28 = 5.6 were evalu- ated; 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 corre- lation 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). Conclusion: 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

Incidence of tuberculosis infection in spondyloarthritis patients treated with biological and conventional diseasemodifying anti-rheumatic drugs in an endemic area

Introduction: Registries of spondyloarthritis (SpA) patients’ follow-up provided evidence that tumor necrosis factor inhibitors (TNFi) increase the incidence of active tuberculosis infection (TB). However, most of these registries are from low burden TB areas. Few studies evaluated the safety of biologic agents in TB endemic areas. This study compares the TB incidence rate (TB IR) in anti-TNF-naïve and anti-TNFexperienced subjects with SpA in a high TB incidence setting. Methods: In this retrospective cohort study, medical records from patients attending a SpA clinic during 13 years (2004 to 2016) in a university hospital were reviewed. The TB IR was calculated and expressed as number of events per 105 patients/year; the incidence rate ratio (IRR) associated with the use of TNFi was calculated. Results: A total of 277 patients, 173 anti-TNF-naïve and 104 anti-TNF-experienced subjects, were evaluated; 35.7% (N = 35) of patients who were prescribed an antiTNF drug were diagnosed with latent tuberculosis infection (LTBI). Total follow-up time (person-years) was 1667.8 for anti-TNF-naïve and 394.9 for anti-TNF-experienced patients. TB IR (95% CI) was 299.8 (37.4-562.2) for anti-TNF naïve and 1012.9 (25.3-2000.5) for anti-TNF experienced subjects. The IRR associated with the use of TNFi was 10.4 (2.3- 47.9). Conclusions: In this high TB incidence setting, SpA patients exposed to anti-TNF therapy had a higher incidence of TB compared to anti-TNF-naïve subjects, although the TB incidence in the control group was significant

Correlação entre a expressão celular de proteínas reguladoras do complemento e a resposta clínica de uma coorte de pacientes com artrite reumatoide tratada com rituximabe

OBJETIVOS: Correlacionar o nível de expressão das proteínas reguladoras do complemento (Cregs) CD55, CD59, CD35 e CD46 nos linfócitos B em uma coorte de pacientes com artrite reumatoide (AR) iniciando terapia com rituximabe (RTX) com a depleção e tempo de repopulação destas células no sangue periférico, associando, ainda, o nível de expressão destas proteínas à resposta clínica conforme os critérios do Colégio Americano de Reumatologia (ACR). MÉTODOS: Dez pacientes com AR receberam duas infusões de RTX 1g separadas por intervalo de 14 dias. Análises imunofenotípicas para detecção de CD19, CD55, CD59, CD35 e CD46 foram realizadas pré-infusão e após 1, 2, 6, 12, 18 e 24 meses ou até recaída clínica. Depleção de linfócitos B no sangue periférico foi definida como valor de CD19 menor que 0,005x109/l no total de leucócitos. Resposta ACR20 em 6 meses foi considerada positiva e recaída clínica foi definida como perda dessa resposta. A não obtenção de ACR20 em 6 meses foi considerada falha de resposta ao tratamento. RESULTADOS: Dez mulheres com mediana de 49 anos e DAS28 basal de 5,6; nove delas soropositivas para fator reumatoide foram acompanhadas. Repopulação de linfócitos B ocorreu em 2 meses em cinco pacientes e em 6 meses nas demais. Houve correlação entre o nível de expressão basal de CD46 com o tempo de repopulação (coeficiente de correlação de -0,733, p=0,016). Tendência semelhante foi detectada com CD35, porém sem significância estatística (coeficiente de correlação de -0,522, p=0,12). Não houve associação entre resposta clínica e expressão das proteínas regulatórias do complemento. CONCLUSÕES: Expressão aumentada de CD46 foi preditora de repopulação mais precoce de linfócitos B em pacientes com AR tratados com RTX. Estudos com amostras maiores serão necessários para avaliar associação das demais Cregs.OBJECTIVES: To correlate the level of expression of the complement regulatory proteins (Cregs) CD55, CD59, CD35, and CD46 on B cells from a cohort of 10 patients with rheumatoid arthritis (RA) initiating treatment with rituximab (RTX) with the depletion and time of repopulation of these cells in peripheral blood, additionally correlating the level of expression of these proteins to clinical response according to the criteria of the American College of Rheumatology (ACR). METHODS: Ten patients with RA received two 1g RTX infusions within 14 day intervals. Immunophenotype analyses for CD19, CD55, CD59, CD35 and CD46 were performed before the infusion and at 1, 2, 6, 12, 18 and 24 months or until recurrence. Depletion of B cells on peripheral blood was defined as the CD19 count < 0.005x109/l. ACR20 at 6 months was considered a good clinical response and recurrence was defined as loss of this response. RESULTS: Ten women with median age of 49 years and basal DAS28 of 5.6 were monitored; 9 were seropositive for rheumatoid factor. Repopulation of B cells occurred within 2 months in 5 patients and within 6 months in the remaining women. There was correlation between the basal level of CD46 expression and the time to achieve repopulation (correlation coefficient -0.733, p=0.016). A similar trend was observed with the CD35, but without statistical significance (correlation coefficient - 0.522, p=012). There was no association between clinical response and the complement regulatory proteins. CONCLUSIONS: Increased CD46 expression predicted earlier repopulation of B cells in RA patients treated with RTX. Studies with larger samples are necessary to assess the association with the other Cregs

Correlação entre a expressão celular de proteínas reguladoras do complemento e a resposta clínica de uma coorte de pacientes com artrite reumatoide tratada com rituximabe

OBJETIVOS: Correlacionar o nível de expressão das proteínas reguladoras do complemento (Cregs) CD55, CD59, CD35 e CD46 nos linfócitos B em uma coorte de pacientes com artrite reumatoide (AR) iniciando terapia com rituximabe (RTX) com a depleção e tempo de repopulação destas células no sangue periférico, associando, ainda, o nível de expressão destas proteínas à resposta clínica conforme os critérios do Colégio Americano de Reumatologia (ACR). MÉTODOS: Dez pacientes com AR receberam duas infusões de RTX 1g separadas por intervalo de 14 dias. Análises imunofenotípicas para detecção de CD19, CD55, CD59, CD35 e CD46 foram realizadas pré-infusão e após 1, 2, 6, 12, 18 e 24 meses ou até recaída clínica. Depleção de linfócitos B no sangue periférico foi definida como valor de CD19 menor que 0,005x109/l no total de leucócitos. Resposta ACR20 em 6 meses foi considerada positiva e recaída clínica foi definida como perda dessa resposta. A não obtenção de ACR20 em 6 meses foi considerada falha de resposta ao tratamento. RESULTADOS: Dez mulheres com mediana de 49 anos e DAS28 basal de 5,6; nove delas soropositivas para fator reumatoide foram acompanhadas. Repopulação de linfócitos B ocorreu em 2 meses em cinco pacientes e em 6 meses nas demais. Houve correlação entre o nível de expressão basal de CD46 com o tempo de repopulação (coeficiente de correlação de -0,733, p=0,016). Tendência semelhante foi detectada com CD35, porém sem significância estatística (coeficiente de correlação de -0,522, p=0,12). Não houve associação entre resposta clínica e expressão das proteínas regulatórias do complemento. CONCLUSÕES: Expressão aumentada de CD46 foi preditora de repopulação mais precoce de linfócitos B em pacientes com AR tratados com RTX. Estudos com amostras maiores serão necessários para avaliar associação das demais Cregs.OBJECTIVES: To correlate the level of expression of the complement regulatory proteins (Cregs) CD55, CD59, CD35, and CD46 on B cells from a cohort of 10 patients with rheumatoid arthritis (RA) initiating treatment with rituximab (RTX) with the depletion and time of repopulation of these cells in peripheral blood, additionally correlating the level of expression of these proteins to clinical response according to the criteria of the American College of Rheumatology (ACR). METHODS: Ten patients with RA received two 1g RTX infusions within 14 day intervals. Immunophenotype analyses for CD19, CD55, CD59, CD35 and CD46 were performed before the infusion and at 1, 2, 6, 12, 18 and 24 months or until recurrence. Depletion of B cells on peripheral blood was defined as the CD19 count < 0.005x109/l. ACR20 at 6 months was considered a good clinical response and recurrence was defined as loss of this response. RESULTS: Ten women with median age of 49 years and basal DAS28 of 5.6 were monitored; 9 were seropositive for rheumatoid factor. Repopulation of B cells occurred within 2 months in 5 patients and within 6 months in the remaining women. There was correlation between the basal level of CD46 expression and the time to achieve repopulation (correlation coefficient -0.733, p=0.016). A similar trend was observed with the CD35, but without statistical significance (correlation coefficient - 0.522, p=012). There was no association between clinical response and the complement regulatory proteins. CONCLUSIONS: Increased CD46 expression predicted earlier repopulation of B cells in RA patients treated with RTX. Studies with larger samples are necessary to assess the association with the other Cregs

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

Objetivos: 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 pacientescom artrite reumatoide (AR) iniciando tratamento com rituximabe (RTX) com a deplec¸ão etempo de repopulac¸ão dessas células.Métodos: Dez pacientes com AR receberam duas infusões de 1 g de RTX com intervalo de14 dias. Análises imunofenotípicas para detecc¸ão de CD55, CD59, CD35 e CD46 nos linfócitosB foram feitas imediatamente antes da primeira infusão. A populac¸ão de linfócitos B foianalisada por meio da expressão de CD19 basal e após um, dois e seis meses após a infusãode RTX e então trimestralmente até a recaída clínica. Deplec¸ão de linfócitos B no sangueperiférico foi definida como expressão de CD19 < 0,005 × 109/l.Resultados: Dez mulheres com mediana de 49 anos e DAS 28 basal de 5,6 foram avali-adas; nove eram soropositivas para o fator reumatoide. Cinco pacientes apresentaramrepopulac¸ão de linfócitos B após dois meses e as outras cinco aos seis meses. Houvecorrelac¸ão entre a expressão basal de CD46 e o tempo de repopulac¸ão (coeficientede correlac¸ão -0,733, p = 0,0016). Tendência semelhante foi observada com CD35, porém semsignificância estatística (coeficiente de correc¸ão 0,522, p = 0,12).Conclusão: Expressão aumentada de CD46 foi preditora de repopulac¸ão mais rápida de lin-fócitos B em pacientes tratados com RTX. Estudos com um número maior de pacientesserão necessários para confirmar a utilidade da expressão basal das PRC como preditora deresposta clínica.Objectives: 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. Methods: Ten patients with RA received two infusions of 1 g 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. Results: Ten women with a median of 49 years and a baseline DAS28 = 5.6 were evalu- ated; 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 corre- lation 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). Conclusion: 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

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

Abstract Objectives: 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. Methods: Ten patients with RA received two infusions of 1 g 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. Results: 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). Conclusion: 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