Analysis of the regulatory function of natural killer cells from patients with systemic lupus erythematosus.

Natural killer (NK) cells participate in the regulation of the immune response. However, the immunomodulatory function of NK cells in systemic lupus erythematosus (SLE) is not well understood. The aim of this study was to evaluate the regulatory function of NK cells in SLE patients and to identify the NK cells involved in the pathogenesis of this complex disease. We analysed the expression of NK receptors and co-stimulatory molecules in peripheral NK cells (CD3- CD56+ ) from SLE patients, as well as the numbers of human leucocyte antigen D-related (HLA-DR)/CD11c+ NK cells. In addition, NK cell regulatory function was assessed by the detection of NK cell-mediated dendritic cell (DC) lysis. We found that SLE patients showed increased numbers of immunoglobulin-like transcript 2 (ILT2)+ , CD86+ and CD134+ NK cells. Furthermore, NK cells from SLE patients induced higher levels of DC lysis. We were able to identify a new subset of NK cells co-expressing CD11c and HLA-DR. These atypical NK cells were increased in SLE patients when compared with controls. We have identified an expanded new subset of NK cells in SLE patients. This is the first study, to our knowledge, which demonstrates that NK cells in SLE patients have an altered phenotype with a high expression of receptors characteristic of dendritic cells. Our results suggest that the impairment in the regulatory function of NK cells, together with the increased number of DC-like NK cells, could play an important role in the development of SLE and highlight the importance of NK cells as a future therapeutic target.

Urinary sediment suggests lupus nephritis histology.

Objectives The objective of this paper was to evaluate correlations between kidney biopsy indexes (activity and chronicity) and urinary sediment findings; the secondary objective was to find which components of urinary sediment can discriminate proliferative from other classes of lupus nephritis. Methods Lupus nephritis patients scheduled for a kidney biopsy were included in our study. The morning before the kidney biopsy, we took urine samples from each patient. Receiver operating characteristic (ROC) curves were plotted to determine the area under the curve (AUC) of each test for detecting proliferative lupus nephritis; a classification tree was calculated to select a set of values that best-predicted lupus nephritis classes. Results We included 51 patients, 36 of whom were women (70.6%). Correlations of lupus nephritis activity index with the counts in the urinary sediment of erythrocytes (isomorphic and dysmorphic), acanthocytes, and leukocytes were 0.65 ( p < 0.0001) 0.62 ( p < 0.0001) and 0.22 ( p = 0.1228), respectively. Correlations of lupus nephritis chronicity index with the counts of erythrocytes, acanthocytes, and leukocytes were 0.60 ( p ≤ 0.0001), 0.52 ( p = 0.0001) and 0.17 ( p = 0.2300), respectively. Our classification tree had an accuracy of 84.3%. Conclusions Evaluation of urine sediment reflects lupus nephritis histology.

Frequency of dental caries in active and inactive systemic lupus erythematous patients: salivary and bacterial factors.

OBJECTIVE: The objective of this study was to determine dental caries frequency and to analyze salivary and bacterial factors associated with active and inactive systemic lupus erythematous (SLE) patients. Also, a proposal to identify dental caries by a surface, teeth, and the patient was developed. MATERIAL AND METHODS: A cross-sectional, blinded study that included 60 SLE patients divided into two groups of 30 subjects each, according to the Activity Index for Diagnosis of Systemic Lupus Erythematous (SLEDAI). The decayed, missing, and filled teeth (DMFT) index and Integrative Dental Caries Index (IDCI) were used for analyzing dental caries. The saliva variables recorded were: flow, pH, and buffer capacity. The DNA copies of Streptococcus mutans and Streptococcus sobrinus were estimated by real-time PCR. RESULTS: The caries frequency was 85% for SLE subjects (73.3% for inactive systemic lupus erythematous (ISLE) and 100% for active systemic lupus erythematous (ASLE)); DMFT for the SLE group was 12.6 ± 5.7 and the IDCI was (9.8 ± 5.9). The ASLE group showed a salivary flow of 0.65 compared with 0.97 ml/1 min from the ISLE group; all variables mentioned above showed a statistical difference (p < 0.05). The salivary pH was 4.6 (6.06 for ISLE and 3.9 for ASLE). The DNA copies of S. mutans and S. sobrinus were high; all variables mentioned above show a significant statistical difference (p < 0.05) between groups. CONCLUSION: SLE patients had high DMFT and IDCI scores that were associated with a decrease in salivary flow, pH, and buffer capacity. There were high counts of S. sobrinus and S. mutans species, and IDCI is a useful tool to provide more detail about dental caries in epidemiological studies.

Proportions of several types of plasma and urine microparticles are increased in patients with rheumatoid arthritis with active disease.

We analysed the proportions of different microparticles (MPs) in plasma from patients with rheumatoid arthritis (RA), and assessed their relationship with disease activity/therapy and their in-vitro effect on proinflammatory cytokine release. Blood and urine samples were obtained from 55 patients with RA (24 untreated and 31 under conventional therapy) and 20 healthy subjects. Fourteen patients with systemic lupus erythematosus (SLE) were also studied. The proportions of CD3(+) , CD14(+) , CD19(+) , CD41(+) and CD62E(+) MPs were determined by flow cytometry analysis. The in-vitro effect of plasma MPs on the release of interleukin (IL)-1, IL-6, IL-17 and tumour necrosis factor (TNF)-α was also analysed. We detected that the proportions of different types of annexin-V(+) MPs were enhanced in plasma (CD3(+) , CD14(+) , CD19(+) , CD41(+) and CD62E(+) MPs) and urine (CD14(+) , CD3(+) and CD19(+) MPs) from RA patients with high disease activity (DAS28 index > 5·1). Accordingly, a significant positive correlation was observed between the levels of MPs and DAS28 score, and these levels diminished significantly at week 4 of immunosuppressive therapy. Finally, MPs isolated from patients with high disease activity induced, in vitro, an enhanced release of IL-1, IL-17 and TNF-α. In SLE, enhanced levels of different types of plasma MPs were also detected, with a tight correlation with disease activity. Our data further support that MPs have a relevant role in the pathogenesis of RA and suggest that the analysis of the proportions of these microvesicles in plasma could be useful to monitor disease activity and therapy response in patients with RA.

Cutaneous papillomavirus infection in patients with rheumatoid arthritis or systemic lupus erythematosus. A case-control study.

Previous studies informed an increased prevalence of cutaneous papillomavirus (cHPV) infection in patients with systemic lupus erythematosus (SLE). The main objective of our study was to evaluate factors associated with cHPV infection in patients with either rheumatoid arthritis (RA) or SLE, and to determine whether SLE itself is an independent risk factor for cHPV infection. We included 670 patients (in consecutive selection) in this cross-sectional study (550 with RA and 120 with SLE). All patients were evaluated by a dermatologist; patients with cHPV infection were selected as cases (63) and the other 607 patients were selected as controls. The prevalence of cHPV infection was increased 2.8-fold in SLE patients (20%) compared with RA patients (7.1%). When comparing cases with controls, bivariate analysis showed statistically significant differences for: age, having SLE, and treatment with mycophenolate mofetil (MMF). When all of the potential risk factors identified using bivariate analysis (age, having SLE, and MMF) were included into a multivariate model, independent risk factors for cHPV infection were: having SLE (odds ratio: 2.16, 95% confidence interval: 1.04-4.48) and MMF therapy (odds ratio: 2.91, 95% confidence interval: 1.18-7.14).

Decreased blood levels of B lymphocytes and NK cells in patients with systemic lupus erythematosus (SLE) infected with papillomavirus (HPV).

Patients with systemic lupus erythematosus (SLE) show an enhanced risk to develop human papillomavirus (HPV) infection, and aggressive forms of this condition are seen in these patients. The aim of this study was to assess the possible relationship among HPV infection, immunosuppressive therapy and levels of leukocyte subsets in patients with SLE. The following individuals were included in the study: (1) SLE patients under immunosuppressive therapy and with lesions caused by HPV (n = 16); (2) SLE patients under immunosuppressive therapy and no evidence of HPV infection (n = 20); (3) untreated SLE patients with no evidence of HPV infection (n = 7), and; (4) healthy female subjects without evidence of HPV infection (n = 10). Peripheral blood was obtained and the percentages of different lymphocyte subsets were determined by flow cytometry, with the use of the following monoclonal antibodies: CD3, CD4, CD8, CD16, CD19, CD20, CD22, CD56, and CD335 (NKp46). We found that SLE patients under immunosuppressive therapy and with lesions caused by HPV showed significantly lower levels of B lymphocytes and NK cells compared to other groups. In contrast, SLE patients receiving immunosuppressive drugs and with no evidence of HPV infection showed similar levels of B and NK cells than healthy controls. Those patients receiving mycophenolate mofetil (MMF) had a diminished number of B cells, and a positive correlation was detected between the dose of MMF and the number of HPV skin lesions. Our data suggest that therapy of SLE patients with MMF is associated with diminished levels of B and NK cells and an enhanced risk for HPV infection.

Análisis de la composición corporal en mujeres adultas con lupus eritematoso sistémico / Body composition analysis in adult women with systemic lupus erythematosus

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Recurrent diffuse alveolar haemorrhage in a patient with systemic lupus erythematosus: long-term benefit of rituximab.

Diffuse alveolar haemorrhage (DAH) is an uncommon complication of systemic lupus erythematosus (SLE), and recurrences of DAH with remission periods are unusual. We describe a young woman with cachexia as the initial manifestation of SLE who presented posterior reversible encephalopathy syndrome (PRES), intestinal vasculitis and four episodes of DAH even though she was receiving combined immune suppressive therapy. After treatment with rituximab (RTX) the patient has not presented further episodes of DAH.

Predictors of mortality in diffuse alveolar haemorrhage associated with systemic lupus erythematosus.

The objective of this study was the evaluation of clinical, demographic and treatment-associated mortality factors in patients with diffuse alveolar haemorrhage (DAH) associated with systemic lupus erythematosus (SLE). Clinical, laboratory test, SLEDAI-2K, predictors of mortality (APACHE II) and different treatments including cyclophosphamide, methylprednisolone and rituximab were evaluated in SLE patients who were diagnosed with DAH, to determine potential association with mortality. Twenty-nine episodes of DAH in 22 SLE patients were included (one patient with four episodes, four patients with two episodes (seven recurrences)), 15 died. Mean age was 25.1 years and 1.5 years of SLE evolution with haemoglobin drop 3.4 g/dl. In 4 of 22 patients, the DAH diagnosis was confirmed by autopsy. Six episodes were in patients under 18 years of age (2 patients with recurrence). DAH was the initial manifestation of SLE in 10 patients. Of the 22 patients, 17 were women and 22/29 had DAH episodes. Dyspnoea and nephritis occurred in all patients, less common were arthritis (75.9%) and fever (65.5%); haemoptysis was present only in 44.8%. Through evaluation of all included factors, only thrombocytopenia, renal failure, requirement for mechanical ventilation and high APACHE II were associated with higher mortality. Cyclophosphamide use was associated with less mortality (not statistically significant).

Expression and function of Cbl-b in T cells from patients with systemic lupus erythematosus, and detection of the 2126 A/G Cblb gene polymorphism in the Mexican mestizo population.

Systemic lupus erythematosus (SLE) is characterized by abnormalities in the function of T and B lymphocytes and in the signaling pathways induced through their receptors. Cbl-b is an intracellular adaptor protein that plays a key role in the negative regulation of lymphocyte activity. We explored the expression and function of Cbl-b in T lymphocytes from SLE patients. In addition, the possible association of SLE and a single nucleotide polymorphism (SNP) of the Cblb gene was determined. We studied 150 SLE patients, 163 healthy individuals, and 14 patients with rheumatoid arthritis (RA). The expression of Cbl-b was analyzed in the peripheral blood mononuclear cells, and the negative regulatory function of Cbl-b was assessed by analyzing actin polymerization and the phosphorylation of JNK and c-Jun induced through CD3. Furthermore, the 2126(A/G) SNP of the Cblb gene was detected by real-time polymerase chain reaction. We found a significant small reduction in the expression of Cbl-b as well as increased levels of activation of c-Jun and actin polymerization in T lymphocytes from patients with SLE compared with healthy controls or RA patients. In addition, a significant association between the 2126(A/G) SNP and SLE was detected. Our data suggest that Cbl-b may contribute to the deregulated activation of T lymphocytes observed in SLE.

Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)).

OBJECTIVES: This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. METHODS: Patients with active disease on stable MTX (10-25 mg/week) were randomised to rituximab 2 x 500 mg (n=168), rituximab 2 x 1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) > or =2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2 x 500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. RESULTS: At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2 x 500 mg) + MTX, rituximab (2 x 1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. CONCLUSIONS: Rituximab (at 2 x 500 mg and 2 x 1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.

[Assessment of nutritional status in a Mexican population of adult patients with rheumatoid arthritis]. / Evaluación del estado nutricio en una población mexicana de pacientes adultos con artritis reumatoide.

BACKGROUND: Rheumatoid arthritis (RA) represents a life-long chronic inflammatory process frequently associated to potential multiorganic complications. Cardiovascular diseases and nutritional alterations are increased in AR populations and represent potential factors that alter negatively the disease course and prognosis. PURPOSE: To evaluate nutritional status from a Mexican AR population, including body composition, anthropometrics and dietary patterns. MATERIAL AND METHODS: There were included 100 RA outpatients from a regional rheumatic centre located in San Luis Potosi México. Nutritional assessment included anthropometric evaluation, bioelectrical impedance analysis (BIA) and dietary patterns evaluation. RESULTS: 100 RA out-patients were included. Mean age was 47.6 +/- 13.3 years, with a mean disease course of 10.18 +/- 9.02. 79% of patients were in RA functional class II and 21% in class III. Average body mass index 26.8 +/- 4.4 kg/m2 According to body mass index categories, 65% patients were within the range of overweight and obesity and 2% of patients were undernourished. Mean waist circumference 86.7 +/- 11.1 cm, 34% of patients showed waist circumference values over the limits established for the definition of metabolic syndrome. Lean body mass was diminished in 48% patients. Body fat mass estimated by anthropometry and BIA was increased in 94 patients (94%). DIETARY PARAMETERS: Mean energy intake was 26.4 +/- 8.2 kcal/kg. There was qualitative nutritional inadequacy in 90 patients (90%). Protein intake was optimal in all the patients. CONCLUSION: Nutritional alterations are highly prevalent in Mexican RA population; our study showed freefat mass depletion, low caloric intake, dietary inadequate parameters and fat mass increments as the more prevalent findings. Nutritional assessment and nutritional strategies are recommended as potential measures to improve RA clinical course and prognosis.

Evaluación del estado nutricio en una población mexicana de pacientes adultos con artritis reumatoide / Assessment of nutritional status in a mexican population of adult patients with rheumatoid arthritis

Antecedentes: La artritis reumatoide (AR) representa un estado inflamatorio crónico que se acompaña de potenciales complicaciones a nivel multiorgánico. Se ha descrito una alta prevalencia de alteraciones nutricias en pacientes con AR, las cuales en conjunto, pueden repercutir negativamente en el curso y pronóstico de la enfermedad ya sea a través de un incremento en la incidencia de morbilidades cardiovasculares o bien imponiendo limitaciones funcionales adicionales a las ya existentes por la enfermedad de base. Propósito: Evaluar nutricionalmente en términos de composición corporal y patrón de ingesta dietaria a una población mexicana con diagnóstico de AR. Material y métodos: Se evaluaron 100 pacientes ambulatorios con el diagnóstico de AR que acuden al servicio de consulta externa de un centro regional de reumatología en San Luís Potosí México. Se determinaron las variables antropométricas, composición corporal por análisis de bioimpedancia eléctrica (BIA) y patrones dietarios. Resultados: Se incluyeron un total de 87 (87%) mujeres y 13 (13%) varones. La edad media fue de 47,6 ± 13,3 años, con una evolución promedio de la enfermedad de 10,18 ± 9,02 años. 79% de los pacientes se encontraban en clase funcional II y 21% en clase funcional III. El índice de masa corporal promedio fue de 26,8 ± 4,4 kg/m2 , 65% de los pacientes presentaron índices de masa corporal (IMC) en rango de sobrepeso u obesidad y solo el 2% en rango de desnutrición. 48% de la muestra presentó depleción de masa magra y 94% presentaron incremento en el porcentaje de grasa corporal estimados por BIA y antropometría. 34 pacientes (34%) presentaron circunferencia abdominal por arriba de los puntos de corte para el diagnóstico de síndrome metabólico. En cuanto a las características cualitativas de la dieta el 90% de la muestra consumía una dieta inadecuada, con una ingesta calórica diaria promedio de 26.49 ± 8.24 kcal. por día; la ingesta de proteínas fue óptima en la totalidad de la población. Conclusión: Existe una elevada prevalencia de alteraciones nutricias en la población mexicana con AR, los hallazgos mas frecuentes en este estudio fueron disminución en masa magra, incremento en reserva grasa, ingesta calórica disminuida y dietas cualitativamente inadecuadas. Se requieren estrategias de intervención para el abordaje y tratamiento nutricional de pacientes con AR como medidas potenciales que modifiquen el curso y pronóstico de la enfermedad (AU)

Background: Rheumatoid arthritis (RA) represents a life-long chronic inflammatory process frequently associated to potential multiorganic complications. Cardiovascular diseases and nutritional alterations are increased in AR populations and represent potential factors that alter negatively the disease course and prognosis. Purpose: To evaluate nutritional status from a Mexican AR population, including body composition, anthropometrics and dietary patterns. Material and methods: There were included 100 RA outpatients from a regional rheumatic centre located in San Luis Potosi México. Nutritional assessment included anthropometric evaluation, bioelectrical impedance analysis (BIA) and dietary patterns evaluation. Results: 100 RA out-patients were included. Mean age was 47.6 ± 13.3 years, with a mean disease course of 10.18 ± 9.02. 79% of patients were in RA functional class II and 21% in class III. Average body mass index 26.8 ± 4.4 kg/m2 According to body mass index categories, 65% patients were within the range of overweight and obesity and 2% of patients were undernourished. Mean waist circumference 86.7 ± 11.1 cm, 34% of patients showed waist circumference values over the limits established for the definition of metabolic syndrome. Lean body mass was diminished in 48% patients. Body fat mass estimated by anthropometry and BIA was increased in 94 patients (94%). Dietary parameters: Mean energy intake was 26.4 ± 8.2 kcal/kg. There was qualitative nutritional inadequacy in 90 patients (90%). Protein intake was optimal in all the patients. Conclusion: Nutritional alterations are highly prevalent in Mexican RA population; our study showed freefat mass depletion, low caloric intake, dietary inadequate parameters and fat mass increments as the more prevalent findings. Nutritional assessment and nutritional strategies are recommended as potential measures to improve RA clinical course and prognosis (AU)

Analysis of expression and function of the inhibitory receptor ILT2 (CD85j/LILRB1/LIR-1) in peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE).

The aim of this work was to study the expression and function of the inhibitory receptor ILT2/CD85j in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). We studied 23 SLE patients as well as 17 patients with rheumatoid arthritis, 10 with fibromyalgia, and 23 healthy individuals. We found a variable level of expression of ILT2 in the PBMC from both SLE patients and controls, with no significant differences among them. However, when the expression of this receptor was assessed in cell subsets, significantly lower levels were detected in CD19+ lymphocytes from SLE patients compared with healthy controls. Functional assays performed in unfractionated PBMC, showed a significant diminished inhibitory activity of ILT2 in CD4+ and CD8+ cell subsets from SLE patients compared to either rheumatoid arthritis or fibromyalgia patients, and healthy individuals. Our results show that the PBMC from some patients with SLE show a defective expression of ILT2, and that most of them exhibit a poor function of this inhibitory receptor.

Phenotypic analysis of IL-10-treated, monocyte-derived dendritic cells in patients with systemic lupus erythematosus.

Dendritic cells (DC) play a dual role in the immune response, participating in its induction, and the maintenance of immune tolerance. The aim of this work was to perform a quantitative and phenotypic analysis of DC generated in vitro in the presence of IL-10 in patients with systemic lupus erythematosus (SLE). Blood samples were obtained from 10 active and untreated patients with SLE and six controls. Monocyte-derived DC were generated in vitro in the presence or absence of IL-10, and a quantitative and phenotypic analysis was performed. We found that freshly isolated monocytes from SLE patients had an increased expression of CD11b. On the other hand, the efficiency of in vitro DC generation was diminished in blood samples from SLE patients for conventional DC, but not for IL-10-treated DC. A diminished expression of HLA-DR, CD9 and CD86 was observed in conventional DC from SLE patients compared with controls. In contrast, enhanced levels of HLA-DR, CD80, CD9 and CD151 tetraspanins, FN1 (a class II MHC-tetraspanin epitope), CD85j/ILT2 and CD69 were detected in IL-10-treated DC from SLE patients. Accordingly, the phenotypic profile of IL-10-treated DC was very different in SLE and controls. However, the synthesis of IL-10 and IL-12 was similar in IL-10-treated and conventional cells in both SLE patients and controls. Our findings on the aberrant phenotype of IL-10-treated DC in SLE and their normal efficiency of in vitro generation may be important for the design of future therapies of this condition based on the administration of DC to induce immune tolerance.

Expression and function of IL-10R in mononuclear cells from patients with systemic lupus erythematosus.

OBJECTIVE: To assess the expression and function of the receptor for interleukin-10 (IL-10R) in immune cells from patients with systemic lupus erythematosus (SLE). METHODS: We assessed the expression and function of IL-10R in peripheral blood mononuclear cells (PBMCs) from 19 SLE patients and 15 healthy controls. The expression of IL-10R was assessed by flow cytometry, and the function of this receptor was determined by analysing both the activation of Jak-1, Tyk-2, Stat-1, and Stat-3 (Western blot) and the induction of gene expression (cDNA array test of 242 genes of cytokines, apoptosis and intracellular signalling) upon stimulation with IL-10. RESULTS: We found similar levels of IL-10R expression in SLE patients and controls. In addition, variable levels of Jak-1, Tyk-2, Stat-1, and Stat-3 activation were induced by IL-10 in PBMCs from SLE patients and controls, with no significant differences in protein phosphorylation or kinetics of activation. However, clear-cut differences in the gene expression induced through IL-10R were observed in SLE patients and controls, mainly in the genes involved in apoptosis and those encoding for cytokines and their receptors. CONCLUSIONS: Our data suggest that despite normal levels of IL-10R expression, and an apparent lack of abnormalities in the intracellular signals induced through this receptor, immune cells from SLE patients exhibit an aberrant pattern of gene expression induced through the IL-10R.

Efecto de Rituximab in vivo sobre las células T reguladoras y la apoptosis en pacientes de artritis reumatoide / In vivo effect of Rituximab on regulatory T cells and apoptosis in patients with rheumatoid arthritis

El propósito de este estudio es el de comprobar el efecto in vivo de la terapia de anticuerpos anti-CD20 con Rituximab sobre los linfocitos T reguladores y la apoptosis de células inmunitarias en pacientes con artritis reumatoidea (RA). En un ensayo piloto abierto, se administró Rituximab (1,0 g en los días 1 y 30) a siete pacientes con RA que eran refractarios a la terapia convencional. Se obtuvieron muestras de sangre periférica en los días 0, 15 y 180 de terapia con Rituximab, analizándose el número y funcionalidad de linfocitos T reguladores, así como la presencia de células apoptóticas. Cinco de los siete pacientes mostraron una mejora clínica significativa tras el tratamiento por Rituximab (respuesta ACR 50-70), y también un aumento del número y la función de las células T reguladoras. Además, se detectó un incremento en el porcentaje de células apoptóticas en sangre periférica al inicio de la terapia con Rituximab. Estos datos sugieren que Rituximab ejerce un efecto de interés sobre las células T reguladoras en pacientes con RA, un fenómeno que puede contribuir al efecto terapéutico de este anticuerpo anti-CD20 en RA

The aim of this study was to assess the in vivo effect of anti- CD20 therapy with Rituximab on regulatory T lymphocytes, and apoptosis of immune cells in patients with rheumatoid arthritis (RA). In an open and pilot clinical trial, Rituximab was administered (1.0 g at days 1 and 30) to seven patients with RA that were refractory to conventional therapy. Peripheral blood samples were obtained at days 0, 15, and 180 of Rituximab therapy, and the number and function of regulatory T lymphocytes, as well as the presence of apoptotic cells were analyzed. Five out of seven patients showed significant clinical improvement upon Rituximab therapy (ACR response 50-70), and a significant increase in the number and function of regulatory T cells. In addition, an increased percent of apoptotic cells was detected in the peripheral blood after the onset of Rituximab therapy. These data suggest that Rituximab seems to exert an interesting effect on regulatory T cells in patients with RA; this phenomenon may contribute to the therapeutic effect of this anti-CD20 agent in RA