The effects of rituximab on the lipid profile of patients with active systemic lupus erythematosus: results from a nationwide cohort in Spain (LESIMAB).

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have increased cardiovascular risk related to lipid changes induced by inflammatory activity, proteinuria and treatments. Our objective was to analyse lipid changes in a cohort of patients with SLE resistant to standard treatments who were treated with rituximab. METHODS: The study population comprised a retrospective multicentre, national cohort of patients with SLE resistant to standard treatments who were treated with rituximab. The basic lipid profile, concomitant treatment and disease activity were analysed at the start of the treatment, 24 weeks later, and at the end of the follow-up period. The effects of the main lupus variables and therapy on the lipid changes were analysed. RESULTS: Seventy-nine patients with active lupus treated with rituximab were assessed during 149.3 patient-years. Prior to the treatment, 69% had dyslipidaemia. The most frequent abnormalities were a low-density lipoprotein (LDL) level of ≥100 mg/dl (34%) and a high-density lipoprotein (HDL) level of <50 mg/dl (27%). Baseline total cholesterol (TC) and LDL levels correlated with the degree of proteinuria, while the concentration of triglycerides (TGs) correlated with the SLE Disease Activity Index (SLEDAI). TGs were reduced at short- and long-term follow-up after rituximab treatment. A multiple linear regression analysis identified that the reduction of the lupus inflammatory activity, particularly changes in proteinuria, was the only independent variable that was positively associated with the reduction in TGs after 24 weeks (p=0.001) and with TC (p=0.005) and TGs (p<0.001) at the end of the follow-up period. CONCLUSION: Our results suggest that rituximab may improve the long-term lipid profile of patients with SLE refractory to standard treatment, mainly by reducing inflammatory activity.

Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study.

OBJECTIVE: This study aimed to investigate the effectiveness and safety of single and repeated courses of rituximab in patients with refractory lupus. METHODS: LESIMAB is a multicenter, retrospective, longitudinal study of lupus patients who have not responded to standard therapy and have been treated with rituximab. Response rates at six months and at follow-up were defined as efficacy outcomes. Complete response was defined as a SELENA-SLEDAI score ≤ two and a SELENA-SLEDAI Flare Index of zero. Partial response was defined as a reduction in the SELENA-SLEDAI score of ≥four points with no new or worsening of symptoms. Adverse events were collected. RESULTS: Seventy-three (62.9%) of 116 patients achieved a response at six months (complete in 22 and partial in 51). Ninety-seven (77.6%) of 128 patients achieved a response after a mean follow-up of 20.0 ± 15.2 months (complete in 50 and partial in 47). High baseline SLEDAI score, previous treatment with ≥100 mg/day prednisone, and no history of severe hematologic flare were associated with response after the first treatment course. The median time to response was 6.5 months (95% CI, 5.0-8.0). Thirty-seven patients (38.1%) relapsed after the first infusion. The flare was severe in seven cases and mild to moderate in 29 cases. Serious infection rate was 12.6/100 patient-years. A schedule of four weekly doses was associated with more serious infections. Six patients died: two of infection and four of lupus complications. CONCLUSION: Rituximab can be an effective treatment option for patients who have refractory lupus with severe or life-threatening disease with an acceptable tolerance profile.

Detección de anticuerpos anti-RNP y anti-Sm mediante immunoblotting y contrainmunoelectroforesis utilizando el mismo extracto de timo de conejo / Detection of anti-RNP and anti-Sm antibodies by immunoblotting and contrainmmunoelectrophoresis using the same rabbit thymus extract

Las técnicas de contrainmunoelectroforesis (CIE) y ELISA son útiles para detectar anticuerpos anti-RNP y anti-Sm,pero no identifican los anticuerpos dirigidos contra los diferentes polipéptidos asociados a RNP/Sm.Estos anticuerpos pueden detectarse mediante immunoblotting (IB) con extractos de células HeLa u otras mantenidad en cultivo.Objetivos:Determinar si el mismo extracto de timo de conejo utilizado en la CIE puede ser una alternativa válida ppara detectar mediante IB los anticuerpos dirigidos contra los diferentes polipépticos asociados a RNP/Sm.Métodos:Hemos estudiado 342 sueros de 250 pacientes con enfermedades inflamatorias del tejido conjuntivo.Los anticuerpos anti-RNP y anti-Sm fueron detectados mediante CIE e IB utilizando como sustrato el mismo extracto comercial de timo de conejo.Resultados: Este IB permitió anticuerpos dirigidos contra los polipéptidos 70kD,A,BB',C y D,aunque el de 70D estaba degradado.Se detectaron anticuerpos anti-RNP y anti-Sm por CIE en el 7,3 por ciento (25 de 342) y de 6,1 (21 de 342) de los sueros , y mediante IB en el 14,9 por ciento (51 de 342) y de 14,3//(49 de 342) de los sueros,respectivamente.En 72 pacientes con lupus eritematoso sistémico la sensibilidad y especificidad de la CIE fueron del 19,1//y del 96,5//para anti-RNP,y del 11,1 del del 100//para anti-Sm.La sensibilidad y especificidad del IB fueron del 22,2 y del 96//para anti-RNP 70 kD y del 19,4 y del 100//para anti-SmD. Conclusiones: A pesar de la degradación proteolítica , el IB con un extracto soluble de timo de conejo puede ser una alternativa válida como complemento de la CIE o del ELISA en la detección de anticuerpos anti-RNP y anti-Sm,y está al alcance de cualquier laboratorio clínico.

Detección de anticuerpos anti-RNP y anti-Sm mediante immunoblotting y contrainmunoelectroforesis utilizando el mismo extracto de timo de conejo / Detection of anti-RNP and anti-Sm antibodies by immunoblotting and contrainmmunoelectrophoresis using the same rabbit thymus extract

Las técnicas de contrainmunoelectroforesis (CIE) y ELISA son útiles para detectar anticuerpos anti-RNP y anti-Sm,pero no identifican los anticuerpos dirigidos contra los diferentes polipéptidos asociados a RNP/Sm.Estos anticuerpos pueden detectarse mediante immunoblotting (IB) con extractos de células HeLa u otras mantenidad en cultivo.Objetivos:Determinar si el mismo extracto de timo de conejo utilizado en la CIE puede ser una alternativa válida ppara detectar mediante IB los anticuerpos dirigidos contra los diferentes polipépticos asociados a RNP/Sm.Métodos:Hemos estudiado 342 sueros de 250 pacientes con enfermedades inflamatorias del tejido conjuntivo.Los anticuerpos anti-RNP y anti-Sm fueron detectados mediante CIE e IB utilizando como sustrato el mismo extracto comercial de timo de conejo.Resultados: Este IB permitió anticuerpos dirigidos contra los polipéptidos 70kD,A,BB,C y D,aunque el de 70D estaba degradado.Se detectaron anticuerpos anti-RNP y anti-Sm por CIE en el 7,3 por ciento (25 de 342) y de 6,1 (21 de 342) de los sueros , y mediante IB en el 14,9 por ciento (51 de 342) y de 14,3//(49 de 342) de los sueros,respectivamente.En 72 pacientes con lupus eritematoso sistémico la sensibilidad y especificidad de la CIE fueron del 19,1//y del 96,5//para anti-RNP,y del 11,1 del del 100//para anti-Sm.La sensibilidad y especificidad del IB fueron del 22,2 y del 96//para anti-RNP 70 kD y del 19,4 y del 100//para anti-SmD. Conclusiones: A pesar de la degradación proteolítica , el IB con un extracto soluble de timo de conejo puede ser una alternativa válida como complemento de la CIE o del ELISA en la detección de anticuerpos anti-RNP y anti-Sm,y está al alcance de cualquier laboratorio clínico.

[Clinical and serologic course of patients with mixed connective tissue disease]. / Evolución clínica y serológica en pacientes con enfermedad mixta del tejido conectivo.

The so called mixed connective tissue disease (MCTD), continues to be a controversial entity, while some authors considered it a good characterized disease, others think that is an undifferentiated connective tissue disease. OBJECTIVE. To analyse the clinical and serological evolution of a group of patients diagnosed of MCTD, with particular consideration to the meaning of anti-nRNP and anti-Sm antibodies. METHOD. We have studied 20 patients diagnosed of MCTD and 112 with systemic lupus erythematosus (SLE). Anti-nRNP and anti-Sm antibodies were detected through counter immunoelectrophoresis, immunoblotting and ELISA. RESULTS. After an average time of evolution of 10 years, 70% (14/20) of the patients diagnosed of MCTD fulfill criteria for SLE (6 cases), scleroderma (6 cases) or polymyositis (2 cases). Anti-nRNP response is persistent, directed mainly against the 70 Kd and A-nRNP polypeptides and qualitatively higher in MCTD in SLE (absorbencies 2.64 vs 1.25. The immunoblotting test detected anti-Sm antibodies in 5 patients (25%) and ELISA test in 14 (70%). CONCLUSIONS. Clinical and serological evolution suggest that MCTD is an undifferentiated connective tissue disease. Anti-nRNP antibodies are characteristic, although anti-Sm antibodies can be detected with ELISA regardless whether on not patients fulfill SLE criteria.