RESUMEN
OBJECTIVES: Systemic sclerosis (SSc) is a multiorgan disease with a 10-year mortality rate of up to 50 %. B cell-depleting therapy with rituximab (RTX) appears effective in SSc treatment, but data from randomized controlled trials (RCTs) are lacking, and the frequency and dosage of RTX in SSc have no consensus. We aimed to evaluate the long-term efficacy and safety of quarterly RTX administration in SSc. METHODS: This study retrospectively analyzed 40 patients with SSC treated with RTX twice within 14 days every 3 months from 2010 to 2020. The patients fulfilled the LeRoy and the American College of Rheumatology/European League Against Rheumatism Criteria for SSc. Modified Rodnan skin score (mRSS), lung function test results, and serum immunoglobulin (IgG, IgA, and IgM) concentrations were analyzed. RESULTS: A total of 40 patients with SSc received RTX over a median time of 3.9 years (range: 1-10 years). The median mRSS (baseline: 19, 24 months: 16, p < 0.001) demonstrated a significant improvement, and the predicted forced vital capacity was stable. No new or unexpected safety signals, especially regarding treatment-related infectious adverse events, were observed. Immunoglobulin concentrations were within normal range, and specific antibodies to pneumococcal polysaccharides were preserved despite long-term B cell-depleting therapy. None of the patients died during the observation period of up to 10 years. CONCLUSION: SSc was effectively and safely treated with low-dose RTX quarterly. RCTs are warranted to validate the advantage of continuous B cell depletion by quarterly low-dose RTX administration compared to other treatment intervals.
Asunto(s)
Linfocitos B , Depleción Linfocítica , Rituximab , Esclerodermia Sistémica , Humanos , Esclerodermia Sistémica/mortalidad , Esclerodermia Sistémica/inmunología , Esclerodermia Sistémica/terapia , Esclerodermia Sistémica/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Linfocitos B/inmunología , Rituximab/uso terapéutico , Estudios Retrospectivos , Adulto , Resultado del Tratamiento , AncianoAsunto(s)
Antirreumáticos/uso terapéutico , Autoanticuerpos/sangre , Rituximab/uso terapéutico , Esclerodermia Difusa/tratamiento farmacológico , Esclerodermia Difusa/inmunología , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Autoanticuerpos/inmunología , Biomarcadores/sangre , ADN-Topoisomerasas de Tipo I/sangre , ADN-Topoisomerasas de Tipo I/inmunología , Relación Dosis-Respuesta a Droga , Humanos , Vigilancia Inmunológica , Esclerodermia Difusa/sangre , Sensibilidad y Especificidad , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Cartílago Articular/metabolismo , Regulación de la Expresión Génica/fisiología , Laminina/fisiología , Metaloproteinasa 3 de la Matriz/genética , Osteoartritis/metabolismo , Cartilla de ADN/química , Humanos , Inmunohistoquímica , Metaloproteinasa 3 de la Matriz/metabolismo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVE: Sphingosine-1-phosphate (S1P) is a messenger molecule, with important functions in inflammation and wound healing. The present study was performed to elucidate a possible role of S1P signaling in articular chondrocytes. METHODS: Human and bovine primary chondrocytes were cultured in monolayer. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect S1P receptor mRNA. Proliferation of S1P stimulated chondrocytes was measured by 3H-thymidine uptake. Supernatants of cultured bovine chondrocytes stimulated with S1P alone or in combination with interleukin-1beta (IL-1beta) were tested for nitric oxide (NO) formation and expression of inducible nitric oxide synthase (iNOS). Matrixmetalloprotease-13 (MMP-13) and aggrecanase-1 (ADAMTS-4) were evaluated using real-time PCR. Glycosaminoglycan (GAG) loss from bovine cartilage explants was evaluated using the dimethylene blue method. RESULTS: S1P1, S1P2 and S1P3 but not S1P4 and S1P5 receptor mRNA were detected in human and bovine chondrocytes. S1P dose dependently induced proliferation in bovine and human chondrocytes. S1P significantly reduced NO formation and iNOS mRNA and protein expression, both in un-stimulated and IL-1beta stimulated bovine chondrocytes. Furthermore, S1P dose dependently inhibited IL-1beta induced expression of ADAMTS-4 and MMP-13 and diminished IL-1beta mediated GAG depletion from cartilage explants. CONCLUSION: These results suggest that S1P provides an anti-catabolic signal in articular chondrocytes.