RESUMEN
OBJECTIVES: Although T cells are thought to be involved in the pathogenesis of PMR, whether innate-like T cells are involved in the process remains unknown. METHODS: The serum levels of 27 cytokines/chemokines in patients with PMR were measured by a multiplex immunoassay (Bio-Plex Assay). The cytokine-producing capacity of T and innate-like T cells was assessed by intracellular cytokine staining and flow cytometry. The frequency and activated status of T and innate-like T cells were investigated by flow cytometry and their associations with clinical parameters were assessed. RESULTS: The levels of inflammatory cytokines were associated with disease activity in PMR. The cytokine-producing capacity by CD8+ T and innate-like T cells was associated with disease activity. The frequency of HLA-DR+ CD38+ cells among CD8+ T cells was increased in patients with active disease. The frequencies of HLA-DR+ CD38+ cells among CD4+ T, mucosal-associated invariant T (MAIT) and γδ T cells were higher in patients with inactive disease. The frequency of HLA-DR+ CD38+ MAIT cells was associated with the PMR activity score and CRP levels in patients in remission. CONCLUSION: The inflammatory cytokine-producing capacity and expression of activation markers of CD8+ T and innate-like T cells were associated with the disease activity of PMR. MAIT cell activation in patients in remission may contribute to the subclinical activity of the disease.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Citocinas/sangre , Células T Invariantes Asociadas a Mucosa/inmunología , Polimialgia Reumática/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Quimiocinas/sangre , Femenino , Citometría de Flujo , Humanos , Inmunidad Celular , Activación de Linfocitos , Masculino , Polimialgia Reumática/sangre , Polimialgia Reumática/patologíaRESUMEN
Objective The objective of this study was to confirm the efficacy of low-dose mizoribine (MZR), an inhibitor of inosine monophosphate dehydrogenase, as part of synchronized methotrexate (MTX) therapy for rheumatoid arthritis (RA) patients with an inadequate response to various combination therapies of MTX, other synthetic disease-modifying anti-rheumatic drugs (DMARDs) and biological DMARDs. Methods Low-dose MZR was administered to 56 uncontrolled RA patients being treated with MTX and various biological DMARDs. The observation period was 12 months, and the disease activity was evaluated based on the Disease Activity Score in 28 joints (DAS28)-ESR, Simplified Disease Activity Index (SDAI) and serum MMP-3 level. Results All of the disease activity indices were significantly improved within three months, and the serum MMP-3 levels were also significantly decreased around four months after starting low-dose MZR therapy. No patients experienced any adverse effects. Conclusion The present preliminary findings suggest that low-dose MZR therapy with MTX should be considered for the treatment of RA patients with an inadequate response to various combination therapies including MTX, other synthetic DMARDs and biological DMARDs or in whom increasing the dose of MTX is difficult for reasons such as adverse effects and complications.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Metotrexato/uso terapéutico , Ribonucleósidos/uso terapéutico , Anciano , Antirreumáticos/administración & dosificación , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Humanos , Masculino , Metaloproteinasa 3 de la Matriz/metabolismo , Metotrexato/administración & dosificación , Persona de Mediana Edad , Proyectos Piloto , Ribonucleósidos/administración & dosificación , Resultado del TratamientoRESUMEN
A 31-year-old woman with systemic lupus erythematosus and lupus nephritis was treated with prednisone and immunosuppressants. After her lupus nephritis symptoms worsened, both high-dose steroid and cyclophosphamide pulse therapy were administered. The patient developed an intestinal perforation, and laparoscopic Hartmann's surgery was performed on the sigmoid colon. Serum Cytomegalovirus (CMV) antigen C7HRP was detected, and the patient was diagnosed with CMV colitis and underwent a colon resection. Severe hematochezia continued despite ganciclovir administration, and the patient underwent laparoscopic total colectomy and partial ileostomy. CMV enteritis should be considered in patients treated with prednisone and immunosuppressants and those who have abdominal pain and hematochezia. Immunocompromised patients with intestinal perforation due to CMV enteritis have a poor prognosis. We report a case with along with the results of a literature review.
Asunto(s)
Colitis/complicaciones , Infecciones por Citomegalovirus/complicaciones , Enteritis/complicaciones , Huésped Inmunocomprometido , Perforación Intestinal/etiología , Nefritis Lúpica/complicaciones , Adulto , Antivirales/uso terapéutico , Betametasona/administración & dosificación , Betametasona/efectos adversos , Colon Sigmoide/cirugía , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/tratamiento farmacológico , Enteritis/virología , Femenino , Ganciclovir/uso terapéutico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Perforación Intestinal/cirugía , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/inmunología , Prednisolona/administración & dosificación , Prednisolona/efectos adversos , Tacrolimus/administración & dosificación , Tacrolimus/efectos adversosRESUMEN
A patient with severe lupus nephritis developed thrombocytopenia during treatment with high-dose steroids. In addition to viral- or disease-induced cytopenia, the pathology was believed to arise from diverse contributing factors, such as thrombotic microangiopathy and heparin-related thrombocytopenia (HIT). By combining plasma exchange therapy and intravenous cyclophosphamide, we successfully controlled the SLE activity and improved the thrombocytopenia. An antecedent bacterial infection or SLE activity is believed to have contributed to the concurrent HIT.
RESUMEN
OBJECTIVE: Ankylosing spondylitis (AS) is characterized by chronic inflammation of the axial and peripheral joints and ligamentous attachments. Gut immunity is thought to be involved in AS, because a prominent coexistence of gut and joint inflammation has been observed in patients with AS. Mucosal-associated invariant T (MAIT) cells are preferentially located in the gut lamina propria and produce inflammatory cytokines such as interleukin 17 (IL-17) and tumor necrosis factor-α (TNF-α), which are therapeutic targets for AS. This study aimed to investigate the involvement of MAIT cells in AS. METHODS: The frequency of MAIT cells and their cytokine production were determined in patients with AS and healthy controls (HC). The expression of a MAIT cell activation marker (CD69) was analyzed in patients with AS by using flow cytometry. RESULTS: The frequency of MAIT cells in the peripheral blood was lower in patients with AS compared with HC. The levels of IL-17 produced by MAIT cells after activation were higher in patients with AS than in the HC. CD69 expression on MAIT cells correlated with the Ankylosing Spondylitis Disease Activity Score in patients with AS. CONCLUSION: These results suggest the involvement of MAIT cells in the pathogenesis of AS.
Asunto(s)
Citocinas/metabolismo , Activación de Linfocitos/inmunología , Células T Invariantes Asociadas a Mucosa/inmunología , Espondilitis Anquilosante/inmunología , Adulto , Femenino , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Células T Invariantes Asociadas a Mucosa/metabolismo , Espondilitis Anquilosante/metabolismoRESUMEN
That boronic acid is a reactive species toward a diol moiety even in an alkaline solution and that the boronate ion is not very reactive were demonstrated by the estimated upper limit of the rate constants for the reactions of some boronic acids with 2,2'-biphenol and 2,3-dihydroxynaphthalene in a neutral-alkaline solution, which will correct a common misunderstanding in boron chemistry and would renew the idea of effective boronic acid sensor design for carbohydrates.