ABSTRACT
Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects 0.8 percent of the world population, it affects the synovial membrane of joints and the clinical presentation encompasses a wide spectrum, ranging from a mild to a severe and erosive disease that causes joint and cartilage destruction which finally provokes irreversible structural damage and patient disability. In the last years, there have been important advances in the pathogenesis of this disease, the efforts have been concentrated on pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha). This protein guides numerous events in the synovial and systemic inflammatory process and is encoded in the Major Histocompability Complex (MHC), one of the most polymorphic of the genome. Polymorphisms affecting the TNFalpha gene and its regulatory regions are associated with RA prevalence and course. There is a possible association between these polymorphisms and the clinical response to the use of monoclonal antibodies anti-TNFalpha. The possibility that the determination of genotypes -238 and -308 may have prognostic and therapeutic consequences is debated nowadays (Rev Méd Chile 2005; 133: 1089-95).
Subject(s)
Humans , Antibodies, Monoclonal/therapeutic use , Arthritis, Rheumatoid , Polymorphism, Genetic , Tumor Necrosis Factor-alpha/genetics , Promoter Regions, Genetic , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , GenotypeABSTRACT
The use of biological agents such as etanercept, infliximab, adalimumab and anakinra has been recently approved for the treatment of rheumatoid arthritis. All are effective controlling signs and symptoms and inhibiting disease progression. To overcome the problems generated by their high costs and possible participation in reactivating latent infections, other therapeutic tools are being developed. Gene therapy using expression vectors carrying genes coding for specific proteins, may interfere in key points involved in the pathogenesis of the disease. Intra-articular administration of cDNA coding for soluble TNF receptors, IL-1, or IL-1Ra decreases signs of the disease in animal models. Vectors, expressing inhibitors of signal transduction pathways involving to NF-kB and JAK-STAT-3, are effective in modulating joint inflammation in mice. The use of antigen-pulsed antigen presenting cells or dendritic cells (DC) bound to apoptosis-inducing molecules, specifically eliminates autoreactive T cells. Other novel approach attempts the development of T regulatory-inducing tolerogenic DC-based vaccines that inhibit autoreactive T cells, through the secretion of suppressing cytokines or by other mechanisms to be elucidated. Oral tolerance induction to auto-antigens is also a successful experimental strategy under study. Current research aims to control peripheral tolerance in rheumatoid arthritis patients.
Subject(s)
Animals , Humans , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Immunologic Factors/therapeutic use , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Drug Therapy, Combination , Genetic TherapyABSTRACT
New therapeutic approaches that include depletion of B cells using rituximab, a chimeric monoclonal antibody directed against the B cell specific antigen CD-20 have been developed for the treatment of systemic lupus erythematosus (SLE). We report the case of a 18 years old girl with SLE that did not respond and experienced adverse effects with the use of hydroxycloroquine, methotrexate, mycophenolate mofetil, azathioprine and high-dose steroids. Rituximab was given weekly at 375 mg/m2 for four doses. The drug was well tolerated and the patient had no adverse reactions. She remains asymptomatic three months later.
Subject(s)
Adolescent , Female , Humans , Antibodies, Monoclonal/therapeutic use , Immunologic Factors/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Antibodies, Monoclonal/immunology , Immunologic Factors/immunologyABSTRACT
La artritis Reumatoídea es una enfermedad inflamatoria sistémica, crónica, de curso habitualmente progresivo, en cuya etiología interactúan mecanismos ambientales favorecidos por una predisposición genética. Existe un amplio espectro de citoquinas involucradas en la patogenia. Entre ellas, el Factor de Necrosis Tumoral Alfa (TNFa) juega un rol protagónico. Esto se ha visto confirmado en el último tiempo con las nuevas terapias biológicas que bloquean la acción de esta citoquina, logrando respuestas de gran impacto en la calidad de vida de los pacientes. En el presente artículo se revisan los elementos que ayudan a entender la fisiopatología, mecanismos reguladores y la importancia de determinar el polimorfismo del promotor del gen del TNF a-308, basados en la experiencia de un grupo de investigación nacional.
Subject(s)
Humans , Tumor Necrosis Factor-alpha , Arthritis, Rheumatoid , Chile , Polymorphism, GeneticABSTRACT
The target cellular response to glucocorticoids is proportional to the concentration or affinity of specific receptors to these substances. To look for a correlation between glucocorticoid receptors concentrations in synovial wall cells and the clinical response to steroidal treatment in patients with rheumatoid arthritis. Twenty eight patients with rheumatoid arthritis were studied. Each subject was subjected to a synovial biopsy in which a dry radioautographic technique for diffusable compounds was used. Patients were treated afterwards with 3 500mg iv pulses of methilprednisolone. A mean of 44.8 percent of synovial cells (range 30.1-62.8 percent) had binding sites for 3H dexamethasone. All patients had a significant clinical improvement after methilprednisolone. Multiple regression analysis did not show a correlation between clinical response and glucocorticoid receptor concentration. The lack of association between glucocorticoid receptor concentration and clinical response could be due to the large steroid dose used, that saturated all available receptors
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Arthritis, Rheumatoid/drug therapy , Glucocorticoids/pharmacokinetics , Anti-Inflammatory Agents/pharmacokinetics , Synovial Membrane/drug effects , Synovial Membrane/pathology , Methylprednisolone/pharmacokineticsABSTRACT
The effectiveness, toxicity and prognosis factors influencing responses to cyclophosphamide (CP) iv pulses plus oral glucocorticosteroids (GC) in patients with GC-resistant ocular inflammatory diseases (OID) was evaluated in a cohort of 15 consecutive patients suffering from active, non-infectious OID refractory to oral GC. All patients underwent monthly evaluations with clinical, hematological, hepatic, renal and ophthalmologic tests. These included checking visual acuity and both anterior chamber and posterior segment inflammation. The overall effect evaluated by repeated measurements ANOVA demonstrated that after an average of 5 CP pulses 1-10, the group showed significant improvement regarding of visual aciuty and inflammation (p<0,000001). Amelioration was not sustained over time in patients with granulomatous iveitis. Patients with retinal vasculitis experienced rapid and sustained recovery. By the end of the follow-up period, 53 percent of the patients had improved, 20 percent remained stationary and 26 percent suffered visual acuity deterioration as compared with the baseline. No serious side effects were detected during treatment and follow-up. Conclusions: a combination of oral GC and iv CP pulses appears to be an effective way to treat patients suffering from noninfectious, non-granulomatous, GC-resistant OID
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Uveitis/drug therapy , Prednisone/administration & dosage , Cyclophosphamide/administration & dosage , Uveitis/complications , Clinical ProtocolsABSTRACT
We report a 50 years old male that evolved with alternating episodes of osteoporosis with pain, edema and erythema of both feet. The patient presented clinical and radiological evidences of both transient regional osteoporosis and reflex sympathetic dystrophy. The clinical evolution was documented with magnetic resonance imaging. The hypothesis that bothe entities could be different expressions of a same syndrome is discussed
Subject(s)
Humans , Male , Middle Aged , Osteoporosis/diagnosis , Reflex Sympathetic Dystrophy/diagnosis , Osteoporosis/therapy , Calcitonin/administration & dosage , Prednisone/administration & dosage , Guanethidine/administration & dosage , Hyperaldosteronism/complications , Diagnosis, Differential , Reflex Sympathetic Dystrophy/therapy , Magnetic Resonance SpectroscopyABSTRACT
We analyzed the reuslts of bronchoalveolar lavage (BAL) in 14 patients with Rheumatoid Arthritis. Teh patients had total cell counts above 10 x 10***6/100 ml and or more than 10½ lymphocytes in differential counts. 40% of patients with normal clincial findings on pulmonary examination and normal A-a 02 gradients had abnormal BAL findings. These findings support the theory that pulmonary fibrosis in patients with RA may start with alveolitis, probably a lymphocytic in 60% of cases. BAL may help early diagnosis and treatment monitoring