RESUMO
BACKGROUND: Namilumab (AMG203) is an immunoglobulin G1 monoclonal antibody that binds with high affinity to the GM-CSF ligand. This was a phase 1b, randomized, double-blind study (PRIORA) to assess namilumab in active, mild-to-moderate rheumatoid arthritis (RA). The primary outcome was the safety and tolerability of repeated subcutaneous injections of namilumab in patients with mild-to-moderate RA. METHODS: Adults with mild-to-moderate RA on stable methotrexate doses for ≥12 weeks were eligible. Patients received three subcutaneous injections of namilumab 150 or 300 mg, or placebo on days 1, 15, and 29, with 12 weeks' follow-up. Primary objective was safety/tolerability. RESULTS: Patients in cohort 1 were randomized to namilumab 150 mg (n = 8) or placebo (n = 5). In cohort 2, patients were randomized to namilumab 300 mg (n = 7) or placebo (n = 4). Incidence of treatment-emergent adverse events (TEAEs) was similar across the three groups (namilumab 150 mg: 63%; namilumab 300 mg: 57%; placebo: 56%). TEAEs in ≥10% of patients were nasopharyngitis (17%) and exacerbation/worsening of RA (13%). No anti-namilumab antibodies were detected. The pharmacokinetics of namilumab were linear and typical of a monoclonal antibody with subcutaneous administration. In a post hoc efficacy, per protocol analysis (n = 21), patients randomized to namilumab showed greater improvement in Disease Activity Score 28 (erythrocyte sedimentation rate and C-reactive protein [CRP]), swelling joint counts and tender joint counts compared with placebo. Difference in mean DAS28-CRP changes from baseline between namilumab and placebo favored namilumab at both doses and at all time points. In addition area under the curve for DAS28-CRP was analyzed as time-adjusted mean change from baseline. A significant improvement in DAS28-CRP was shown with namilumab (150 and 300 mg groups combined) compared with placebo at day 43 (p = 0.0117) and also 8 weeks after last dosing at day 99 (p = 0.0154). CONCLUSIONS: Subcutaneous namilumab was generally well tolerated. Although namilumab demonstrated preliminary evidence of efficacy, patient numbers were small; phase 2 studies are ongoing. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01317797 . Registered 18 February 2011.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antirreumáticos/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The insulin-like growth factor (IGF) system plays a prominent role in the regulation of immunity and inflammation. Inappropriate balance of IGF-1 signaling has been reported in autoimmune disorders. This study was designed to compare +3179G/A IGF-1R genotype distribution in 148 systemic lupus erythematosus (SLE) patients with a group of 240 healthy donors. We also investigated serum IGF-1 levels in SLE patients and healthy controls in an association to genotype. IGF-1 serum levels were measured by enzyme-linked immunosorbent assay and genotyping for the +3179G/A polymorphism was performed by restriction fragment length polymorphisms (RFLP)-polymerase chain reaction (PCR) assay. The higher frequency of homozygous genotype AA (22% vs. 17% with OR 1.319, 95% CI 0.71--2.44) and lower frequency of heterozygous genotype AG (42% vs. 46% with OR 0.698, 95% CI 0.38-1.27) were seen in cases versus controls. Serum IGF-1 levels were comparable between SLE patients and age- and sex-matched healthy donors, even when the groups was stratified according to +3179G/A IGF-1R genotypes. However, when patients were sub grouped according to the disease activity index (SLEDAI score), serum IGF-1 levels were increased in patients with severe disease activity. These results indicated that systemic lupus erythematosus activity is affected by a modulation of the insulin-like growth factor-1 signal pathway and +3179G/A IGF-1R polymorphism.
Assuntos
Fator de Crescimento Insulin-Like I/análise , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Receptor IGF Tipo 1/genética , Adulto , Biomarcadores/sangue , Bulgária , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Connective-tissue disorders, also referred to as collagen-vascular disorders, are characterized by autoantibody-mediated connective-tissue abnormalities. These are also called immune-complex diseases because many involve deposition of immune complexes in specific organ or tissue sites. Some of these disorders are characterized by sterile inflammation, especially of the skin, joints, blood vessels, and kidneys, and are referred to as rheumatic diseases. For inexplicable reasons, many rheumatic diseases primarily affect women. Another major category of connective-tissue diseases includes inherited disorders of bone, skin, cartilage, blood vessels. Examples include Marfan syndrome, osteogenesis imperfecta, and Ehlers-Danlos syndrome. Lupus erythematosus (LE) is the main and most important disease in the group of systemic connective tissue diseases. It is heterogeneous, multiple organs autoimmune inflammatory disease with complex pathogenesis, which is the result of interaction between the susceptible genes and environmental factors that lead to abnormal immune response. In this review will consider: its incidence, pathogenesis, clinical forms and clinical features and diagnosis set based on generally accepted clinical criteria developed by the American College of Rheumatology (ACR), the course of pregnancy in patients suffering from LE, the most common complications of LE during pregnancy and antiphospholipid syndrome as part of LE.
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Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/patologia , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/patologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/patologia , Feminino , Humanos , Fenômenos do Sistema Imunitário , Incidência , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Gravidez , Complicações na Gravidez/imunologiaRESUMO
Diagnosis of Yersinia infections accompanied by reactive arthritis could be complicated by cross-reaction with other arthritogenic bacteria. The possible cross-reaction between Yersinia antigens and anti-Borrelia antibodies in blood sera of patients with Lyme disease was studied. The occurrence of specific IgA, IgG and IgM antibodies was analyzed in serum samples from 30 patients with Yersinia-triggered reactive arthritis, 30 patients with Lyme disease and five samples from healthy blood donors. For anti-Borrelia IgG antibodies, cross-reaction was detected with YopH, YopB, V-ag, YopD, YopN, YopP and YopE, and for IgA with YopD. For IgM, no cross-reaction was detected. Owing to cross-reactivity with Borrelia, the diagnosis of Yersinia-triggered reactive arthritis should be based on a combination of serological and clinical findings.
Assuntos
Anticorpos Antibacterianos/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Borrelia/imunologia , Doença de Lyme/imunologia , Yersinia/imunologia , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Reações Cruzadas , Humanos , Immunoblotting , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Pessoa de Meia-Idade , Yersiniose/diagnósticoRESUMO
Primary Sjögren's syndrome (PSS) is an autoimmune disease of the exocrine glands that is presented with progressive ocular and oral dryness, parotid enlargement and often with systemic (extraglandular) manifestations. In patients with PSS the risk of development of non-Hodgkin's lymphoma (NHL) is 44-fold compared to healthy population. The risk is associated with certain characteristics of the disease's course: recurrent changes in the parotid glands, lymph node enlargement, skin vasculitis, peripheral neuropathy, anemia and lymphopenia. According to the morphologic and phenotypic characteristics, B-cell low-grade lymphomas prevail. This communication presents a 65-year-old woman with PSS who developed a follicular type B-cell NHL 21 years after the autoimmune disease had been diagnosed. The analysis of our case and the literature review summarize the characteristics of the course of PSS, histologic variants, and evolution and prognosis of NHL in this kind of patients.
RESUMO
AIM: To study concentrations of alpha-2-macroglobulin (A-2-MG) in blood serum and synovial fluid (SF) in patients with rheumatoid arthritis and formulation of basic clinical, laboratory and x-ray criteria of RA activity. MATERIALS AND METHODS: A-2-MG levels were measured in the serum and SF from 151 RA patients and in the serum of 20 patients with osteoarthrosis (OA) and 62 healthy donors. The serum concentration for RA patients was 166 +/- 65.3 mg%, for OA patients--175.26 +/- 36.99 mg% and for healthy donors--177.772 +/- 50 mg%. Mean concentration of SF A-2-MG in RA patients was 98.77 +/- 82.43 mg%. CONCLUSION: Changes in the concentration of A-2-MG are unrelated to inflammation activity in the joints of RA and OA patients. Serum and synovial concentration of this protein corresponds to changes in the concentration of IgM and rheumatoid factors in RA patients.
Assuntos
Artrite Reumatoide/sangue , Osteoartrite/sangue , Líquido Sinovial/metabolismo , alfa-Macroglobulinas/metabolismo , Artrite Reumatoide/metabolismo , Biomarcadores , Humanos , Imunodifusão , Osteoartrite/metabolismo , Índice de Gravidade de DoençaRESUMO
Evolution of polyarthritis was elucidated in 115 patients with Reiter's syndrome. There were 67% of men and 33% of women. The mean age of the patients was 33 years. 57% of the patients were HLA B27 carriers. In 70% of the patients, arthritis ran an acute course, in 12%, a subacute course, and 18% developed chronic arthritis. The axial skeleton was involved in 1/3 of the test subjects, enteropathies of different localization were detected in 58% of the cases. The author failed to establish criteria for predicting arthritis chronicity.
Assuntos
Artrite Infecciosa/diagnóstico , Artrite Reativa/diagnóstico , Adulto , Artrite Infecciosa/epidemiologia , Artrite Reativa/epidemiologia , Doença Crônica , Feminino , Antígeno HLA-B27/sangue , Humanos , Masculino , PrognósticoRESUMO
108 patients, 75 men and 33 women, mean age 35 years, with reactive arthritis were studied by microbiological and serological methods for identification of a probable triggering infection. In 32 of the patients a Chlamydia infection, in 30 patients--Yersinia infection, in 7 patients--Staphylococcus infection and in 4 patients--Shigella infection were found. In 27 patients no infectious agent was found but in 4 of them a positive CBR for chlamydia in the sex partner was found. The course of the arthritis is acute or subacute, oligo- or polyarthritis, involving mainly the large joints of the legs. The clinical picture of the arthritis is similar for all etiological forms. This implies a systematic microbiological and serological examination of the patients in order to find out the triggering infection and its appropriate treatment with antibiotics.