菌群变化对类风湿关节炎的影响

目前,对于类风湿关节炎(rheumatoid arthritis,RA)发病机制的研究虽然并不完全清晰,但过去20多年的研究已经使我们对RA的了解增加了很多。遗传因素对RA有很大的影响,但不足以完全解释RA的发生。随着对菌群与RA关系的了解增多,使我们认识到可以利用调节人体菌群的方法,来改善宿主黏膜及更远处的免疫环境以改善RA。目前研究已表明,RA与多个部位的菌群都有一定的关系。本研究将以RA的发病机制与影响因素为基础,对人体口腔、肺部和肠道的菌群变化对类风湿关节炎的影响以及益生菌的治疗作用进行综述。     

Effect of blood transfusion on erythropoiesis of homozygotic beta-thalassemia patients

The influence of blood transfusion on erythropoiesis (bone marrow erythroblasts, peripheral blood erythroblasts and reticulocytes) has been studied in 20 non splenectomized homozygous beta thalassaemia patients aged 3 to 16 years and in 10 splenectomized patients aged 8 to 24 years affected with the same disease. The number of reticulocytes was the same in the two groups but the number of erythroblasts in the splenectomized group was higher than in the other group. There was no correlation between the erythroblasts and the reticulocytes of the peripheral blood on one hand and the haemoglobin level proceeding from the same sample on the other hand. In the non splenectomized group of patients, an inverse relationship was found between the percentage of bone marrow erythroblasts and the mean annual haemoglobin level (r = -0.71; p less than 0.01). These results demonstrate the effect of blood transfusion on the erythroid cell line in homozygous beta thalassaemia and the delay between the transfusions and the medullary erythroblastic response.     

Effect of adalimumab on neutrophil function in patients with rheumatoid arthritis

Neutrophils are known to be targets for the biological activity of tumour necrosis factor (TNF)-α in the pathogenensis of rheumatoid arthritis (RA). Therefore, these cells may be among the targets of anti-TNF-α therapy. In this study we evaluated the effect of therapy with adalimumab (a fully human anti-TNF-α mAb; dosage: 40 mg subcutaneously every other week) on certain phenotypic and functional aspects of neutrophils obtained from 10 selected patients with RA and 20 healthy control individuals. Peripheral blood neutrophils were obtained at baseline and during anti-TNF-α therapy (2, 6 and 12 weeks after the first administration of adalimumab). All patients had been receiving a stable regimen of hydroxychloroquine, methotrexate and prednisone for at least 3 months before and during the study. Baseline neutrophil chemotaxis was significantly decreased in RA patients when compared with control individuals (P < 0.001). Two weeks after the first administration of adalimumab, chemotactic activity was completely restored, with no differences noted between patients and control individuals; these normal values were confirmed 6 and 12 weeks after the start of anti-TNF-α therapy. Phagocytic activity and CD11b membrane expression on neutrophils were similar between RA patients and control individuals; no modifications were observed during TNF-α neutralization. The production of reactive oxygen species, both in resting and PMA (phorbol 12-myristate 13-acetate)-stimulated cells, was significantly higher in RA patients at baseline (P < 0.05) and was unmodified by anti-TNF-α mAb. Finally, we showed that the activation antigen CD69, which was absent on control neutrophils, was significantly expressed on neutrophils from RA patients at baseline (P < 0.001, versus control individuals); however, the molecule was barely detectable on cells obtained from RA patients during adalimumab therapy. Because CD69 potentially plays a role in the pathogenesis of arthritis, our findings suggest that neutrophils are among the targets of anti-TNF-α activity in RA and may provide an insight into a new and interesting mechanism of action of anti-TNF-α mAbs in the control of inflammatory arthritis.     

Identification of blood biomarkers of rheumatoid arthritis by transcript profiling of peripheral blood mononuclear cells from the rat collagen-induced arthritis model

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease that results in joint destruction and subsequent loss of function. To better understand its pathogenesis and to facilitate the search for novel RA therapeutics, we profiled the rat model of collagen-induced arthritis (CIA) to discover and characterize blood biomarkers for RA. Peripheral blood mononuclear cells (PBMCs) were purified using a Ficoll gradient at various time points after type II collagen immunization for RNA preparation. Total RNA was processed for a microarray analysis using Affymetrix GeneChip technology. Statistical comparison analyses identified differentially expressed genes that distinguished CIA from control rats. Clustering analyses indicated that gene expression patterns correlated with laboratory indices of disease progression. A set of 28 probe sets showed significant differences in expression between blood from arthritic rats and that from controls at the earliest time after induction, and the difference persisted for the entire time course. Gene Ontology comparison of the present study with previous published murine microarray studies showed conserved Biological Processes during disease induction between the local joint and PBMC responses. Genes known to be involved in autoimmune response and arthritis, such as those encoding Galectin-3, Versican, and Socs3, were identified and validated by quantitative TaqMan RT-PCR analysis using independent blood samples. Finally, immunoblot analysis confirmed that Galectin-3 was secreted over time in plasma as well as in supernatant of cultured tissue synoviocytes of the arthritic rats, which is consistent with disease progression. Our data indicate that gene expression in PBMCs from the CIA model can be utilized to identify candidate blood biomarkers for RA.     

Identification of blood biomarkers of rheumatoid arthritis by transcript profiling of peripheral blood mononuclear cells from the rat collagen-induced arthritis model

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease that results in joint destruction and subsequent loss of function. To better understand its pathogenesis and to facilitate the search for novel RA therapeutics, we profiled the rat model of collagen-induced arthritis (CIA) to discover and characterize blood biomarkers for RA. Peripheral blood mononuclear cells (PBMCs) were purified using a Ficoll gradient at various time points after type II collagen immunization for RNA preparation. Total RNA was processed for a microarray analysis using Affymetrix GeneChip technology. Statistical comparison analyses identified differentially expressed genes that distinguished CIA from control rats. Clustering analyses indicated that gene expression patterns correlated with laboratory indices of disease progression. A set of 28 probe sets showed significant differences in expression between blood from arthritic rats and that from controls at the earliest time after induction, and the difference persisted for the entire time course. Gene Ontology comparison of the present study with previous published murine microarray studies showed conserved Biological Processes during disease induction between the local joint and PBMC responses. Genes known to be involved in autoimmune response and arthritis, such as those encoding Galectin-3, Versican, and Socs3, were identified and validated by quantitative TaqMan RT-PCR analysis using independent blood samples. Finally, immunoblot analysis confirmed that Galectin-3 was secreted over time in plasma as well as in supernatant of cultured tissue synoviocytes of the arthritic rats, which is consistent with disease progression. Our data indicate that gene expression in PBMCs from the CIA model can be utilized to identify candidate blood biomarkers for RA.     

Effect of gold therapy in rheumatoid arthritis on leukopoiesis and granulocyte phagocytosis]

In 12 patients with rheumatoid arthritis the investigations of leukopoiesis and granulocytic phagocytosis were carried out before and after a gold therapy. A marked reduction of granulocytic phagocytosis could be observed here which decreased after the gold therapy, yet remained below the values of a normal collective. Partly contrary informations are discussed. The disturbance of the phagocytosis capacity of granulocytes may possibly be due to a rheumatic factor.