Podocyte research in rheumatic diseases

Podocytes are glomerular visceral epithelial cells, which function as molecular sieve with foot process (FT) and slit diaphragm (SD) spanning FT, not to allow high molecular weight protein to be filtrated through glomerular capillary loop. Pathological proteinuria is caused by discoordinated tertiary podocyte structure such as disappearance of FT and/or SD, and irreversible glomeular sclerosis is caused by podocyte loss due to cell death and/or detachment from capillary wall. With recent advance of nephrological research technology such as podocyte cell culture system, genetically engineered transgenic mice with podocyte-specific regulation of gene expression, podocyte-associated biomarkers, the new isolation method of glomeruli, laser capture microdissection, multiphoton imaging and extracellular flux analyzer, new findings of pathogenesis of glomerular lesions will be expected, not only in primary glomerulonephritis, but also in secondary glomerulonephritis or glomerulopathy due to rheumatic diseases.     

Vaccination and autoimmune rheumatic diseases

Patients with autoimmune rheumatic diseases are at increased risk of developing infections. However, concerns about the safety and the immunogenicity of vaccines in these patients limited their use. Most of the data against the use of vaccines come from the reported cases of previously healthy individuals who presented the onset of rheumatic diseases after immunization, nevertheless a causal relationship has not been established. During the past few decades influenza and pneumococcal vaccines, administered to patients with systemic lupus erythematosus, were found to be safe and, generally, serologically effective, even though there is the possibility of inadequate response, especially in patients receiving immunosuppressive agents. In patients with rheumatoid arthritis influenza and pneumococcal vaccines can be considered safe and immunogenic in most cases. Treatment with TNFalpha blocking agents did not appear to impair the immune response.     

Glucocorticoid-induced osteoporosis in rheumatic diseases

The aim of this article is to review rheumatological diseases that are associated with glucocorticoid-induced osteoporosis or fractures and to perform a critical analysis of the current guidelines and treatment regimens. The electronic database MEDLINE was searched using the date range of July 1986 to June 2009 and the following search terms: osteoporosis, bone mineral density, fractures, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, vasculitis, juvenile rheumatoid arthritis, juvenile idiopathic arthritis and juvenile dermatomyositis. Osteopenia and osteoporosis respectively account for 1.4 to 68.7% and 5.0 to 61.9% of adult rheumatological diseases. Among juvenile rheumatological disorders, the frequency of low bone mass ranges from 38.7 to 70%. In general, fracture rates vary from 0 to 25%. Although glucocorticoid-induced osteoporosis has a high rate of prevalence among rheumatic diseases, a relatively low number of patients on continuous glucocorticoid treatment receive adequate diagnostic evaluation or preventive therapy. This deficit in patient care may result from a lack of clear understanding of the attributed risks by the patients and physicians, the high complexity of the treatment guidelines and poor patient compliance.     

食物不耐受与慢性肾脏疾病及风湿性疾病的关系

食物不耐受是国内外研究的热点,其发生率在逐年上升,但目前在许多方面尚存在争议.研究食物不耐受的概念界定、发病机制、诊断、治疗及与肾病综合征、IgA肾病、类风湿性关节炎等常见肾脏疾病及风湿性疾病相关性具有重要意义.     

Pulmonary hypertension in autoimmune rheumatic diseases

Arterial pulmonary hypertension (PH) might be a complication of some autoimmune rheumatic diseases, specially systemic sclerosis. This form of arterial PH is indistinguishable from primary PH, characterised by the presence of plexiform lesions. Although for many years plexiform lesions have been considered end-stage scarring lesions, they are composed by actively proliferating endothelial cells that share many features with cancer cells. Endothelial cells within plexiform lesions in all forms of arterial PH show a decrease in the expression of vasodilator and anti-proliferative factors, and an increase in the expression of vasoconstrictor and angiogenic and mitogenic factors. These cells also show important alterations in growth and apoptosis key regulatory genes. Plexiform lesions are surrounded by inflammatory cell infiltrates, probably providing cytokines that may contribute to the endothelial cell proliferative process. All these data suggest that arterial PH might be seen as a proliferative endothelial cell process, which would open new therapeutic approaches for this devastating disease.     

Microbiota and metabolites in rheumatic diseases

As a gigantic community in the human body, the microbiota exerts pleiotropic roles in human health and disease ranging from digestion and absorption of nutrients from food, defense against infection of pathogens, to regulation of immune system development and immune homeostasis. Recent advances in “omics” studies and bioinformatics analyses have broadened our insights of the microbiota composition of the inner and other surfaces of the body and their interactions with the host. Apart from the direct contact of microbes at the mucosal barrier, metabolites produced or metabolized by the gut microbes can serve as important immune regulators or initiators in a wide variety of diseases, including gastrointestinal diseases, metabolic disorders and systemic rheumatic diseases. This review focuses on the most recent understanding of how the microbiota and metabolites shape rheumatic diseases. Studies that explore the mechanistic interplay between microbes, metabolites and the host could thereby provide clues for novel methods in the diagnosis, therapy, and prevention of rheumatic diseases.     

Cardiovascular disease in autoimmune rheumatic diseases

Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis.     

Accelerated atherogenesis in autoimmune rheumatic diseases

The observation that systemic inflammatory rheumatic diseases such as rheumatoid arthritis (RA) are associated with a significantly increased rate of cardiovascular disease, which often occurs at a younger age than in the normal population, is particularly important given the increasing interest in the role of inflammation in atherogenesis in the general population. This review examines the accumulating evidence for accelerated atherogenesis of RA and updates the hypothesis that vasculitis plays a major role in this. Endothelial dysfunction (ECD), widely regarded as initial lesion in atherogenesis, has been shown to occur commonly in primary vasculitis. This ECD is a diffuse event, demonstrable in more than one vascular bed. It is not simply due to scarring in the vessel wall, related to the focal inflammation of the underlying vasculitis, since it may be reversed by suppression of the immune inflammation. However, the mechanisms for this ECD differ from that of the primary vasculitis. Preliminary evidence suggests that inflammatory mediators such as CRP, TNF, or sphingolipids may be involved. The diffuse ECD of vasculitis may have important consequences for both the progression of the primary disease and for cardiovascular events. A model for the role of vasculitis-induced ECD in the accelerated atherogenesis of rheumatic diseases is presented. These concepts are discussed together with the messages they suggest for 'idiopathic' atherosclerosis in the general population.     

Diagnostic immunopathology of the kidney biopsy in rheumatic diseases

Nephropathies found in systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis, Sj?gren's syndrome, and mixed connective tissue disease are discussed. Pathogenetic insights derived from the study of kidney tissue are highlighted and clinicopathologic correlations indicated. The question of whether to perform kidney biopsy in lupus patients is also addressed.     

Immune complex assays in rheumatic diseases

A wide variety of antigen-nonspecific immune complex assays have been developed in recent years for the detection and quantitation of immune complexes in pathologic fluids. These assays detect complexed antibody regardless of the antigen involved. Almost all of these assays use biologic reagents that may react with substances other than complexed antibody. In addition, the assays do not differentiate nonspecifically aggregated antibody from antigen-complexed antibody. Hence, these assays are not absolute tests for immune complexes. On the basis of studies using these assays, "immune complexes" have been detected in a large number of rheumatic diseases. While these findings have been of considerable investigative interest, thus far they have been of little practical clinical utility. The detection of immune complexes has not been shown to be essential in any clinical conditions but may be helpful in monitoring disease activity in systemic lupus erythematosus (SLE) and may provide useful diagnostic information in two rare syndromes, Lyme arthritis and SLE-related syndrome.     

Laboratory testing for rheumatic diseases]

The diagnosis of rheumatic diseases is primarily based on clinical symptoms and laboratory findings. However, diagnosis of rheumatic disease is often difficult because of the variations even in the same disease. Routine laboratory tests are valuable in detecting renal dysfunctions. In this review, the important auto-antibodies and inflammatory markers associated with rheumatic diseases are described. Further, their utility as diagnostic and prognostic tools, including their specificity, sensitivity and practical applications, is discussed.