Rheumatic Aschoff nodules revisited. II: Cytokine expression corroborates recently proposed sequential stages

Fraser, W.J.; Haffejee, Z.; Jankelow, David; Wadee, Ahmed A.; Cooper, Kumarasen

doi:10.1046/j.1365-2559.1997.2990883.x

Cited by 44 publications

(20 citation statements)

References 8 publications

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“…In RF and RHD, increased plasma levels of TNF-a have been demonstrated [23][24][25]. TNF-a (also IL-1 and IL-2) production in the valvular lesions of RF patients was correlated with Aschoff nodule progression [26]. It is possible that TNF-a gene polymorphism interferes with inflammatory response by influencing the levels of the cytokine, but linkage disequilibrium with MHC class II (both located on chromosome 6) is an alternative.…”

Section: Genetic Contribution To Susceptibilitymentioning

confidence: 99%

Understanding rheumatic fever

2011

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Through a comprehensive review of the recent findings on rheumatic fever, we intend to propose a new physiopathologic model for this disease. A Medline search was performed for all articles containing the terms rheumatic fever or rheumatic heart disease in title or abstract from 1970 to 2011. Best evidence qualitative technique was used to select the most relevant. The scientific interest on rheumatic fever has notably diminished throughout the twentieth century as evidenced by the comparison of the proportion of articles in which RF was a subject in 1950 (0.26%) and today (0.03%) [Pubmed]. However, RF remains a major medical and social problem in the developing world and in the so-called hotspots, where it still causes around 500.000 deaths each year, not too different from the pre-antibiotic era. The role of genetic factors in RF susceptibility is discussed. Familiar aggregation, similarity of disease patterns between siblings, identical twin, and HLA correlation studies are evidence for a genetic influence on RF susceptibility. The suspect-involved genes fall mainly into those capable of immunologic mediation. Molecular mimicry explains the triggering of RF, but an intense and sustained inflammation is needed to cause sequels. Also, RF patients vary greatly in terms of symptoms. It is likely that a genetic background directing immune response towards a predominantly Th1 or Th2 pattern contributes to these features. The recent findings on rheumatic fever provide important insight on its physiopathology that helps understanding this prototype post-infectious autoimmune disease giving insights on other autoimmune conditions.

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Section: Genetic Contribution To Susceptibilitymentioning

confidence: 99%

Understanding rheumatic fever

2011

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“…In rheumatic Aschoff nodules, a central necrotic focus is surrounded by immune giant cells and lymphocytes, and these cells have been shown to participate in the resorption of necrotic and fibrous tissue of rheumatoid nodules [152] . Fraser et al [153] proposed that these lesions exhibit progressive phases, with the early phases characterized by macrophage influx and production of IL-1 and TNF-␣ , followed by later stages of T and B cell recruitment and activation, as well as IL-2 production. The recruitment and activation of macrophages, as well as the formation of multinucleated giant cells, suggests that NADPH oxidase assembly and ROS production would be a prominent feature of this lesion that could participate in tissue resorption and repair; however, the actual role of ROS in this pathologic process has not been evaluated.…”

Section: Rheumatoid Diseasesmentioning

confidence: 99%

Role of NADPH Oxidase in Formation and Function of Multinucleated Giant Cells

Quinn

Schepetkin²

2009

J Innate Immun

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Macrophages play essential roles in a wide variety of physiological and pathological processes. One of the unique features of these phagocytic leukocytes is their ability to fuse, forming multinucleated giant cells. Multinucleated giant cells are important mediators of tissue remodeling and repair and are also responsible for removal or sequestration of foreign material, intracellular bacteria and non-phagocytosable pathogens, such as parasites and fungi. Depending on the tissue where fusion occurs and the inflammatory insult, multinucleated giant cells assume distinctly different phenotypes. Nevertheless, the ultimate outcome is the formation of large cells that can resorb bone tissue (osteoclasts) or foreign material and pathogens (giant cells) extracellularly. While progress has been made in recent years, the mechanisms and factors involved in macrophage fusion are still not fully understood. In addition to cytokines and a number of adhesion proteins and receptors, it is becoming increasingly clear that NADPH oxidase-generated reactive oxygen species (ROS) also play an important role in macrophage fusion. In this review, we provide an overview of macrophage multinucleation, with a specific focus on the role of NADPH oxidases and ROS in macrophage fusion and in the function of multinucleated giant cells. In addition, we provide an updated overview of the role of these cells in inflammation and various autoimmune diseases.

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“…In heart lesions during the acute phase of RHD, the production of IL-1, TNFα and IL-2 was correlated with progression of the Aschoff nodule [55]localized mainly in the endocardium, subendocardium or perivascular regions of the myocardial interstitium.…”

Section: Cytokinesmentioning

confidence: 99%

Rheumatic Fever: From Sore Throat to Autoimmune Heart Lesions

Guilherme

Kalil

2004

Int Arch Allergy Immunol

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Molecular mimicry between streptococci and heart components has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). In this review, we present data from cellular autoimmune responses, focusing on the interactions between HLA class II molecules, streptococcal peptides and heart tissue proteins and T-cell receptor (TCR) usage. HLA-DR7DR53 associated with DQ molecules seem to be related with the development of valvular lesions in severe RHD patients. DR7DR53 molecules were also involved in the recognition of an immunodominant M5 peptide in these patients. T cells infiltrating RHD hearts displayed several oligoclonal expansions. Intralesional T-cell clones presenting identical TCR-BVBJ AVAJ and -CDR3 sequences were able to recognize several antigens with little or low homology, showing an intramolecular degenerate pattern of antigen recognition. Peripheral blood mononuclear cells of rheumatic fever (RF) patients produced proinflammatory cytokines, and intralesional mononuclear cells from severe RHD patients produced predominantly Th1-type cytokines. These results illustrate the complex mechanisms leading to heart tissue damage in RF/RHD patients.

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Rheumatic Aschoff nodules revisited. II: Cytokine expression corroborates recently proposed sequential stages

Cited by 44 publications

References 8 publications

Understanding rheumatic fever

Understanding rheumatic fever

Role of NADPH Oxidase in Formation and Function of Multinucleated Giant Cells

Rheumatic Fever: From Sore Throat to Autoimmune Heart Lesions

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