Leukocyte-endothelial interactions in antineutrophil cytoplasmic antibody-associated systemic vasculitis
ABSTRACT The etiology of ANCA-associated vasculitis is unknown. Currently, it is believed that disease may be triggered by infection with the release of proinflammatory cytokines in genetically susceptible individuals. Priming of PMNs and endothelial cells by these cytokines allows ANCAs to activate PMNs, with damage localized to the endothelium, resulting in early lesions. Damage and activation of endothelial cells produces proinflammatory chemokines and cytokines with influxes of monocytes and T cells that intensify endothelial damage. In the kidney, these changes eventually lead to crescent formation. Antigen-specific memory T cells persist after disease remission with the potential of reactivation and disease relapse. Although our understanding of the pathophysiologic mechanisms of ANCA-associated vasculitis is far greater now than when ANCAs were first identified in 1982, more experimental work in combination with clinical observations is required to further elucidate these mechanisms.
Article: Systemic vasculitides[Show abstract] [Hide abstract]
ABSTRACT: The vasculitides are a heterogeneous group of diseases that are characterized by blood vessel inflammation and necrosis. They have a wide spectrum of manifestations due to the involvement of arteries and other vessels of various sizes and locations. Classification criteria are useful in improving our understanding of the epidemiology of these conditions but they are not diagnostic criteria. In recent years a progressive increase in incidence has been reported. Both giant cell arteritis and Wegener's granulomatosis are more common in the Northern hemisphere. Environmental factors have been implicated in the pathogenesis of these syndromes. Recent studies in patients with large and small-sized vasculitides support a genetic influence in disease susceptibility. They have confirmed the association of giant cell arteritis and Henoch-Schönlein purpura with HLA-DRB1 alleles. Moreover, the polymorphisms of other genes, such as interleukin-1 receptor antagonist, seem to be implicated in disease severity in patients with cutaneous vasculitis.Bailliè re s Best Practice and Research in Clinical Rheumatology 01/2003; 16(5):833-45. DOI:10.1053/berh.2002.0260 · 3.06 Impact Factor
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ABSTRACT: Anti-neutrophil cytoplasm antibody associated vasculitides are autoimmune diseases that require treatment with powerful immunosuppressants in order to avert life threatening complications, principally renal failure and lung haemorrhage. Their pathogenesis remains unclear but the circulating autoantibodies are almost certainly instrumental in mediating vascular inflammation. Recent insights into leukocyte-autoantibody interactions support this assertion and may direct future therapeutic strategies, perhaps circumventing some of the toxicity associated with currently used drugs.The International Journal of Biochemistry & Cell Biology 04/2003; 35(3):277-82. DOI:10.1016/S1357-2725(02)00094-8 · 4.24 Impact Factor
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ABSTRACT: To assess the epidemiology of the primary systemic vasculitides (PSV) in a well-defined population of southern Europe over a 14-year period using the Chapel Hill Consensus Conference (CHCC) definitions. The case records of all patients 15 years or older with vasculitis diagnosed between January 1988 and December 2001 at a single reference hospital in the Lugo region of northwest Spain were reviewed. Incidence rates were age- and sex-adjusted to the European standard population. Patients were classified as having PSV according to the CHCC definitions. Fifty-four Lugo residents (29 men) fulfilled the CHCC definitions for PSV. The mean age was 60.7 +/- 13.5 years (men: 61.0 +/- 13.4; women: 60.4 +/- 13.8 years). The overall annual incidence of PSV was 13.07/million (95% confidence interval [95% CI] 8.89-19.22). PSV were slightly more common in men. The age-specific incidence showed a clear increase with age. A peak in the 55-64 year age group for the whole group of patients with PSV was observed (34.9/million; 95% CI 28.6-42.6). Nonrandom periodical peaks of incidence every 3 years were only observed when the group of PSV was considered as a whole (P = 0.040). The annual incidence was 2.95/million (95% CI 1.44-6.05) for Wegener's granulomatosis (WG) and 7.91/million (95% CI 4.74-13.20) for microscopic polyangiitis (MPA) (P = 0.035). None of the patients with Churg Strauss syndrome (n = 4) lived in a rural area. Our observations support an increasing incidence of PSV with age. In patients from northwest Spain defined by the CHCC definitions, MPA is more common than WG.Arthritis & Rheumatology 06/2003; 49(3):388-93. DOI:10.1002/art.11115 · 7.87 Impact Factor