Monday, June 3, 2019

Features of Goodpastures Syndrome

Features of Goodpastures SyndromeIntroductionGoodpastures syndrome, a rare autoimmune sickness is characterized by anti-GBM (anti-glomerular basement tissue layer) antibodies attacking glomerular and dental consonant basement membranes of the kidneys and lungs respectively. It was first reported by Dr. Ernest William Goodpasture in 1919 and first used by Stanton and Tange in 1957 in their case studies involving nine patients with the pulmonary-renal syndrome. 1, 2Clinical Features The onset of this malady ranges from the ages of 20-30 and 60-70 especially in young men in their late twenties or in men and women over sixty years of age study. 3The diagnostic techniques involved in detection of Goodpastures syndrome include i) urine analysis that detects kidney damage by presence of high number of red blood cells or protein in the urine take ii) blood tests showing the presence of anti-GBM antibodies iii) x-rays that can show anomalies in lung anatomy or iv) biopsies that involve im aging of a kidney tissue sample to demonstrate glomeruli characterised by crescent-shaped structures and lines of antibodies attached to the GBM. 4While Goodpastures syndrome constitutes the representation of clinical features like rapidly progressive glomerulonephritis (RPGN) and pulmonary hemorrhage from any cause, Goodpasture disease similarly includes the presence of anti-GBM antibodies in addition to the other characteristics. The term anti-GBM disease constitutes a patient with the typical autoantibodies, irrespective of clinical symptoms and characteristic features. 1,5The clinical manifestations associated with Goodpastures syndrome include stabbing renal failure resulting from rapidly progressive glomerulonephritis along with pulmonary hemorrhage that might prove fatal. The symptoms in relation to it consist of bleeding of lungs, kidney failure, hematuria, proteinuria, general malaise, fatigue, and incubus loss. 1,6,7,8,9The exact etiology of this syndrome is not known h owever there seem to be genetic and environmental risk factors. The factors beingness i) exposure to organic solvents or hydrocarbons ii) smoking and drugs iii) infection iv) exposure to metal particulate matter v) lymphocyte-depletion therapy. 1,5,10The characteristic pathology in individuals experiencing the Goodpastures Syndrome can be detected by immunofluorescence staining technique of the immunoglobulin G on the GBM that shows smooth diffuse linear patterns. 11Hemodialysis, plasma exchange, cyclophosphamide drugs and immunosuppressive agents like methylprednisolone pulse therapy or oral administration of prednisolone are possible treatments for Goodpastures syndrome. 12,13,14 raw material Cellular and Molecular MechanismsThe localization of immunoglobulin IgG deposits at sites of inflammation within the pulmonary and renal basement membranes shows Goodpastures syndrome (a take a leak of the anti-GBM disease) to be an antibody-mediated autoimmune disease. The unhealthful rol e of these antibodies has been confirmed bytransplantation of circulating or kidney-eluted anti-GBM antibodies to Rhesus monkey or human kidney allografts that result in the development of the disease.A lineament II hypersensitivity reaction occurs when antibodies are targeted against extracellular matrix (ECM) specific antigens. 15The hypersensitivity response affects all organs in the body of which collagen is a constituent but the dental and glomerular basement membranes are more prone to the effect. This discrepancy is a result of increased accessibility of epitopes (antigen molecules facilitating attachment to a matching antibody) linked to overexpression of 3 collagen chains in the respective basement membranes allowing access and formation of antibodies. 16While 3NC1 antibodies are the most common in patients with Goodpastures syndrome, 5NC1 antibodies are less prevalent. Sometimes antineutrophil cytoplasmic antibody ANCA can also be present. 5,17The disorder develops ant ibodies that target 3 chain of basement membrane collagen (type IV collagen) present in alveoli in lungs and in the glomeruli that form the filtering units of the kidneys within the nephrons. These structures contain the basement membrane with collagen as its essential component that differentiates the epithelia from the underlying tissue. The conformational epitopes of the Goodpasture antigen are localized within 2 regions in the carboxyl terminal, noncollagenous (NC1) landing field of a type IV collagen chain, 3(IV)NC1. 1, 5, 18. Upon interaction of the anti-GBM antibodies with the conformational epitope of the GBM glycoproteins, the attendant pathway of the immune system gets activated. This results in infiltration by polymorphonuclear leukocytes (PMNs) and monocytes. The severely damaged GBM induces reflux of fibrinogen into the Bowman space, fibrinogen polymerizes to fibrin through the proliferation of procoagulant factors from activated monocytes, lead story to a crescent formation.19Goodpastures syndrome is linked with specific HLA types. Both positive (HLA-DR15) and negative (HLA-DR7) associations are defined and being used to develop an understanding of antigen presentation, tolerance and autoimmunity. 20,21,22Recent DevelopmentsRecent developments like the plasmapheresis technique, steroidal drugs, and immunosuppressive therapy have drastically ameliorated the course of the medical condition in comparison to yesteryears, in which Goodpasture syndrome was deemed fatal. 23Zhao et al., demonstrate the significant role of 5NC1-specific antibodies in pathogenesis of Goodpastures disease and also re-confirm 345 collagen IV molecule as the original GP autoantigen. 17The invention of a drug, now patented, with its active element containing boronthat constitutes inhibitors of arginase activity has claimed remedial effects in the pathological state of Goodpastures Syndrome. 24A recently developed, patented prophylaxis for glomerulonephritis resulting from Goodpastures syndrome comprises of administration of a therapeutically effective amount of an IL-6 antibody that binds with or regulates the expression or activity of a mammalian IL-6 polypeptide. 25ConclusionsGoodpastures Syndrome is an autoimmune disease characterized by anti-GBM antibodies attacking glomerular and dental basement membranes. The innate immune response comprises of (i) cell death (ii) polymorphonuclear cell releasing neutrophils, basophils, eosinophils, antigens and monocytes to infiltrate the glomerulus. The adaptive immune response triggers the classical pathway of complement activated by antigen-antibody complex formation, and type II hypersensitivity reaction. Here antigens are targeted against cell- specific and tissue specific antigens (chiefly the connective tissue).Unanswered QuestionsCurrently, there is a mickle of research focusing on deciphering the causative agents of the harmful antibodies that lead to the development of Goodpastures syndrome. Eviden ce from this research can lead to novel drug discovery, eventually leading to a potential definitive cure for Goodpastures syndrome. 17The exact the genetic determinants that constitute the etiology of Goodpastures syndrome are yet to be found.BibliographySalama AD, Pusey CD. 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