1/19. Rapidly progressive antineutrophil cytoplasm antibodies associated with pulmonary-renal syndrome in a 10-year-old girl.CONTEXT: The term pulmonary-renal syndrome has been used frequently to describe the clinical manifestations of a great number of diseases in which pulmonary hemorrhage and glomerulonephritis coexist. The classic example of this type of vasculitis is Goodpastures syndrome, a term used to describe the association of pulmonary hemorrhage, glomerulonephritis and the presence of circulating antiglomerular basement membrane antibodies (anti-GBM). Among the several types of systemic vasculitides that can present clinical manifestations of the pulmonary-renal syndrome, we focus the discussion on two types more frequently associated with antineutrophil cytoplasm antibodies (ANCA), microscopic polyangiitis and Wegener's granulomatosis, concerning a 10 year old girl with clinical signs and symptoms of pulmonary-renal syndrome, with positive ANCA and rapidly progressive evolution. CASE REPORT: We describe the case of a 10-year-old girl referred to our hospital for evaluation of profound anemia detected in a primary health center. Five days before entry she had experienced malaise, pallor and began to cough up blood-tinged sputum that was at first attributed to dental bleeding. She was admitted to the infirmary with hemoglobin = 4 mg/dL, hematocrit = 14 %, platelets = 260,000, white blood cells = 8300, 74 % segmented, 4 % eosinophils, 19 % lymphocytes and 3 % monocytes. Radiographs of the chest revealed bilateral diffuse interstitial alveolar infiltrates. There was progressive worsening of cough and respiratory distress during the admission day, when she began to cough up large quantities of blood and hematuria was noted. There was rapid and progressive loss of renal function and massive lung hemorrhage. The antineutrophil cytoplasm antibody (ANCA) test with antigen specificity for myeloperoxidase (anti-MPO) was positive and the circulating anti-GBM showed an indeterminate result.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/19. Anti-glomerular basement membrane nephritis and bullous pemphigoid caused by distinct anti-alpha 3(IV)NC1 and anti-BP180 antibodies in a patient with Crohn's disease.BACKGROUND: Anti-glomerular basement membrane (GBM) nephritis is a rare disease induced by antibodies directed against alpha3(IV)NC1, the Goodpasture antigen. We report a patient with Crohn's disease who developed anti-GBM nephritis and the skin blistering disorder bullous pemphigoid, owing to distinct autoantibodies. methods: frozen sections of skin and kidney biopsies were incubated with antisera specific for human IgG, IgA, IgM, fibrin, and C3. Reactivity of the patient's serum with GBM antigens was studied by Western blot using bovine solubilized type IV collagen and by enzyme-linked immunosorbent assays using alpha1(IV), alpha3(IV), and alpha5(IV)NC1 recombinant proteins. Reactivity studies against skin antigens were done by Western blot using human keratinocyte and dermal extracts and three recombinant forms of the bullous pemphigoid antigen180 (BP180, also called BPAG2 or type XVII collagen). The patient's serum was affinity fractionated on a (IV)NC1 column, and the bound and unbound fractions were analyzed for their reactivity against GBM and skin antigens. RESULTS: The patient had deposits of IgG along the GBM and the epidermal basement membrane zone. Circulating IgG antibodies against alpha3(IV)NC1 were detected. The patient's autoantibodies immunoblotted the intracellular domain but not the extracellular domain of BP180. Reactivity of the patient's IgG with BP180 was found only in the unbound fraction of the serum. CONCLUSION: The simultaneous development of a rare renal and skin autoimmune disorder, resulting from non-cross-reactive autoantibodies, suggests that a common triggering event could be responsible for the autoimmune injury.- - - - - - - - - - ranking = 5keywords = antigen (Clic here for more details about this article) |
3/19. Sequential development of perinuclear ANCA-associated vasculitis and anti-glomerular basement membrane glomerulonephritis.A 75-year-old man suffered from perinuclear antineutrophil cytoplasm antibody (p-ANCA)-associated vasculitis with mild renal involvement. Three years later, he suddenly experienced an anuric acute renal failure due to anti-glomerular basement membrane (GBM) disease. Antibodies to myeloperoxydase were continuously present at a high titer in the patient's serum while serum anti-GBM antibodies were only detected at the time of the acute renal failure. A substantial proportion of patients with anti-GBM glomerulonephritis simultaneously display ANCAs whose pathogenic role is not clear. In our case, ANCAs were supposed to be of pathogenic importance because they may have uncovered the Goodpasture antigen. This case report lends further support to the concept that p-ANCA vasculitis may trigger anti-GBM disease.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
4/19. Pregnancy complicated by Goodpasture syndrome.Goodpasture syndrome is characterized by pulmonary hemorrhage, glomerulonephritis, and an autoantibody to glomerular basement membrane antigens. Current management of this potentially lethal disease consists of glucocorticoids to control pulmonary hemorrhage, cytotoxic drugs to inhibit further renal damage, and plasma exchange to clear circulating anti-basement membrane antibodies. These treatment modalities pose difficult management issues during pregnancy. We describe a successful pregnancy outcome in a parturient with Goodpasture syndrome. Antepartum care included serial pulmonary and renal evaluations. In patients without disease progression, a favorable outcome may be possible.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
5/19. Recurrent Goodpasture's disease secondary to a monoclonal IgA1-kappa antibody autoreactive with the alpha1/alpha2 chains of type IV collagen.Goodpasture's disease is characterized by crescentic glomerulonephritis and lung hemorrhage in the presence of anti-glomerular basement membrane (anti-GBM) antibodies. This disease usually is mediated by IgG autoantibodies directed against the noncollagenous domain of the alpha3(IV) collagen chain, the Goodpasture autoantigen. In rare cases, anti-GBM antibodies of IgA or IgM class are involved, but their specificity has not been determined, and their target antigen remains unknown. The authors present the case of a 62-year-old man with anti-GBM disease mediated by a monoclonal IgA-kappa antibody, which progressed to end-stage renal disease despite intensive immunosuppression. The patient underwent living-related kidney transplantation, but lung hemorrhage and crescentic glomerulonephritis recurred, causing the loss of the allograft 2 years later. Indirect immunofluorescence found the presence of circulating IgA antibodies reactive with a basement membrane component, identified by enzyme-linked immunoabsorbent assay and Western blot as the alpha1/alpha2(IV) collagen chains. Sensitivity to digestion with collagenase indicated that IgA bound to epitopes located in the collagenous domain. This is the first case of recurrent Goodpasture's disease secondary to an autoreactive IgA antibody. The specificity of an IgA antibody implicated in the pathogenesis of anti-GBM disease has been investigated for the first time, identifying the alpha1/alpha2(IV) collagen chains as a novel target for nephritogenic antibodies.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
6/19. An unusual case of pulmonary-renal syndrome associated with defects in type IV collagen composition and anti-glomerular basement membrane autoantibodies.Commercial serological assays for the presence of anti-glomerular basement membrane (GBM) antibodies are thought to be indicative of Goodpasture's syndrome. We report a case in which commercial tests inaccurately suggested that a patient with a pulmonary-renal syndrome had Goodpasture's disease. Additional laboratory testing using recombinant type IV collagen NC1 domain proteins showed that the autoantibodies in question were not directed against the Goodpasture antigen (the alpha3NC1 domain), but against the alpha2NC1 domain of type IV collagen. Our findings represent the first known case of human autoantibodies to the alpha2NC1 domain. Further investigation showed that this patient has decreased alpha3 and alpha5 chain expression in the GBM and defects in type IV collagen, resembling abnormalities in patients with Alport's syndrome.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
7/19. Distinct epitopes for anti-glomerular basement membrane alport alloantibodies and goodpasture autoantibodies within the noncollagenous domain of alpha3(IV) collagen: a janus-faced antigen.Alport posttransplantation anti-glomerular basement membrane (GBM) nephritis is mediated by alloantibodies against the noncollagenous (NC1) domains of the alpha3alpha4alpha5(IV) collagen network, which is present in the GBM of the allograft but absent from Alport kidneys. The specificity of kidney-bound anti-GBM alloantibodies from a patient who had autosomal recessive Alport syndrome (ARAS) and developed posttransplantation nephritis was compared with that of Goodpasture autoantibodies from patients with autoimmune anti-GBM disease. Allograft-eluted alloantibodies reacted specifically with alpha3alpha4alpha5 NC1 hexamers, targeting their alpha3NC1 and alpha4NC1 subunits, and recognized a noncontiguous alloepitope formed jointly by the E(A) and E(B) regions of alpha3NC1 domain. In contrast, human Goodpasture autoantibodies recognized the separate E(A) and E(B) autoepitopes of alpha3NC1 but not the composite alloepitope. Molecular modeling of alpha3NC1 revealed that the alloepitope is more accessible within the NC1 hexamers than the partially sequestered Goodpasture autoepitopes. overall, the specificity of alloantibodies indicated a selective lack of immune tolerance toward the alpha3 and alpha4(IV) collagen chains not expressed in patients with ARAS. Using COL4A3 knockout mice, a model of ARAS, it was shown further that acid-dissociated rather than native alpha3alpha4alpha5 NC1 hexamers elicited murine anti-GBM antibodies most closely resembling human ARAS alloantibodies. In contrast, alpha3NC1 monomers elicited Goodpasture-like murine antibodies, targeting the E(A) and E(B) autoepitopes. Thus, the identity of alpha3NC1 epitopes targeted by anti-GBM antibodies is strongly influenced by the molecular organization of the immunogen. These findings suggest that different isoforms of alpha3(IV) collagen may be implicated in the pathogenesis of ARAS posttransplantation anti-GBM nephritis and Goodpasture disease.- - - - - - - - - - ranking = 4keywords = antigen (Clic here for more details about this article) |
8/19. Concurrent anti-glomerular basement membrane disease and membranous glomerulonephritis: a case report and literature review.BACKGROUND: anti-glomerular basement membrane disease (anti-GBM) is a relatively rare entity characterized by antibodies to collagen type iv of glomerular and alveolar basement membranes. The sequential or simultaneous presentation of anti-glomerular basement membrane disease with membranous glomerulonephritis has been infrequently described. CASE: We present the case of a 49-year-old man who had fatigue, flank pain, hematuria and renal failure. serology was positive for anti-GBM antibodies; crescentic glomerulonephritis was seen on renal biopsy. Immunofluorescence and electron microscopy demonstrated evidence of both anti-GBM glomerulonephritis and membranous deposits. DISCUSSION: Simultaneous anti-GBM disease and membranous glomerulonephritis is the most common temporal presentation of this rare entity. However, cases of membranous glomerulonephritis preceding or following recovery from anti-GBM disease have been described. Study of such cases provides insight into pathophysiologic mechanisms, including the possibility of increased antigen synthesis, exposure of cryptic epitopes, and/or capping and shedding of antigen-antibody complexes, in analogy to Heymann nephritis.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
9/19. The uncertain significance of anti-glomerular basement membrane antibody among hiv-infected persons with kidney disease.Glomerular lesions that complicate patients with human immunodeficiency virus (hiv) infection include hiv-associated nephropathy, membranous glomerulopathy, and immune-complex glomerulonephritides. This case series presents 3 patients with clinically significant renal disease and positive test results for anti-glomerular basement membrane (anti-GBM) antigen. Characteristic histological findings that would suggest anti-GBM antibodies have a significant role in the pathological state of each patient's kidney disease were absent. In addition, each patient recovered without specific treatment for anti-GBM disease. This case series suggests that anti-GBM antibodies likely are related to the B-cell expansion previously described in patients with hiv infection. We propose that clinicians interpret results of anti-GBM antibody tests carefully for patients with hiv infection, considering biopsy before empiric therapy, particularly in a clinical presentation that is atypical for Goodpasture disease.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
10/19. Characterization of the NC1 domain of collagen type iv in glomerular basement membranes (GBM) and of antibodies to GBM in a patient with anti-GBM nephritis.Anti-glomerular basement membrane (GBM) nephritis is associated with production of antibodies to the Goodpasture antigen (GPA) component of the NC1 domain of collagen type iv. We studied a patient with anti-GBM nephritis with regard to 1) reactivity of the anti-GBM antibodies in his serum, plasmapheresis fluid (PPF), and an eluate prepared from GBM of his nephrectomy specimen, and 2) electrophoretic and immunologic properties of the NC1 domain extracted by collagenase digestion from GBM of his nephrectomy specimen. Antibodies to different NC1 determinants in serum, PPF and eluate were detected by immunofluorescence of glomerular capillaries of normal kidney. In addition, the antibody in PPF, but not in the eluate, reacted strongly in a plate-binding radioimmunoassay with NC1 domain extracted from normal human GBM, and bound by Western blotting to both dimer (46 kD and 49 kD) and monomer (24 kD, 26 kD and 28 kD) components of the NC1 domain. Analysis of the NC1 domain in the patient's GBM by SDS-PAGE showed a number of abnormalities, including an absence of monomer bands. Moreover, there was diminished reactivity of the patient's NC1 domain by the radioimmunoassay and Western blotting, using his PPF and a rabbit anti-NC1 antiserum. These findings indicated that there were different types of antibodies to NC1 domain in PPF and eluate, associated with an abnormal NC1 domain in GBM. These results have allowed us to speculate on the pathogenesis of anti-GBM nephritis in this patient.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
| | Next -> |