Extraglomerular distribution of immunoreactive Goodpasture antigen

Cashman, S. J.; Pusey, Charles D.; Evans, David J.

doi:10.1002/path.1711550110

Cited by 55 publications

(27 citation statements)

References 23 publications

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“…Deposition of anti-GBM Ab in the choroid plexus has been demonstrated by immunofluorescence studies. 5 Clinical deterioration in our patient occurred in the presence of low anti-GBM Ab levels, as found in previously reported GD patients with central nervous system vasculitis. Little is known about anti-GBM Ab levels in the cerebrospinal fluid and their potential pathophysiological role in the development of central nervous system vasculitis in Goodpasture patients.…”

Section: Discussionsupporting

confidence: 87%

Spinal subarachnoid hematomas and cerebral infarctions in Goodpasture's disease

et al. 2010

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Section: Discussionsupporting

confidence: 87%

Spinal subarachnoid hematomas and cerebral infarctions in Goodpasture's disease

et al. 2010

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“…The principal target of the autoimmune response in anti-GBM disease has been identified as the noncollagenous (NC1) domain of the a3 chain of type IV collagen (a3[IV]NC1; the "Goodpasture autoantigen") (32,33). The clinical pattern of reno-pulmonary disease reflects the restricted expression of this antigen to the basement membranes of glomerular and alveolar capillaries (and to a lesser extent, the retina, choroid plexus, and cochlea, where it is generally not associated with clinical disease [34]). Two principle autoantibody (B cell) epitopes within the autoantigen have been identified, designated EA and EB (35), which in native GBM are usually sequestered within the quaternary structure of the noncollagenous domains of the triple helix of a3, 4, and 5 chains.…”

Section: Immunopathogenesismentioning

confidence: 99%

Anti-Glomerular Basement Membrane Disease

McAdoo¹,

Pusey²

2017

CJASN

314

303

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Anti-glomerular basement membrane (anti-GBM) disease is a rare small vessel vasculitis that affects the capillary beds of the kidneys and lungs. It is an archetypic autoimmune disease, caused by the development of directly pathogenic autoantibodies targeting a well characterized autoantigen expressed in the basement membranes of these organs, although the inciting events that induce the autoimmune response are not fully understood. The recent confirmation of spatial and temporal clustering of cases suggests that environmental factors, including infection, may trigger disease in genetically susceptible individuals. The majority of patients develop widespread glomerular crescent formation, presenting with features of rapidly progressive GN, and 40%-60% will have concurrent alveolar hemorrhage. Treatment aims to rapidly remove pathogenic autoantibody, typically with the use of plasma exchange, along with steroids and cytotoxic therapy to prevent ongoing autoantibody production and tissue inflammation. Retrospective cohort studies suggest that when this combination of treatment is started early, the majority of patients will have good renal outcome, although presentation with oligoanuria, a high proportion of glomerular crescents, or kidney failure requiring dialysis augur badly for renal prognosis. Relapse and recurrent disease after kidney transplantation are both uncommon, although de novo anti-GBM disease after transplantation for Alport syndrome is a recognized phenomenon. Copresentation with other kidney diseases such as ANCAassociated vasculitis and membranous nephropathy seems to occur at a higher frequency than would be expected by chance alone, and in addition atypical presentations of anti-GBM disease are increasingly reported. These observations highlight the need for future work to further delineate the immunopathogenic mechanisms of anti-GBM disease, and how to better refine and improve treatments, particularly for patients presenting with adverse prognostic factors.

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“…Direct immunofluorescence studies to assess deposits of IgG and fibrin within the glomeruli were carried out on kidneys obtained at sacrifice by a method similar to that previously described (40). Tissue was embedded in OCT II embedding medium (Miles Inc., Elkhart, Indiana, USA) on cork discs.…”

Section: Assessment Of Eagmentioning

confidence: 99%