Goodpasture syndrome is characterised by lung haemorrhage, renal failure and the presence of anti-GBM antibodies. As there are several other autoimmune diseases which may present with similar symptoms, this kit is a useful aid in differentiation between these diseases.
Background
Goodpasture syndrome is characterised by lung haemorrhage, renal failure and the presence of anti-GBM antibodies. Diagnosis is based on clinical signs of lung hemorrhage and rapidly progressive glomerulonephritis combined with findings of anti-GBM antibodies.
As there are several other autoimmune diseases which may present with similar symptoms, this kit is a useful aid in differentiation between these diseases.
Less than one third of patients with reno-pulmonary syndromes have antibodies against the Goodpasture antigen, the majority having either Proteinase 3-ANCA or Myeloperoxidase-ANCA.
Historically, indirect immunofluorescence was used to detect anti-GBM antibodies. When the first ELISA based on a collagenase digest was published in 1981, assays using crude extracts were the only alternative. In 1984 the specific antigen was shown to derive from the C-terminal domain of type IV collagen (alpha 3 chain) and sensitive and specific assays were subsequently developed. The antigen is characterised by a restricted tissue distribution occurring mainly in kidney and lungs.
The sensitivity and specificity of ELISA to detect anti-GBM antibodies is high. False positive reactions occur, mainly in SLE and other diseases with polyclonal activation, most of which yield low titers of 10-20 U/ml.
Clinical Significance
While Goodpasture’s syndrome is a relatively rare condition, the disease is rapidly progressive and, unless treated, has a high case-fatality rate. Immediate and correct treatment is necessary before kidney (and often lung) damage has progressed too far. In clinical practice the diagnosis and recognition of the disease is frequently delayed since it is unexpected. Clinical signs such as hemoptysis, precipitate anemia, pulmonary opacities at x-ray and/or oliguria are in a sense unspecific and common to a variety of disorders. Mild prodromal lung or kidney symptoms are often overlooked or masked by a precipitating infection.
The problems of diagnosing crescentic glomerulonephritis and the importance of rapidly initiating selective treatment based on this diagnosis are generally recognized.
Biochemical studies have shown that the antigen involved in Goodpasture’s syndrome is a part of the globular domain of the collagen IV chains in the GBM. Upon dissociation the reactive epitope has been assigned to a peptide termed M2, consisting of the a3 chain of collagen IV. With this in mind, this antigen has been purified and used for the assay of autoantibodies by enzyme-linked immunosorbent assay (ELISA).
Dammacco F, Battaglia S, Gesualdo L, Racanelli V. Goodpasture's
disease: A report of ten cases and a review of the literature.
Autoimmunity Reviews 2013; 12: 1101–1108
Hellmark T, Segelmark M. Diagnosis and classification of Goodpasture’s
disease (anti-GBM). Journal of Autoimmunity 2014;48-49: 108-112
Technical information
The wells of the microtitre strips are coated with purified GBM antigen (alfa 3 chain). During the first incubation, specific antibodies in diluted serum, will bind to the antigen coating.
The wells are then washed to remove unbound antibodies and other components.
A conjugate of alkaline phosphatase-labelled antibodies to human IgG binds to the antibodies in the wells in this second incubation.
After a further washing step, detection of specific antibodies is obtained by incubation with substrate solution. The amount of bound antibodies correlates to the colour intensity and is measured in terms of absorbance (optical density (OD)). The absorbance is then calculated against a calibrator curve and the results are given in arbitrary U/ml.
