The GBM test is a chemiluminescent immunoassay (CLIA), for use on IDS automated analyzers. It is used for the quantitative determination of the specific IgG antibodies directed against the Glomerular Basement Membrane (GBM), in human samples of serum or plasma (EDTA, sodium citrate).

The anti-glomerular basement membrane (anti-GBM) antibodies are the serologic markers for a rare autoimmune disease presenting clinically with rapidly progressive glomerulonephritis and, histologically, with extra-capillary necrotizing glomerulonephritis with a linear immunofluorescence profile (anti-GBM antibody-induced glomerulonephritis). When the lungs are also involved (hemorrhagic alveolitis), the disease takes the name Goodpasture’s syndrome (GP).1

The pathogenic role of the antibodies has been determined with certainty; the tissue damage is mediated by bonding of the anti-GBM antibodies to the glomerular (and alveolar) basement membrane.2

The target auto-antigen has been identified in the non-collagenous globular domain (NC1) on the α3 chain of Type IV collagen, which is present only in the basement membranes of the kidneys, lungs, cochlea, and eye.3

Goodpasture’s syndrome is a very severe disease which, if not quickly and adequately treated, can often take a very rapid course.4 Despite progress in treatment, the survival of the patient and the organ still depend heavily on the degree of kidney damage with which the patient presents; for this reason, early diagnosis is essential for patient survival and recovery of renal function.

Diagnosis of anti-GBM antibody disease or GP is based on detection, via direct immunofluorescence assay of biopsied kidney tissue, of linear deposits of immunoglobulins on the glomerular basement membrane. Since in many cases a kidney biopsy cannot be performed or must be postponed, serologic diagnosis assumes fundamental importance. Circulating anti-GBMs can be detected in primate kidneys by indirect immunofluorescence assay, although the method presents a high specificity but inadequate sensitivity.5 Quantitative, antigen-specific immunometric methods, based on ELISA, fluoroimmunoenzymatic (FLEA), and chemilumenescence (CLIA) assay methods, which make use of whole solubilized GBM, the α3(IV) collagen chain, and, more recently, the GP antigen in human recombinant form, are now available.6 The diagnostic sensitivity of the antigen-specific tests is very high, between 94.7% and 100%, and the specificity toward pathological controls varies between 90.9% and 100%.6 Very recent data confirm the fact that despite the excellent diagnostic performance of these methods, circulating antibodies are not detectable in 5% ca. of patients affected with anti-GBM antibody induced diseases / Goodpasture’s syndrome.7

Given its good clinical significance and high predictive values, anti-GBM antibody assay is indicated for diagnosis of patients whose clinical profiles reveal kidney failure of unknown origin with microscopic hematuria, especially in rapidly progressive cases.

The titer of circulating anti-GBM antibodies is of utility in determining the prognosis.8

Anti-GBM antibodies can be detected in about one-third of patients with a kidney-lung syndrome.

The anti-GBM antibodies are directly responsible for organ damage; monitoring these antibodies is therefore considered very useful for guiding treatment in general and plasmapheresis in particular. Persisting negativity for anti-GBM antibodies is indispensible in prospective kidney transplant patients, since the absence of anti-GBM antibodies reduces the risk that the disease may re-present in the implanted organ.

Since ANCA-associated systemic vasculitides can present with a clinical picture of rapidly progressive glomerulonephritis, it is worthwhile running ANCA assays at the same time as anti-GBM assays. It must be remembered that a significant percentage of patients showing anti-GBMs (10-38%) also show ANCAs, generally with specificity for myeloperoxidases (ANCA-MPO); the clinical significance of this association is not yet clear.6,9,10 A GNRP presentation may sometimes be secondary to systemic connective tissue disease or infections.

Regarding the diagnostic utility of the laboratory datum, it is worthwhile noting that the positive and negative predictive values (PPV, NPV) depend, besides on the sensitivity and the specificity of the test, on the prevalence of the disease in the study population. An appropriate requirement (high pre-testing probability) permits obtaining a result with real clinical utility and significantly reduces the incidence of false positive results.

  1. Salama AD, Levy JB, Lightstone, Pusey CD. Goodpasture’s disease. Lancet 2001; 358: 917-20.
  1. Lerner RA, Glassock RJ, Dixon FJ, The role of anti-glomerular basement membrane antibody in the pathogenesis of human glomerulonephritis. J Exp Med 1967; 126: 989-1004.
  1. Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG. Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen. N Engl J Med 2003; 348: 2543-56.
  1. Levy JB, Turner AN, Rees AJ, Pusey CD. Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma-exchange and immunosuppression. Ann Int Med 2001; 134: 1033-42.
  1. Wilson CB, Dixon FJ. Diagnosis of immunopathologic renal disease. Kidney Int 1974; 5: 389-401.
  1. Sinico RA, Radice A, Corace C, Sabadini E. Anti-glomerular basement membrane antibodies in the diagnosis of Goodpasture syndrome: a comparison of different assays. Nephrol Dial Transplant 2006; 21: 397-401.
  1. Mahler M, Radice A, Sinico RA, Damoiseaux J, Seaman A, Buckmelter K et al. Performance evaluation of a novel chemiluminescence assay for detection of anti-GBM antibodies: an International multicenter study. Nephrol Dial Transplant 2012; 27 (1): 243-52.
  1. Segelmark M, Hellmark T, Wieslander J. The prognostic significance in Goodpasture’s disease of specificity, titre and affinity of anti-glomerular-basement membrane antibodies. Nephron Clin Pract 2003; 94: 59-68.
  1. Hellmark T, Niles JL, Collins AB, McCluskey RT, Brunmark C. Comparison of anti-GBM antibodies in sera with or without ANCA. J Am Soc Nephrol 1997; 8: 376-85.
  1. Levy JB, Hammad T, Coulthart A, Dougan T, Pusey CD. Clinical feature and outcome of patients with both ANCA and anti-GBM antibodies. Kidney Int 2004; 66: 1535-40.