Anti-GBM Antibody Disease Clinical Presentation

Updated: Dec 19, 2019
  • Author: Agnieszka Swiatecka-Urban, MD, FASN, FAAP; Chief Editor: Craig B Langman, MD  more...
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Presentation

History

Anti–glomerular basement membrane (anti-GBM) antibody disease can occur year-round, but the incidence increases in the spring and in early summer. Most patients present with features of systemic illness and either acute nephritis or pulmonary involvement; a subset may have all 3 findings. Pulmonary involvement can precede the onset of glomerulonephritis by several years, or it can develop after renal disease is evident.

  • Symptoms of systemic illness include low-grade fever, malaise, headache, anorexia, nausea, vomiting, weight loss, and fatigue.

  • Symptoms of renal involvement include hematuria, oliguria, and edema.

  • Symptoms of pulmonary involvement include shortness of breath, cough, and expectoration of material that ranges from blood-streaked sputum to massive hemoptysis. A feeling of warmth inside the chest may precede hemoptysis.

  • Approximately 30% of patients with Goodpasture syndrome are antineutrophilic cytoplasmic antibody (ANCA) positive some time during the illness. Such patients may present with pruritic skin rashes and arthralgia.

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Physical

Physical findings depend on the organ system involved and on the severity of the disease. No abnormalities may be evident in the absence of renal or pulmonary involvement.

  • Signs of renal involvement include the following:

    • When renal involvement is severe, volume overload of the intracellular and extracellular fluid may result in tachycardia, tachypnea, hypertension, pulmonary rales, and pitting edema.

    • Patients with uremia may have a specific breath odor, bruises, pallor, tremor, myoclonus, asterixis, focal neurologic signs, mental status changes, and seizures.

  • Signs of pulmonary involvement include the following:

    • Respiratory distress ranging from mild distress to respiratory failure

    • Pulmonary hemorrhage that may result in pallor, tachycardia, and shock

  • Pulmonary manifestations can precede or follow signs of nephritis.

  • Patients with high ANCA and low anti-GBM antibody titers may present with various vasculitic skin rashes.

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Causes

Anti-GBM disease is an autoimmune condition of known pathogenesis but unclear etiology. However, several factors play a permissive role in disease initiation.

  • Respiratory infections (eg, influenza) or inhaled toxins (eg, hydrocarbons, gasoline vapors, hypercarbic oxygen, tobacco, hairspray) may trigger pulmonary involvement.

  • Factors associated with renal manifestations are renal injury from ischemia, membranous glomerulonephritis, and, possibly, extracorporeal shock-wave lithotripsy. Only 3 cases of anti-GBM disease occurring after lithotripsy have been described, although several million procedures have been performed. Therefore, the number of cases is too small to establish a causative association. However, consider testing for anti-GBM antibodies when patients have declining renal function after lithotripsy.

  • Individuals with Alport syndrome lack the Goodpasture epitopes. The transplantation of a kidney from a healthy donor to a patient with an Alport syndrome introduces the Goodpasture epitopes as neoantigens. Approximately 50% of kidney recipients with Alport syndrome develop anti-GBM antibodies; only a few of these patients have graft failure because of anti-GBM disease.

  • In a review of 118 male patients with the X-linked dominant form of Alport syndrome, anti-GBM glomerulonephritis developed in only 3 (2.5%). [9] All had a large deletion in the COLA4A5 gene. Sixteen other patients with a large rearrangement in COLA4A5 and 32 with a small mutation that was expected to produce a truncated alpha-5 (type IV collagen) protein lacking the NC1 domain did not develop anti-GBM glomerulonephritis in the graft.

  • In some patients, the anti-GBM antibody has immunoblotting characteristics different from those of patients with the primary form of Goodpasture syndrome. These characteristics may result from differences in antigenic expression caused by the interaction of the various alpha chains in the basement membrane. This difference also may explain why the clinical expression of the disease is milder in patients with Alport syndrome than in those with the primary form of Goodpasture syndrome. The low incidence of the syndrome and its mild clinical manifestations make renal transplantation the treatment of choice for patients with Alport syndrome who have end-stage renal disease.

  • Anti-GBM antibody disease has a strong positive association with the HLA-DR15 haplotype, particularly the DRB1*1501 allele, which is found in more that 80% of patients with anti-GBM antibody disease. Furthermore, a strong dominant protection from the disease is associated with the expression of DRB1*0701 such that individuals inheriting DRB1*1501 and DRB1*0701 have no higher risk of disease than does the general population. The DRB1*01 allele offers relatively weak protection.

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