Long-Term Outcome of Anti–Glomerular Basement Membrane Antibody Disease Treated with Plasma Exchange and Immunosuppression

Levy, Jeremy; Turner, Neil; Rees, Andrew J.; Pusey, Charles D.

doi:10.7326/0003-4819-134-11-200106050-00009

Cited by 544 publications

(436 citation statements)

References 19 publications

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“…[19][20][21][22][23][24][25][26] Therefore, in the past few years, Goodpasture syndrome has emerged as a classic autoimmune vascular disease mediated by B cells [27][28][29] and T cells, [19][20][21][22][23][24][25][26] and immunosuppression in conjunction with plasmapheresis remains the most effective therapy. 30 Since the vast majority of autoantibodies bind to the immunodominant epitope E A and epitope E B , several studies have sought to elucidate the key residues in these sites. Such studies have been primarily focused on epitope E A because this site is capable of inducing disease in rodents.…”

Section: Introductionmentioning

confidence: 99%

Zebrafish to humans: evolution of the 3-chain of type IV collagen and emergence of the autoimmune epitopes associated with Goodpasture syndrome

MacDonald

Sund

Grant

et al. 2006

Blood

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Goodpasture syndrome is an autoimmune vascular disease associated with kidney and lung failure, with pathogenic circulating autoantibodies targeted to a set of discontinuous epitope sequences within the noncollagenous domain-1 (NC1) of the ␣3 chain of type IV collagen (␣3(IV)NC1), the Goodpasture autoantigen. We demonstrate that basement membrane extracted NC1 domain preparations from Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio do not bind Goodpasture autoantibodies, while Xenopus laevis, chicken, mouse and human ␣3(IV)NC1 domains bind autoantibodies. The ␣3(IV) chain is not present in C elegans and Drosophila melanogaster, but is first detected in the Danio rerio. Interestingly, native Danio rerio ␣3(IV)NC1 does not bind Goodpasture autoantibodies. Next, we cloned, sequenced, and generated recombinant Danio rerio ␣3(IV)NC1 domain. In contrast to recombinant human ␣3(IV)NC1 domain, there was complete absence of autoantibody binding to recombinant Danio rerio ␣3(IV)NC1. Three-dimensional molecular modeling from existing x-ray coordinates of human NC1 domain suggest that evolutionary alteration of electrostatic charge and polarity due to the emergence of critical serine, aspartic acid, and lysine residues, accompanied by the loss of asparagine and glutamine, contributes to the emergence of the 2 major Goodpasture epitopes on the human ␣3(IV)NC1 domain, as it evolved from the Danio rerio over 450 million years. (Blood. 2006;107: 1908-1915

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Section: Introductionmentioning

confidence: 99%

Zebrafish to humans: evolution of the 3-chain of type IV collagen and emergence of the autoimmune epitopes associated with Goodpasture syndrome

MacDonald

Sund

Grant

et al. 2006

Blood

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“…Antibody levels were 71 to 84% lower after the first IAS treatment and were within normal range after 2 -9 treatments (49). Long-term patient and kidney survival was reported to be 90% and 50% respectively at a mean of 84 months, somewhat better than previous reports using plasma exchange and immunosuppression but not comparable to larger patient cohorts (43). Therefore, IAS offers an effective therapy for direct removal of circulating anti-GBM antibodies and is non-inferior to plasma exchange although this needs to be more thoroughly evaluated.…”

Section: Management Antibody Removalmentioning

confidence: 76%

“…A treatment regimen historically established by the Hammersmith group remains at the forefront of therapy (Table 1). Prednisolone (1mg/kg tapered over 6-9 months) and cyclophosphamide for 2 -3 months are used in combination with daily plasmapheresis for 14 days, or until the anti-GBM antibody is no longer detectable (3,43). This approach has transformed patient and kidney survival.…”

Section: Management Antibody Removalmentioning

confidence: 99%

Diagnostic and management challenges in Goodpasture’s (anti-glomerular basement membrane) disease

Henderson

Salama

2017

Nephrology Dialysis Transplantation

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Goodpasture's or anti-glomerular basement membrane (GBM) disease is classically characterised by the presence of circulating autoantibodies directed against the non-collagenous domain of the 3 chain of type IV collagen(3(IV)NC1), targeting glomerular and alveolar basement membranes, and associated with rapidly progressive crescentic glomerulonephritis, with alveolar haemorrhage in over half the patients. However, there are increasing examples of variants or atypical presentations of this disease, and proposed novel therapeutic options, which nephrologists should be aware of. The pathophysiology of this condition has been understood through molecular analysis of the antibody-antigen interactions and the use of HLA-transgenic animals, while the association of anti-GBM antibodies with anti-neutrophil cytoplasm antibodies (ANCA) and their combined impact on disease phenotype is increasingly recognised, providing some insights into the basis of glomerular damage and autoimmunity.

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“…10 With current therapeutic strategies, the 1-year survival rate for anti-GBM disease is around 77%, with a wide range from 65% to 100%, depending on the severity of disease and renal function on presentation. 11 However, renal recovery is less common and depends on renal function at the initiation of therapy. In a British study of 71 patients with anti-GBM disease, 11 those who presented with a serum creatinine concentration of less than 5.7 mg/dL had a 95% chance of retaining independent renal function at 1-year follow-up.…”

Section: Discussionmentioning

confidence: 99%

“…11 However, renal recovery is less common and depends on renal function at the initiation of therapy. In a British study of 71 patients with anti-GBM disease, 11 those who presented with a serum creatinine concentration of less than 5.7 mg/dL had a 95% chance of retaining independent renal function at 1-year follow-up. This percentage dropped to 82% in patients who presented with a serum creatinine concentration of more than 5.7 mg/dL but who did not require dialysis immediately.…”

Section: Discussionmentioning

confidence: 99%

65-Year-Old Woman With Shortness of Breath and Dark Urine

Lim

Greene

2011

Mayo Clinic Proceedings

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A 65-year-old previously healthy woman presented to her primary care physician with a 6-week history of increasing dyspnea, accompanied by a dry cough, fatigue, malaise, and poor appetite. Before her initial presentation and the onset of the aforementioned symptoms, she had attributed her illness to an upper respiratory tract infection. She also reported a 1-week history of passing dark urine and had been treated empirically 2 weeks previously with a 3-day course of oral trimethoprim-sulfamethoxazole for presumptive urinary tract infection. At the time of presentation, she denied any other constitutional symptoms, recent travel, medication changes (except for the trimethoprim-sulfamethoxazole), and animal or occupational exposure. Her medical history was remarkable for hypertension, hypothyroidism, diverticulosis, and peptic stricture in the gastroesophageal junction status after a balloon dilatation. Initial laboratory studies yielded the following results (reference ranges provided parenthetically for abnormal values): hemoglobin, 8.4 g/dL (12.0-15.5 g/dL); leukocytes, 12.3 × 10 9 /L (3.5-10.5 × 10 9 /L); platelet count, 449 × 10 9 /L; prothrombin time, 12.5 s (8.3-10.8 s); serum sodium, 131 mmol/L (135-145 mmol/L); potassium, 3.9 mmol/L; creatinine, 4.8 mg/dL (0.6-1.1 mg/dL); blood urea nitrogen, 56 mg/ dL (6-21 mg/dL); chloride, 95 mmol/L (100-108 mmol/L); bicarbonate, 23 mEq/L; calcium, 9.6 mg/dL; and glucose, 97 mg/dL. Findings on liver function tests were as follows: aspartate aminotransferase, 29 IU/L; alanine aminotransferase, 21 IU/L; total and direct bilirubin, 0.2 mg/dL and 0.1 mg/dL, respectively; albumin, 3.5 g/dL; and total protein, 6.6 g/dL.Because previous serum creatinine values had been in the normal range, the patient was admitted to her local hospital for further work-up for acute renal failure. On admission she was hemodynamically stable and her vital signs were as follows: blood pressure, 134/78 mm Hg; heart rate, 70 beats/min; and respiratory rate, 22 breaths/min on room air. On physical examination, the patient was afebrile, alert, and oriented. There was mild conjunctival pallor. Cardiac examination revealed a normal S 1 and S 2 with a 2/6 holosystolic nonradiating murmur loudest at the apex, no additional rubs, and no jugular venous distension. Lungs were clear to auscultation except for bibasilar inspiratory crackles. The remainder of the physical examination findings were unremarkable. Chest radiography showed mild cardiomegaly, pulmonary venous hypertension, and small bilateral pleural effusions with bibasilar atelectasis.A urinalysis demonstrated 4 to 10 white blood cells per high-power field (hpf) (1-10/ hpf) and 51 to 100 red blood cells (RBCs)/hpf (<3/hpf), with less than 25% noted to be dysmorphic, accompanied by occasional granular casts. The predicted urinary protein value was 3281 mg/24 hours. The urine sample was orange and cloudy.

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Long-Term Outcome of Anti–Glomerular Basement Membrane Antibody Disease Treated with Plasma Exchange and Immunosuppression

Abstract: Patients with the Goodpasture syndrome and severe renal failure should be considered for urgent immunosuppression therapy, including plasma exchange, to maximize the chance of renal recovery. Patients needing immediate dialysis are less likely to recover.

Cited by 544 publications

References 19 publications

Zebrafish to humans: evolution of the 3-chain of type IV collagen and emergence of the autoimmune epitopes associated with Goodpasture syndrome

Zebrafish to humans: evolution of the 3-chain of type IV collagen and emergence of the autoimmune epitopes associated with Goodpasture syndrome

Diagnostic and management challenges in Goodpasture’s (anti-glomerular basement membrane) disease

65-Year-Old Woman With Shortness of Breath and Dark Urine

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