Background/Purpose: Anti-GBM disease is characterized by rapidly progressive glomerular nephritis with or without pulmonary hemorrhage.  It is usually monophasic in nature and disease severity correlates with antibody titer.  The disease is mediated by pathogenic antibodies directed against the non-collagenous region of the α3 chain of type IV collagen.  

Despite the known pathogenicity of anti-GBM antibodies, and the correlation of disease severity with their titers, there is conflicting reports on whether anti-GBM antibody positivity correlates with disease relapse on long term follow up. The objective of this study was to assess for correlation of anti-GBM antibody positivity and disease relapse in patients with anti-GBM disease.

Methods: Patients seen in a single academic center between 1997 and 2017 were initially screened for the presence of anti-GBM disease by ICD 9/10 code for anti-GBM disease or Goodpasture’s syndrome.  435 patients were identified. Patients were then included in the study if the diagnosis was confirmed by a board certified rheumatologist or nephrologist at our institution and had positive anti-GBM antibodies or biopsy results consistent with a diagnosis of anti-GBM disease.  Relapsing disease was defined as recurrence of glomerulonephritis or pulmonary hemorrhage after the initial presentation that necessitated a change in therapy. The primary endpoint of this study was anti-GBM antibody positivity at the time of relapse.  All charts were reviewed for baseline demographics, clinical manifestations, anti-GBM antibody and ANCA positivity at the time of initial presentation; these were compared between those with relapsing and non-relapsing disease.  Results were analyzed using a two tailed standard t-test.  These same characteristics were also examined in the relapsing cohort at the time of relapse.

Results: 40 patients were confirmed as having anti-GBM disease at our institution.  Mean follow up from disease onset to the date of last follow up was 56.2 months.  8 patients had relapsing disease and 32 patients had non-relapsing disease.  Baseline characteristics and clinical manifestations were similar between groups (Table 1).  Patients with relapsing disease had a statistically higher incidence of ANCA co-positivity as compared to non-relapsing patients (62.5% vs. 21.7% respectively  p value- 0.03).

In patients with relapsing disease, only 14.7% (1/7 tested patients) had positive anti-GBM antibodies at the time of their relapse.

Conclusion: In this study, anti-GBM positivity did not correlate with disease relapse in patients with anti-GBM disease.  Patients with relapsing disease had a higher incidence of ANCA positivity, consistent with previous investigations.  In patients with newly diagnosed anti-GBM disease, ANCAs should be obtained to assess for the risk of relapse and to help guide long term follow up and treatment. Larger studies are needed to validate our results.