Dataset Information

Using imlifidase to elucidate the characteristics and importance of anti-GBM antibodies produced after start of treatment.

ABSTRACT:

Background

Autoantibodies are common in glomerulonephritis, but the clinical benefit of rapid elimination has not been determined, even in anti-glomerular basement membrane (GBM) disease. Even less is known about the importance of autoantibody characteristics, including epitope specificity and immunoglobulin G (IgG) subclass distribution. We aimed to address this by characterizing the autoantibody profile in anti-GBM patients: we utilized samples from the GOOD-IDES-01 (treating GOODpasture's disease with Imunoglobulin G Degrading Enzyme of Streptococcus pyogenous) (ClinicalTrials.gov identifier: NCT03157037) trial , where imlifidase, which cleaves all IgG in vivo within hours, was given to 15 anti-GBM patients.

Methods

In the GOOD-IDES-01 trial, plasmapheresis was (re)started if anti-GBM antibodies rebounded. Serum samples were collected prospectively for 6 months and analyzed for anti-GBM epitope specificity using recombinant constructs of the EA and EB epitopes, IgG subclass using monoclonal antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA). The results were correlated with clinical data.

Results

Patients with a rebound (n = 10) tended to have lower eGFR at 6 months (11 vs 34 mL/min/1.73 m2, P = .055), and patients with dialysis at 6 months had a higher EB/EA ratio at rebound (0.8 vs 0.5, P = .047). Moreover, two patients demonstrated increasing epitope restriction and several patients displayed a shift in subclass distribution at rebound. Six patients were double positive for ANCA. ANCA rebound was seen in 50% of patients; only one patient remained ANCA positive at 6 months.

Conclusions

In this study, rebound of anti-GBM antibodies, especially if directed against the EB epitope, was associated with a worse outcome. This supports the notion that all means should be used to eliminate anti-GBM antibodies. In this study ANCA was removed early and long-term by imlifidase and cyclophosphamide.

SUBMITTER: Tyrberg L

PROVIDER: S-EPMC10730795 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Using imlifidase to elucidate the characteristics and importance of anti-GBM antibodies produced after start of treatment.

Tyrberg Linnéa L Andersson Fanny F Uhlin Fredrik F Hellmark Thomas T Segelmark Mårten M

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20231201 1

<h4>Background</h4>Autoantibodies are common in glomerulonephritis, but the clinical benefit of rapid elimination has not been determined, even in anti-glomerular basement membrane (GBM) disease. Even less is known about the importance of autoantibody characteristics, including epitope specificity and immunoglobulin G (IgG) subclass distribution. We aimed to address this by characterizing the autoantibody profile in anti-GBM patients: we utilized samples from the GOOD-IDES-01 (treating GOODpastu ...[more]

PMID: 37385828

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Dataset Information

Using imlifidase to elucidate the characteristics and importance of anti-GBM antibodies produced after start of treatment.

Background

Methods

Results

Conclusions

Publications

Using imlifidase to elucidate the characteristics and importance of anti-GBM antibodies produced after start of treatment.

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