BAFF blockade prevents anti-drug antibody formation in a mouse model of Pompe disease

Phillip A. Doerfler, Sushrusha Nayak, Roland W. Herzog, Laurence Morel, Barry J. Byrne

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Antibodies formed against the therapeutic protein are a life-threatening complication that arises during enzyme replacement therapy for Pompe disease (acid α-glucosidase deficiency; GAA). To provide an effective alternative to current practices, we investigated the capacity of anti-B-cell activating factor (BAFF) as a novel drug candidate to prevent antibody formation in a Pompe disease mouse model. A BAFF-neutralizing antibody was administered prophylactically and with maintenance doses in association with enzyme replacement therapy using recombinant human GAA in Gaa-/- mice. BAFF blockade delayed antibody production and increased GAA activity within tissues with protection from anaphylaxis. Anti-BAFF also resolved antibody formation during an immune response and precluded the maturation of antibody secreting cells from entering the bone marrow compartment. This treatment modality may therefore be a viable alternative for the clinical management of antibody formation for Pompe disease and has potential use against antibody formation in other protein replacement therapies.

Original languageEnglish (US)
Pages (from-to)140-147
Number of pages8
JournalClinical Immunology
Issue number2
StatePublished - Jun 1 2015
Externally publishedYes


  • Acid alpha-glucosidase
  • BAFF
  • BLyS
  • Enzyme replacement therapy
  • Pompe disease

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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