Perspectives from B cell immunology: fact and fancy

Area of Science:

• Immunology
• Genetics
• Biochemistry

Background:

• Enzyme replacement therapy (ERT) is a treatment for lysosomal storage diseases (LSDs).
• Antibody formation against therapeutic enzymes is a common challenge in ERT.
• Understanding immunogenicity and tolerance is crucial for optimizing ERT.

Purpose of the Study:

• To review antibody formation during ERT for LSDs.
• To discuss immunological concepts of immunogenicity and tolerance in ERT.
• To explore strategies for minimizing immunogenicity and potential future therapies.

Main Methods:

• Literature review of immunological concepts related to ERT in LSDs.
• Analysis of antibody formation, its impact, and adverse reactions.
• Discussion of tolerance induction and novel therapeutic strategies like gene therapy.

Main Results:

• Anti-enzyme antibodies (mainly IgG) frequently form in ERT for LSDs, except Gaucher disease, but often wane over time.
• Antibody inhibition typically does not necessitate treatment modification; hypersensitivity and infusion reactions may be antibody-mediated.
• Immune tolerance is associated with cross-reacting immunological material; gene therapy and regulatory T cells show promise in animal models.

Conclusions:

• While antibody formation is common in ERT for LSDs, it usually doesn't impede treatment significantly.
• Minimizing immunogenicity through enzyme preparation and administration is key.
• Gene therapy and immune modulation represent promising avenues for future LSD treatment.