Catalytic Antibodies in Autoimmune Disease Mechanisms

Catalytic antibodies (abzymes) represent a class of immunoglobulins with both antigen recognition and enzymatic functions. In autoimmune diseases they emerge spontaneously or in response to chronic inflammation, contributing either to tissue damage by cleaving self-antigens or to protective antioxidant defence by neutralising reactive species. Mechanistically, these abzymes harness amino acid residues within their complementarity-determining regions to form catalytic triads analogous to conventional enzymes. They have been found to hydrolyse proteins such as myelin basic protein and myelin oligodendrocyte glycoprotein in multiple sclerosis, degrade chromatin components in systemic lupus erythematosus, and catalyse redox reactions to control oxidative stress. The dual functionality blurs the line between adaptive immunity and enzymology, offering insights into novel disease biomarkers and therapeutic strategies. Understanding the balance between pathogenic and protective catalytic antibodies may inform diagnosis, prognostic evaluation, and the design of abzyme-based interventions.

Research from Nature Portfolio

Recent studies have demonstrated a rapid methodology for converting existing monoclonal antibodies into catalytic variants via targeted deletion of residues in complementarity-determining regions. Application of this approach to influenza A virus–specific antibodies generated light chains exhibiting potent proteolytic activity against conserved haemagglutinin peptides and enhanced antigen affinity by two orders of magnitude. Structural analyses revealed reorientation of key amino acid residues to form an active catalytic site, resulting in both improved immunoreactivity and in vitro neutralisation of viral infection. This strategy promises accelerated development of abzymes for diagnostic and therapeutic applications across diverse disease contexts.

Catalytic Antibodies in Autoimmune Disease Mechanisms publication trend

The graph below shows the total number of articles in catalytic antibodies in autoimmune disease mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Catalytic antibodies (abzymes): Antibodies that combine antigen recognition with enzymatic activity, enabling substrate cleavage or modification.

Complementarity-determining region (CDR): Variable loops in an antibody’s antigen-binding domain that determine specificity and contribute to catalysis in abzymes.

Experimental autoimmune encephalomyelitis (EAE): Animal model of central nervous system inflammation used to study multiple sclerosis and related autoimmune mechanisms.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen, capable of causing cellular damage and targeted by antioxidant enzymes and abzymes.

References

1. Autoantibody–Abzymes with Catalase Activity in Experimental Autoimmune Encephalomyelitis Mice. Molecules (2023).
2. Enzymatization of mouse monoclonal antibodies to the corresponding catalytic antibodies. Scientific Reports (2024).
3. Essential Protective Role of Catalytically Active Antibodies (Abzymes) with Redox Antioxidant Functions in Animals and Humans. International Journal of Molecular Sciences (2022).
4. Immunoglobulins with Non-Canonical Functions in Inflammatory and Autoimmune Disease States. International Journal of Molecular Sciences (2020).