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Suppressed hetergeneous antinuclear antibody response in lymphomabearing NZB/NZW mice
Abstract:
A long-term study of cyclophophamide-induced suppression of auto-immune disease in NZB/NZW mice demonstrated the oncogenic potential of this alkylating agent. In seven of ten mice dying with lymphomas, retrospective examination of serial tests for heterogeneous ANA showed terminal decreases of titres or reversion of tests to negative. Suppressed titres were found in one of seven mice dying with other tumours and in four of twenty-nine mice succumbing to renal disease-vasculitis. Transplantation studies confirmed the association between growing lymphoma tissue and decreasing ANA titres. In the immunosuppressed host with connective tissue disease, the loss of certain auto-antibodies may signal development of a lymphoreticular neoplasm. Tumour-induced impairment of auto-immune responsiveness may reflect the loss of specific ANA that fulfil a protective role and inhibit neoplastic growth.
Insights
Cyclophosphamide treatment for autoimmune disease in mice can lead to cancer. Declining autoantibodies, like antinuclear antibodies (ANA), may signal lymphoma development in immunosuppressed animals.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Cyclophosphamide is an alkylating agent used to suppress autoimmune diseases.
- NZB/NZW mice are a model for studying autoimmune diseases like lupus.
- Autoimmune diseases are characterized by autoantibodies, such as antinuclear antibodies (ANA).
Purpose of the Study:
- To investigate the oncogenic potential of cyclophosphamide in a long-term study.
- To explore the relationship between cyclophosphamide-induced immunosuppression, autoimmune markers, and cancer development.
- To determine if changes in ANA titers correlate with lymphoma development.
Main Methods:
- Long-term administration of cyclophosphamide to NZB/NZW mice.
- Monitoring of autoimmune disease markers, including heterogeneous ANA titers.
- Retrospective analysis of tumor incidence and types.
- Transplantation studies to confirm associations between lymphoma and ANA levels.
Main Results:
- Seven out of ten mice that developed lymphomas showed decreased or negative ANA titers terminally.
- Decreased ANA titers were also observed in a smaller proportion of mice with other tumors or renal disease-vasculitis.
- Transplantation studies confirmed a link between growing lymphoma and declining ANA levels.
Conclusions:
- In cyclophosphamide-immunosuppressed mice with autoimmune disease, a loss of autoantibodies (ANA) may indicate lymphoreticular neoplasm development.
- Tumor-induced impairment of autoimmune response might involve the loss of specific ANA that could otherwise inhibit tumor growth.
- Cyclophosphamide's immunosuppressive effects may unmask or promote oncogenesis, particularly lymphomas.