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D-penicillamine-induced autoantibodies in a mouse model
1Unit of Pediatric Rheumatology, Rambam Medical Center, Faculty of Medicine, Haifa, Israel.
Clinical and Experimental Rheumatology
|July 1, 1995
Summary
D-penicillamine (D-PEN) induced insulin autoantibodies in mice genetically predisposed to autoimmunity. This suggests genetic background influences environmental factors in triggering autoimmune responses, potentially explaining varied autoimmune conditions in D-PEN treated patients.
Area of Science:
- Immunology
- Pharmacology
- Genetics
Background:
- Rheumatoid arthritis patients treated with D-penicillamine (D-PEN) develop insulin autoantibodies.
- Susceptibility to streptozotocin-induced immune diabetes (SIMD) varies across mouse strains (C57BL/KsJ, BALB/c, C3H/HeJ, C57BL/6).
Purpose of the Study:
- To investigate D-PEN's effect on autoantibody production in different mouse strains.
- To explore the role of genetic predisposition in D-PEN-induced immune responses.
Main Methods:
- Four mouse strains received weekly subcutaneous injections of D-PEN (1 mg or 3 mg) or PBS for 4 weeks.
- Serum autoantibodies to insulin, ssDNA, thyroglobulin, and cardiolipin were measured weekly.
Main Results:
- D-PEN induced antibodies to insulin and ssDNA in C57BL/KsJ mice (prone to SIMD).
- C3H/HeJ mice (mildly prone to SIMD) showed increased ssDNA antibodies with D-PEN.
- No significant autoantibody changes were observed in BALB/c or C57BL/6 mice, or for antibodies to thyroglobulin/cardiolipin in any strain.
Conclusions:
- D-PEN elicits an antigen-specific humoral response primarily in mice genetically susceptible to autoimmunity.
- Genetic background likely modulates the impact of environmental factors like D-PEN in initiating autoimmune responses.
- This mouse model offers insights into the diverse autoimmune manifestations observed in D-PEN-treated individuals.
