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Published on: August 31, 2013
Persistent arthritis in Borrelia burgdorferi-infected HLA-DR4-positive CD28-negative mice post-antibiotic treatment
Bettina Panagiota Iliopoulou1, Joseph Alroy, Brigitte T Huber
1Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Objective:
The immunologic events that lead to persistent joint inflammation in certain patients with Lyme arthritis post-antibiotic treatment have been elusive so far. The prevalence of this condition is highest in individuals with rheumatoid arthritis-associated HLA-DR alleles. This study was undertaken to generate a murine model with persistent arthritis post-antibiotic treatment.
Methods:
We have previously shown that CD28(-/-) mice develop intermittent monarticular Lyme arthritis that is responsive to antibiotics. Since there seems to be a link in humans between persistent arthritic manifestations post-antibiotic treatment and the HLA-DR4 allele, we generated DR4+/+CD28(-/-)MHCII(-/-) mice, infected them with Borrelia burgdorferi, and subsequently treated them with antibiotics.
Results:
Thirty-eight percent of the B burgdorferi-infected DR4+/+CD28(-/-)MHCII(-/-) mice, but none of the B burgdorferi-infected CD28(-/-)MHCII(-/-) mice, remained arthritic post-antibiotic treatment. A significant fraction (36%) of these mice, but none of the mice in which arthritis resolved, had serum antibodies to outer surface protein A of B burgdorferi. After abrogation of active B burgdorferi infection, the inflammatory reaction in mice with persistent joint inflammation was restricted to the joints, since their draining lymph nodes were no longer enlarged. Increased CD20 and interferon-gamma messenger RNA expression in the inflamed joints of these mice suggested a possible role of B cells and inflammatory cytokines in the pathogenesis of persistent arthritis post-antibiotic treatment.
Conclusion:
The establishment of this murine model allows, for the first time, the elucidation of the immunologic events that lead to persistent Lyme arthritis post-antibiotic therapy in genetically susceptible individuals.
Insights
A new mouse model shows that genetic factors and Borrelia burgdorferi infection can lead to persistent Lyme arthritis after antibiotic treatment, involving B cells and inflammatory cytokines.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Persistent joint inflammation after antibiotic treatment for Lyme arthritis is poorly understood.
- Individuals with rheumatoid arthritis-associated HLA-DR alleles are disproportionately affected.
Purpose of the Study:
- To generate a murine model that mimics persistent Lyme arthritis post-antibiotic treatment.
- To investigate the immunologic basis of persistent Lyme arthritis in genetically susceptible individuals.
Main Methods:
- Generated DR4+/+CD28(-/-)MHCII(-/-) mice, infected them with Borrelia burgdorferi, and treated them with antibiotics.
- Compared arthritis development and resolution in genetically modified mice versus controls.
Main Results:
- 38% of infected DR4+/+CD28(-/-)MHCII(-/-) mice developed persistent arthritis post-antibiotic treatment.
- Persistent arthritis was associated with antibodies to outer surface protein A and localized joint inflammation.
- Increased CD20 and interferon-gamma mRNA in joints suggested roles for B cells and cytokines.
Conclusions:
- This study establishes a novel murine model for persistent Lyme arthritis.
- The model facilitates the study of immunologic events underlying persistent Lyme arthritis in susceptible individuals.
