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Lyme disease in human DR4Dw4-transgenic mice
S Feng1, S W Barthold, L K Bockenstedt
1Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8031, USA.
Abstract:
The evolution of Lyme arthritis in DR4-transgenic mice infected with Borrelia burgdorferi was studied because chronic Lyme arthritis in humans is associated with an increased frequency of the HLA-DR4 allele. B10 nontransgenic and DR4-transgenic mice expressing chimeric human-mouse major histocompatibility complex class II genes in which the human alpha 1 and beta 1 domains of DR4Dw4 replaced the corresponding domains of the mouse I-E(d) were inoculated with B. burgdorferi and examined at up to 180 days for infection and disease. All mice were infected throughout the 180 days, and arthritis evolved to equal severity in transgenic and control mice within 30 days and resolved by day 120. Both groups of mice developed high antibody titers to B. burgdorferi, but antibodies to outer surface proteins A and B were not readily detectable. The DR4Dw4 transgene did not predispose mice to the development of chronic Lyme arthritis.
Insights
The HLA-DR4 gene variant did not increase Lyme arthritis severity in mice infected with Borrelia burgdorferi. This study investigated Lyme arthritis evolution in transgenic mice, finding no predisposition to chronic disease.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Chronic Lyme arthritis in humans is linked to the HLA-DR4 allele.
- Borrelia burgdorferi is the causative agent of Lyme disease.
- Understanding genetic predispositions to Lyme arthritis is crucial.
Purpose of the Study:
- To investigate the role of the HLA-DR4 allele in the pathogenesis of Lyme arthritis.
- To examine the evolution of Lyme arthritis in DR4-transgenic mice infected with Borrelia burgdorferi.
Main Methods:
- DR4-transgenic mice and non-transgenic controls were infected with Borrelia burgdorferi.
- Mice were monitored for up to 180 days to assess infection and arthritis development.
- Antibody responses to Borrelia burgdorferi were analyzed.
Main Results:
- All mice became infected and developed arthritis of similar severity, regardless of DR4 transgene presence.
- Arthritis evolved within 30 days and resolved by day 120 in both groups.
- High antibody titers to Borrelia burgdorferi were observed, but specific antibodies to outer surface proteins A and B were not readily detected.
Conclusions:
- The DR4Dw4 transgene did not confer susceptibility to chronic Lyme arthritis in this mouse model.
- The HLA-DR4 allele may not be a significant risk factor for chronic Lyme arthritis development.