Lyme Arthritis
Persistent arthritis in Borrelia burgdorferi–infected HLA–DR4–positive CD28-negative mice post–antibiotic treatment
Bettina Panagiota Iliopoulou,
Joseph Alroy,
Brigitte T. Huber,
Bettina Panagiota Iliopoulou
Tufts University School of Medicine, Boston, Massachusetts
Search for more papers by this authorJoseph Alroy
Tufts University School of Medicine, and Tufts Medical Center, Boston, Massachusetts
Search for more papers by this authorCorresponding Author
Brigitte T. Huber
Tufts University School of Medicine, Boston, Massachusetts
Department of Pathology, Tufts University School of Medicine, Jaharis 512, 150 Harrison Avenue, Boston, MA 02111Search for more papers by this authorBettina Panagiota Iliopoulou,
Joseph Alroy,
Brigitte T. Huber,
Bettina Panagiota Iliopoulou
Tufts University School of Medicine, Boston, Massachusetts
Search for more papers by this authorJoseph Alroy
Tufts University School of Medicine, and Tufts Medical Center, Boston, Massachusetts
Search for more papers by this authorCorresponding Author
Brigitte T. Huber
Tufts University School of Medicine, Boston, Massachusetts
Department of Pathology, Tufts University School of Medicine, Jaharis 512, 150 Harrison Avenue, Boston, MA 02111Search for more papers by this authorAbstract
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-γ 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.
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