title: Persistent arthritis in Borrelia burgdorferi-infected HLA-DR4-positive CD28-negative mice post-antibiotic treatment.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
authors.forename: Bettina Panagiota
authors.initials: BP
authors.lastname: Iliopoulou
authors.forename: Joseph
authors.initials: J
authors.lastname: Alroy
authors.forename: Brigitte T
authors.initials: BT
authors.lastname: Huber
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000907:Antibodies, Bacterial / Q000097:blood; D018951:Antigens, CD20 / Q000235:genetics; D000954:Antigens, Surface / Q000276:immunology; D001170:Arthritis, Infectious / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology; D025065:Borrelia burgdorferi; D018106:CD28 Antigens / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D008074:Lipoproteins / Q000276:immunology; D008193:Lyme Disease / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D016036:Seroepidemiologic Studies
chemical_list: D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D018951:Antigens, CD20; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D018106:CD28 Antigens; D015804:HLA-DR4 Antigen; D008074:Lipoproteins; C072045:OspA protein; D012333:RNA, Messenger; D007371:Interferon-gamma