MicroRNA Expression Shows Inflammatory Dysregulation and Tumor-Like Proliferative Responses in Joints of Patients With Postinfectious Lyme Arthritis. Arthritis Rheumatol 2017 May;69(5):1100-1110
Date
01/12/2017Pubmed ID
28076897Pubmed Central ID
PMC5406251DOI
10.1002/art.40039Scopus ID
2-s2.0-85018719753 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
OBJECTIVE: Lyme arthritis (LA) is caused by infection with Borrelia burgdorferi and usually resolves following spirochetal killing with antibiotics. However, in some patients, arthritis persists after antibiotic therapy. To provide insights into underlying pathogenic processes associated with antibiotic-refractory LA (postinfectious LA), we analyzed differences in microRNA (miRNA) expression between LA patients with active infection and those with postinfectious LA.
METHODS: MicroRNA expression was assayed in synovial fluid (SF) from LA patients before and after oral and intravenous antibiotic therapy, and in synovial tissue obtained months after antibiotic therapy from patients with postinfectious LA. SF and tissue from patients with other forms of arthritis, such as rheumatoid arthritis (RA) and osteoarthritis, were used for comparison.
RESULTS: SF from LA patients during active infection had marked elevations of white blood cells, particularly polymorphonuclear leukocytes, accompanied by elevated levels of microRNA-223 (miR-223). In contrast, SF from postantibiotic LA patients contained greater percentages of lymphocytes and mononuclear cells. SF from postantibiotic LA patients also exhibited marked inflammatory (miR-146a, miR-155), wound repair (miR-142), and proliferative (miR-17-92) miRNA signatures, and higher levels of these miRNAs correlated with longer arthritis duration. Levels of miR-146a, miR-155, miR-142, miR-223, and miR-17-92 were also elevated in synovial tissue in late postinfectious LA, and levels of let-7a were reduced, similar to RA.
CONCLUSION: During active infection, miRNA expression in SF reflected an immune response associated with bacterial killing, while in postinfectious LA, miRNA expression in SF and synovial tissue reflected chronic inflammation, synovial proliferation, and breakdown of wound repair processes, showing that the nature of the arthritis was altered after spirochetal killing.
Author List
Lochhead RB, Strle K, Kim ND, Kohler MJ, Arvikar SL, Aversa JM, Steere ACAuthor
Robert Lochhead PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Aged
Anti-Bacterial Agents
Arthritis, Reactive
Child
Female
Gene Expression Regulation
Humans
Inflammation
Lyme Disease
Male
MicroRNAs
Middle Aged
Synovial Fluid
Synovial Membrane
Young Adult
