Document Detail


Dysregulation of CD4+CD25(high) T cells in the synovial fluid of patients with antibiotic-refractory Lyme arthritis.
MedLine Citation:
PMID:  23450683     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To examine the role of immune dysregulation in antibiotic-refractory Lyme arthritis by comparing the phenotype, frequency, and function of CD4+ Teff cells and Treg cells in patients with antibiotic- responsive arthritis and patients with antibiotic-refractory arthritis.
METHODS: Matched peripheral blood and synovial fluid samples from 15 patients with antibiotic-responsive arthritis were compared with those from 16 patients with antibiotic-refractory arthritis, using flow cytometry, suppression assays, and cytokine assays.
RESULTS: Critical differences between the 2 patient groups were observed in the synovial fluid CD4+CD25(high) population, a cell subset usually composed of FoxP3-positive Treg cells. In patients with antibiotic-refractory arthritis, this cell population often had fewer FoxP3-positive cells and a greater frequency of FoxP3-negative (Teff) cells compared with patients with antibiotic-responsive arthritis. Moreover, the expression of glucocorticoid-induced tumor necrosis factor receptor and OX40 on CD4+CD25(high) cells was significantly higher in the antibody-refractory group. Suppression assays showed that CD4+CD25(high) cells in patients with antibiotic-refractory arthritis did not effectively suppress proliferation of CD4+CD25- cells or secretion of interferon-γ and tumor necrosis factor α, whereas those cells in patients with antibiotic-responsive arthritis did suppress proliferation of CD4+CD25- cells and secretion of interferon-γ and tumor necrosis factor α. Finally, in the antibiotic-refractory group, higher ratios of CD25(high) FoxP3-negative cells to CD25(high) FoxP3-positive cells correlated directly with a longer duration of arthritis after antibiotic treatment.
CONCLUSION: Patients with antibiotic-refractory Lyme arthritis often have lower frequencies of Treg cells, higher expression of activation coreceptors, and less effective inhibition of proinflammatory cytokines. This suggests that immune responses in these patients are excessively amplified, leading to immune dysregulation and antibiotic-refractory arthritis.
Authors:
Nalini K Vudattu; Klemen Strle; Allen C Steere; Elise E Drouin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-03     Completed Date:  2013-08-13     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1643-53     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
CD4-Positive T-Lymphocytes / immunology*
Child
Cytokines / analysis*
Drug Resistance, Microbial
Female
Flow Cytometry
Humans
Interleukin-2 Receptor alpha Subunit
Lyme Disease / immunology*
Male
Middle Aged
Phenotype
Synovial Fluid / immunology*
T-Lymphocytes, Regulatory / immunology*
Young Adult
Grant Support
ID/Acronym/Agency:
AI-101175/AI/NIAID NIH HHS; AR-20358/AR/NIAMS NIH HHS; R01 AI101175/AI/NIAID NIH HHS; R01 AR020358/AR/NIAMS NIH HHS; R56 AI101175/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Interleukin-2 Receptor alpha Subunit
Comments/Corrections

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