TY - JOUR
T1 - A profile of immune response to herpesvirus is associated with radiographic joint damage in rheumatoid arthritis
AU - Davis, John M.
AU - Knutson, Keith L.
AU - Skinner, John A.
AU - Strausbauch, Michael A.
AU - Crowson, Cynthia S.
AU - Therneau, Terry M.
AU - Wettstein, Peter J.
AU - Matteson, Eric L.
AU - Gabriel, Sherine E.
N1 - Funding Information:
This project was supported by NIH/NCRR CTSA Grant Numbers KL2 RR024151 and UL1 RR024150. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Dr. Davis was also supported by a New Investigator Award from the Arthritis Foundation and a career development award from Mayo Foundation. The authors thank Jeaneen Alcorn for coordinating the study and Jennifer Gall and Sherry Kallies for administrative support. The authors also wish to thank Larry R. Pease, PhD, for scientific contributions and institutional support.
PY - 2012/1/31
Y1 - 2012/1/31
N2 - Introduction: Progression of joint damage despite appropriate therapy remains a significant problem for patients with rheumatoid arthritis (RA). This study was undertaken to identify profiles of immune response that correlate with radiographic joint damage as a first step toward the discovery of new pathogenic mechanisms of joint destruction in RA.Methods: The study included 58 patients with RA and 15 healthy controls. The profiles of cytokine release from peripheral blood mononuclear cells (PBMC) in response to stimulation for 48 hours with one of six stimuli, or in media alone, were measured. Immune response profiles identified for each stimulus were correlated with radiographic joint damage as defined by the Sharp-van der Heijde score (SHS), before and after multivariable adjustment. For profiles correlated with the SHS, the distributions of individual cytokines were evaluated in patients according to the severity of joint damage and compared to healthy controls.Results: The immune response profile for cytomegalovirus (CMV)/Epstein-Barr virus (EBV) stimulation was correlated with both the SHS total and erosion scores (r = 0.31, P = 0.018 and r = 0.33, P = 0.011, respectively). After adjusting for age, sex, disease duration, autoantibody status, CMV/EBV serological status, current disease activity, disability and treatments, the correlation of the CMV/EBV immune response and the SHS erosion score became stronger (r = 0.43, P < 0.003). The CMV/EBV immune response correlated with CMV IgG (r = 0.44, P < 0.001), but not with EBV IgG. The most important cytokines for the CMV/EBV immune response profile were IFN-γ, IL-2, IL-4, IL-5, IL-13 and IL-17A, all of which are associated with T-cell immunity. Both the summary immune response score and the individual responses of IFN-γ and IL-13 to CMV/EBV stimulation were associated with greater joint damage.Conclusions: A profile of immune response to purified CMV/EBV lysates is associated with radiographic joint damage. The correlation of this immune response to CMV serology implies possible involvement of latent CMV infection. Therefore, the findings suggest that the immune response to latent CMV infection could play a fundamental role in the progression of inflammation and structural joint damage in patients with RA.
AB - Introduction: Progression of joint damage despite appropriate therapy remains a significant problem for patients with rheumatoid arthritis (RA). This study was undertaken to identify profiles of immune response that correlate with radiographic joint damage as a first step toward the discovery of new pathogenic mechanisms of joint destruction in RA.Methods: The study included 58 patients with RA and 15 healthy controls. The profiles of cytokine release from peripheral blood mononuclear cells (PBMC) in response to stimulation for 48 hours with one of six stimuli, or in media alone, were measured. Immune response profiles identified for each stimulus were correlated with radiographic joint damage as defined by the Sharp-van der Heijde score (SHS), before and after multivariable adjustment. For profiles correlated with the SHS, the distributions of individual cytokines were evaluated in patients according to the severity of joint damage and compared to healthy controls.Results: The immune response profile for cytomegalovirus (CMV)/Epstein-Barr virus (EBV) stimulation was correlated with both the SHS total and erosion scores (r = 0.31, P = 0.018 and r = 0.33, P = 0.011, respectively). After adjusting for age, sex, disease duration, autoantibody status, CMV/EBV serological status, current disease activity, disability and treatments, the correlation of the CMV/EBV immune response and the SHS erosion score became stronger (r = 0.43, P < 0.003). The CMV/EBV immune response correlated with CMV IgG (r = 0.44, P < 0.001), but not with EBV IgG. The most important cytokines for the CMV/EBV immune response profile were IFN-γ, IL-2, IL-4, IL-5, IL-13 and IL-17A, all of which are associated with T-cell immunity. Both the summary immune response score and the individual responses of IFN-γ and IL-13 to CMV/EBV stimulation were associated with greater joint damage.Conclusions: A profile of immune response to purified CMV/EBV lysates is associated with radiographic joint damage. The correlation of this immune response to CMV serology implies possible involvement of latent CMV infection. Therefore, the findings suggest that the immune response to latent CMV infection could play a fundamental role in the progression of inflammation and structural joint damage in patients with RA.
KW - Cytokines
KW - Cytomegalovirus
KW - Epstein-barr virus
KW - Immune responses
KW - RA
KW - Radiographic joint damage
KW - Rheumatoid arthritis
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=84856346457&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856346457&partnerID=8YFLogxK
U2 - 10.1186/ar3706
DO - 10.1186/ar3706
M3 - Article
C2 - 22293286
AN - SCOPUS:84856346457
SN - 1478-6354
VL - 14
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - R24
ER -