Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
T-Cell Subsets Dys-Regulation and Cytokines Are Predictive of RA Pathogenesis in an ACPA-Positive Background.
Cuthbert2, Richard, Parmar2, Rekha, Nam2, Jackie, Villeneuve2, Edith, Corscadden2, Diane, Henshaw2, Karen, Emery1, Paul
We reported that T-cell subset dys-regulation can predict response to treatment in early RA independently of the treatment received as well as relapse in patients who achieved clinical remission. Naïve cells frequency were the most significant circulating T-cells in early disease although, a subset of regulatory T-cell expressing CD62L showed significance. Cytokine activated T-cells (IRC) were less informative as systemic inflammation was low. The aim of the current study is to determine whether T-cell subset analysis done within 4 hours of blood collection can predict future diagnostic in early inflammatory arthritis.
60 patients with < 12 months inflammatory arthritis (IA) were enrolled; age, DAS, CRP, symptom duration, RF, ACPA and shared epitope status were included in the analysis. 6 colour flowcytometry was performed using standard protocols. 36 healthy controls were used to build the age relationship with naïve cell frequency. ELISA were used to measure cytokines and chemokines.
Of the 60 IA patients, 25 satisfied the ACR criteria for RA at baseline, the 35 remained classified as undifferentiated (UA). There was no difference at baseline between groups for age and CRP however DAS was higher in the RA group (P=0.04). There were also no difference between RA and UA for T-cell subsets with the exception of a trend for lower naïve T-cell frequency in RA (P=0.075). In relation with higher CRP, IRC frequency was also higher in RA and the relationship between CRP and IRC was confirmed using both groups (R=0.460, P=0.040). CD25highFoxP3+ Treg were reduced in both groups with no difference in CD62L+Treg. Using ACPA positivity as criteria, ACPA+ disease was associated with a trend for higher CRP (n=42, P=0.099) and lower naïve T-cell (P=0.150). In contrast naïve cell in ACPA-negative disease were close to healthy controls. IRC were only increased in ACPA+ disease with normal frequency in ACPA- patients. Similarly, both Treg and CD62L+Treg were lower and higher respectively in ACPA-positive and closer to normal in ACPA-negative disease. Serum levels of all tested cytokines differed in patients compared to healthy controls using both ACR and ACPA as criteria. IL-12 and IL-7 were reduced in both RA (P<0.001) and UA (P<0.001) and MIP-1alpha increased (P=0.02 and P=0.0001). There was no difference between ACPA-positive and negative disease for levels of MIP-1alpha and IL-7 however, IL-12 reduction was more marked in ACPA-negative disease (both P<0.001). The added value of IL7 and MIP for the diagnostic of ACPA-negative RA needs to be further anlysed.
The development of RA appears clearly associated with profoundly abnormal immunological parameters at baseline however more closely associated with ACPA-positive disease. Associated with differences in genetic background between ACPA-positive and negative diseases, these data support two divergent pathogenesis, one involving T-cell in ACPA-positive disease. Providing novel diagnostic criteria by transferring flow cytometry protocols and ELISA from research lab to routine hospital services appears promising.
To cite this abstract, please use the following information:
Cuthbert, Richard, Parmar, Rekha, Nam, Jackie, Villeneuve, Edith, Corscadden, Diane, Henshaw, Karen, et al; T-Cell Subsets Dys-Regulation and Cytokines Are Predictive of RA Pathogenesis in an ACPA-Positive Background. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1090