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.
Dys-Regulation of T-Cell Subsets and Cytokines Is Associated with the Development of Inflammatory Symptoms in ACPA-Positive Asymptomatic Individual.
Cuthbert2, Richard J., Parmar2, Rekha, Nam2, Jackie, Villeneuve2, Edith, Corscadden2, Diane, Henshaw2, Karen, Emery1, Paul
We reported that T-cell subset dys-regulation can predict evolution towards rheumatoid arthritis (RA) from early symptoms, response to treatment in early disease as well as relapse in patients who achieved clinical remission. Naïve cells were the most informative circulating T-cells subset in early disease. Cytokine activated T-cells (IRC) were less informative as systemic inflammation is low in early disease. Asymptomatic ACPA-positive individual are at high risk of developing RA. The aim of the current study is to determine whether T-cell subset and cytokine analysis can predict future development of inflammatory symptoms in this group.
35 asymptomatic ACPA+ individuals were enrolled; they were recruited if they had new onset musculoskeletal pain but no synovitis on clinical examination. 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.
35 individuals were recruited and followed for 12 months. There was clear difference at baseline between ACPA+ individuals and controls for naïve (P<0.0001), CD25highFoxp3+ Treg (P=0.020) and CD62L+Treg (P=0.001). IRC were not increased in asymptomatic individuals. During follow-up, 6 individuals were diagnosed with undifferentiated arthritis (UA), 6 with RA, 9 with non-inflammatory osteoarthritis or connective tissue disease and 16 remained with non-specific musculoskeletal symptoms or arthralgia. Analysis based on follow-up showed reduced naïve T-cell (P=0.007) and Treg (P=0.090) in arthralgia and CD62L+Treg frequency were increased (P<0.0001). In the group developing IA, naïve cells were reduced (P<0.0001) but Treg were not different from controls. CD62L+Treg in contrast were significantly reduced (P=0.025). All OA/CTD individuals were close to controls. Furthermore, OA/CTD patients compared to the age-naïve frequency relationship in controls were above normal, the arthralgia group was close to controls and IA patients below. Serum levels of IL-12 and IL-7 cytokines differed in arthralgia individuals compared to controls (P<0.0001) but MIP-1alpha levels were not raised. On follow-up reduced IL-12 (P=0.007) and IL-7 (P=0.019) were observed in the arthralgia group. In the group developing IA, IL-12 (P<0.0001) and IL-7 (P=0.006) were even more reduced and MIP-1alpha raised (P=0.018). In OA/CTD individuals, only IL-12 levels were reduced (P<0.001).
In ACPA+ asymptomatic individuals, the future development of inflammatory symptom appears clearly associated with abnormal immunological parameters at baseline. Furthermore, data suggest that Treg's involvement may be in the true pre-clinical phase and this battle is lost by the time symptoms develop. More work is needed to determine if loss of naïve cells is a cause or a consequence of this dys-regulation on T-cells, however, loss of CD62L+Treg suggests a role for the thymus.
To cite this abstract, please use the following information:
Cuthbert, Richard J., Parmar, Rekha, Nam, Jackie, Villeneuve, Edith, Corscadden, Diane, Henshaw, Karen, et al; Dys-Regulation of T-Cell Subsets and Cytokines Is Associated with the Development of Inflammatory Symptoms in ACPA-Positive Asymptomatic Individual. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1254