Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

Circulating CD4CD161 T Cells As Biomarker of Disease Activity in Recently Diagnosed, Non-Treated Rheumatoid Arthritis Patients.

Chalan,  Paulina, Abdulahad,  Wayel H., Huitema,  Minke G., Kroesen,  Bart-Jan, Brouwer,  Elisabeth, Boots,  Annemieke M.H.


Ample evidence suggests a role for T lymphocytes in the pathogenesis of rheumatoid arthritis (RA). CD161 was shown to confer tissue migratory properties to T cells and may thus contribute to tissue pathology. The role of CD161+ T cells in recently diagnosed RA has not been investigated yet. Our first objective was to provide clues on T-cell subset(s) involved in RA by analyzing frequencies of naïve (TNaive), central memory (TCM), effector memory (TEM), terminally differentiated (TTD) T lymphocytes and by assessing CD161 expression in blood of newly-diagnosed RA patients and paired peripheral blood (PB)- synovial fluid (SF) samples of late-stage RA. Secondly, we assessed the cytokine profile of PB and SF- derived CD4+CD161+ T cells. Thirdly, we investigated in a longitudinal study, the influence of regular methotrexate (MTX) treatment on circulating CD4+CD161+ T cells


Blood from recently diagnosed, non-treated RA patients (n=30), age-/sex-matched healthy controls (HC, n=27) was stained with fluorochrome-conjugated anti-CD4, CD8, CD45RO, CCR7, CD161 antibodies and analyzed using flow cytometry. 21 patients had a second measurement 3 months after start of MTX treatment. DAS28, ESR, CRP were assessed at baseline and at 3 months (after treatment). T-cell subset composition was also analyzed in paired PB and SF samples from patients with an active disease (n=9). Cytokine (TNF-a, IFN-g, IL-4, IL-17) and cytolytic granule (Perforin, Granzyme B) expression of PB- and SF- derived lymphocytes was assessed by intracellular staining and flow cytometric analysis


The frequency of CD4+ TEM was found to be significantly decreased while the frequency of CD4+ TNaive was significantly increased in newly-diagnosed RA patients when compared to HC. Of note, the frequency of CD4+CD161+ T cells, found to contain mostly effector memory cells, was significantly decreased in RA (p=0.04). The percentage and the absolute number of circulating CD4+CD161+ T cells correlated inversely with DAS28 (-0.41, p=0.028 and -0.42, p=0.023, respectively). We observed a significant enrichment of CD4+, but not CD8+ T cells expressing CD161 in SF when compared to PB (p=0.039). SF-derived CD4+CD161+ T cells showed enhanced IFN-g and reduced IL-17 expression compared to their PB- derived counterparts. After 3 months of MTX treatment, a reduction in disease severity was associated with normalization of circulating CD4+CD161+ T lymphocytes


The frequency of CD4+ TEMis significantly decreased while the frequency of CD4+ TNaive is increased in PB of early RA. The decline of circulating CD4+CD161+ T lymphocytes correlated inversely with disease activity. The observed preponderance of CD4+CD161+ T cells in SF compared to PB suggests their influx in the joint. Increased IFN-g production by SF CD4+CD161+ T cells may contribute to the disease process in RA. Furthermore, the normalisation of circulating CD4+CD161+ T cells following MTX treatment suggests that this subset might qualify as a biomarker of disease activity in RA.

To cite this abstract, please use the following information:
Chalan, Paulina, Abdulahad, Wayel H., Huitema, Minke G., Kroesen, Bart-Jan, Brouwer, Elisabeth, Boots, Annemieke M.H.; Circulating CD4CD161 T Cells As Biomarker of Disease Activity in Recently Diagnosed, Non-Treated Rheumatoid Arthritis Patients. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2342

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