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.


STAT3 Phosphorylation of Circulating Leukocytes Correlates with Disease Activity in Early Untreated Rheumatoid Arthritis.

Kuuliala1,  Krista, Kuuliala1,  Antti, Aittomaki1,  Saara, Oksanen1,  Suvi, Siitonen2,  Sanna, Kautiainen3,  Hannu, Leirisalo-Repo2,  Marjatta

Haartman Institute, Helsinki, Finland
Helsinki University Central Hospital, Helsinki, Finland
Central Finland Central Hospital, Jyväskylä, Finland

Background/Purpose:

Signal transducer and activator of transcription (STAT) 3 is an important transcription factor in the regulation of inflammation. Experimental models suggest a role for STAT3 in the pathogenesis of RA [1, 2]. We aimed to evaluate STAT3 activation in peripheral blood leukocytes in early untreated RA in relation to disease activity.

Methods:

Blood samples were obtained from 31 patients diagnosed with early RA who had not received prior DMARDs or corticosteroids. The mean age of the patients was 47 years (SD 14), median duration of symptoms 8 months (interquartile range 3–24 months), 81% were women, 81% rheumatoid factor positive, and 84% anti-CCP positive. Disease activity was evaluated by calculating the DAS28 score (available in 29 patients). The levels of activated STAT3 in leukocyte subsets (CD14+, CD3+CD4+, CD3+CD8+, CD19+) were determined by flow cytometry following lysis of erythrocytes, fixation and permeabilization of leukocytes, and incubation with phospho-specific (pY705) anti-STAT3 monoclonal antibody (as described in [3]). The proportion of pSTAT3 positive cells was determined using an electronic gate set to include <5% of positively fluorescing cells from a healthy control subject. Correlation coefficients were calculated by Spearman method.

Results:

The proportion of pSTAT3 positive CD4+ cells was increased compared to controls in 18/31 patients (58%), CD8+ in 12/31 (39%), CD19+ in 8/31 (26%), and CD14+ in 17/31 (55%). DAS28 correlated with the proportion of pSTAT3+ CD4+ cells (Table), as well as the ratio of CD4+/CD14+ cells and CD4+/CD19+ cells (Table, Figure).

Table Correlation of DAS28 with the proportion of pSTAT3 positive leukocyte subsets.

Cellsrp
CD3+CD4+0.370.047
CD14+-0.060.74
CD19+-0.300.11
CD3+CD4+ toCD14+0.410.028
CD+CD4+to CD19+0.440.017
CD14+ to CD19+0.080.69

Figure. Correlation of DAS28 with the proportion of pSTAT3+ CD3+CD4+ to pSTAT3+ CD14+ cells. Filled in symbols denote anti-CCP positive and blank symbols denote anti-CCP negative patients.

Conclusion:

STAT3 is constitutively activated in circulating leukocytes in early RA. The proportion of pSTAT3+ CD4+ cells correlates with disease activity evaluated by DAS28. Circulating lymphocyte STAT3 activation is not a unique feature of RA since it has also been reported in primary Sjögren's syndrome [4] as well as in acute pancreatitis with severe systemic inflammation [3]. Our results emphasize the heterogeneous involvement of immune inflammatory cells and may provide a novel strategy for personalized medicine in the treatment of early RA.

References:

1.Krause,  et al. J Immunol 2002;169:6610-6.

2.de Hooge,  et al. Arthritis Rheum 2004;50:2014-23.

3.Oiva,  et al. Crit Care 2010;14:R207.

4.Ramos,  et al. Scand J Rheumatol 2008;37:35-9.

To cite this abstract, please use the following information:
Kuuliala, Krista, Kuuliala, Antti, Aittomaki, Saara, Oksanen, Suvi, Siitonen, Sanna, Kautiainen, Hannu, et al; STAT3 Phosphorylation of Circulating Leukocytes Correlates with Disease Activity in Early Untreated Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2570
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