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AB0057 Soluble pd-1 and spd-l2 are unaffected by adalimumab treatment in early ra and associated with presence of anti-ccp and igm-rf
  1. S. R. Greisen1,
  2. K. Stengaard-Pedersen2,
  3. M. L. Hetland3,
  4. K. Hørslev-Petersen4,
  5. B. W. Deleuran5
  1. 1Immunology, AARHUS UNIVERSITETY
  2. 2Rheumatology, Aarhus University Hospital, Aarhus
  3. 3Rheumatology, Glostrup Hospital, Copenhagen
  4. 4Rheumatology, Kong Christian X’s Gigthospital, Graasten
  5. 5Immunology, Aarhus University, Aarhus, Denmark

Abstract

Background Disturbance of the balance in the immune system plays a major role in rheumatoid arthritis (RA). Programmed Death 1 (PD-1) expressed by activated T cells and its ligand (PD-L2) expressed by antigen presenting cells, are involved in negative regulation of T cell receptor induced activation 1. Both PD-1 and PD-L2 exist in soluble forms (sPD-1 and sPD-L2). Soluble PD-1 is up-regulated in RA2, but sPD-L2 has to our knowledge not been investigated.

Objectives To investigate sPD-1 and sPD-L2 in early RA patients and their association with disease.

Methods In a longitudinal set of steroid- and DMARD-naïve RA patients (n=76, <3 months’ disease) who initiated treatment with methotrexate (MTX) or MTX and adalimumab, we measured plasma levels of sPD-L2 and sPD-1 by ELISA, at baseline (0 month) and after 3 and 12 months. To remove un-specific binding, plasma samples were saturated with mouse, bovine and human IgG. We examined for correlations (Spearman’s rho) with disease parameters (DAS28, doctors VAS, HAQ, CRP), anti-CCP and IgM-RF. Data are expressed as median values (IQR).

Results Plasma levels of sPD-L2 were 3.88ng/ml (2.8-5.2) at baseline, had increased 78% after 3 months, and stayed high at 12 months (6.44ng/ml (5.5-8.1)), (both p<0.05). In contrast, plasma levels of sPD-1 showed no significant changes. Addition of adalimumab to MTX had no influence on sPD-1 or sPD-L2 plasma levels.

Baseline sPD-1 and sPD-L2 plasma levels were associated with the presence of anti-CCP antibodies (rho=0.4 and 0.3, respectively, both p<0.05) and IgM-RF (rho=0.64, p<0.0001 and rho=0.4 p<0.05). Interestingly, sPD-L2 relative to sPD-1 (sPD-L2/sPD-1) showed inverse correlation with anti-CCP and IgM-RF (all rho= -0.40, p<0.05). Changes in plasma levels of sPD-L2 (0-12 months) and sPD-1 correlated with disease parameters.

Conclusions Plasma levels of sPD-L2 and sPD-1 in RA are unaffected by addition of adalimumab to MTX treatment. The association between plasma levels of sPD-L2 and disease parameters suggests that sPD-L2 plays a vital role in disease progression. Also considering the close correlations with anti-CCP and IgM-RF, sPD-1 and sPD-L2 are possible new indicators of disease activity and progression. Because PD-1 is closely connected to the regulation of follicular T cells, our findings support the involvement of these T cells in the early phase of RA.

  1. Messal, N., Serriari, N.-E., Pastor, S., Nunès, J. A. & Olive, D. PD-L2 is expressed on activated human T cells and regulates their function. Molecular Immunology 48, 2214–2219 (2011).

  2. Wan, B. et al. Aberrant regulation of synovial T cell activation by soluble costimulatory molecules in rheumatoid arthritis. J. Immunol. 177, 8844–8850 (2006).

Disclosure of Interest None Declared

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