PMID- 24182347
OWN - NLM
STAT- MEDLINE
DCOM- 20140527
LR  - 20181202
IS  - 1502-7732 (Electronic)
IS  - 0300-9742 (Linking)
VI  - 43
IP  - 2
DP  - 2014
TI  - Increased soluble programmed death-1 (sPD-1) is associated with disease activity 
      and radiographic progression in early rheumatoid arthritis.
PG  - 101-8
LID - 10.3109/03009742.2013.823517 [doi]
AB  - OBJECTIVES: Programmed death-1 (PD-1) is an immunoregulatory molecule functioning 
      by down-regulating immune responses. PD-1 is present on follicular helper T cells 
      (TFH) and is important in the formation of plasma cells. PD-1 exists in a 
      bioactive soluble form (sPD-1) and is thought to be implicated in disease 
      activity in chronic rheumatoid arthritis (RA). METHOD: We measured sPD-1 at 
      baseline and 9 months after treatment initiation in plasma from early RA patients 
      (n = 34). We tested for correlations with the Disease Activity Score using 28 
      joint counts (DAS28), the Health Assessment Questionnaire (HAQ) score, 
      immunoglobulin M rheumatoid factor (IgM-RF), anti-cyclic citrullinated peptide 
      (anti-CCP) antibodies, C-reactive protein (CRP), interleukin-21 (IL-21), and 
      total Sharp score (TSS). We also measured sPD-1 in plasma from healthy volunteers 
      (HV) (n = 20) and in plasma and synovial fluid (SF) from patients with chronic RA 
      (> 8 years of disease, n = 30). We further investigated the cellular expression 
      of PD-1 and its ligand PD-L1. RESULTS: sPD-1 concentrations in early [median 
      0.421 ng/mL, interquartile range (IQR) 0.04-2.560 ng/mL] and chronic (median 
      0.239 ng/mL, IQR 0.184-0.584 ng/mL) RA were increased compared with HV (median 
      0.04 ng/mL, IQR 0.04-0.04 ng/mL) (all p < 0.005). In early RA the change in sPD-1 
      was associated with DAS28 (r = 0.363, p < 0.05) and HAQ score (r = 0.554, p < 
      0.05) and inversely with TSS at 3-5 years (r = -0.468, p < 0.05). sPD-1 
      concentration correlated with IgM-RF, anti-CCP antibodies, and IL-21 (all p < 
      0.05). PD-1 was primarily expressed by synovial memory T cells whereas PD-L1 was 
      mainly expressed by synovial monocytes. CONCLUSIONS: The significantly elevated 
      plasma levels of sPD-1 in early RA, the association with core disease parameters, 
      and the inverse correlation with TSS suggest that sPD-1 is an important mediator 
      in inflammatory and radiographic disease progression.
FAU - Greisen, S R
AU  - Greisen SR
AD  - Institute of Biomedicine, University of Aarhus , Aarhus , Denmark.
FAU - Rasmussen, T K
AU  - Rasmussen TK
FAU - Stengaard-Pedersen, K
AU  - Stengaard-Pedersen K
FAU - Hetland, M L
AU  - Hetland ML
FAU - Horslev-Petersen, K
AU  - Horslev-Petersen K
FAU - Hvid, M
AU  - Hvid M
FAU - Deleuran, B
AU  - Deleuran B
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20131101
PL  - England
TA  - Scand J Rheumatol
JT  - Scandinavian journal of rheumatology
JID - 0321213
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Biomarkers)
RN  - 0 (Interleukins)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (cyclic citrullinated peptide)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 9009-79-4 (Rheumatoid Factor)
RN  - 9842X06Q6M (Betamethasone)
RN  - MKM3CA6LT1 (interleukin-21)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Aged
MH  - Antibodies, Anti-Idiotypic/blood
MH  - Arthritis, Rheumatoid/*blood/*diagnostic imaging/drug therapy
MH  - Betamethasone/therapeutic use
MH  - Biomarkers/blood
MH  - Case-Control Studies
MH  - Cyclosporine/therapeutic use
MH  - *Disease Progression
MH  - Drug Therapy, Combination
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Interleukins/blood
MH  - Longitudinal Studies
MH  - Male
MH  - Methotrexate/therapeutic use
MH  - Middle Aged
MH  - Peptides, Cyclic/immunology
MH  - Programmed Cell Death 1 Receptor/*blood
MH  - Radiography
MH  - Rheumatoid Factor/blood
MH  - *Severity of Illness Index
EDAT- 2013/11/05 06:00
MHDA- 2014/05/28 06:00
CRDT- 2013/11/05 06:00
PHST- 2013/11/05 06:00 [entrez]
PHST- 2013/11/05 06:00 [pubmed]
PHST- 2014/05/28 06:00 [medline]
AID - 10.3109/03009742.2013.823517 [doi]
PST - ppublish
SO  - Scand J Rheumatol. 2014;43(2):101-8. doi: 10.3109/03009742.2013.823517. Epub 2013 
      Nov 1.