PMID- 29626269
OWN - NLM
STAT- MEDLINE
DCOM- 20190110
LR  - 20190110
IS  - 1434-9949 (Electronic)
IS  - 0770-3198 (Linking)
VI  - 37
IP  - 8
DP  - 2018 Aug
TI  - Analysis of PD-1 and Tim-3 expression on CD4(+) T cells of patients with
      rheumatoid arthritis; negative association with DAS28.
PG  - 2063-2071
LID - 10.1007/s10067-018-4076-4 [doi]
AB  - Expression of T cell immunoglobulin and mucin-domain containing-3 (Tim-3) and
      programmed cell death-1 (PD-1) was studied on CD4(+) T cells of patients with
      rheumatoid arthritis (RA). Association of Tim-3 and PD-1 expression with disease 
      activity of RA patients was also addressed. A total of 37 RA patients and 31 sex-
      and age-matched healthy controls were included in this study. Disease activity of
      RA patients was determined by Disease Activity Score of 28 joints scoring system 
      (DAS28). A three-color flow cytometry method was applied to determine the
      frequency of Tim-3(+)/PD-1(+)/CD4(+) T cells. To measure the cytokine production,
      peripheral blood mononuclear cells (PBMCs) were stimulated with PMA/ionomycin.
      Concentrations of IL-17, IL-10, IFN-gamma, and TNF-alpha were measured in culture
      supernatants by ELISA. The frequency of PD-1(+)/CD4(+) and
      Tim-3(+)/PD-1(+)/CD4(+) T cells was significantly higher in patients with RA
      compared to that in controls (p = 0.0013 and p = 0.050, respectively). The
      percentage of Tim-3(+)/CD4(+) T cells was similar in patients and controls (p =
      0.4498). The RA patients have produced significant higher levels of TNF-alpha,
      IL-17, and IFN-gamma than those of healthy controls (p = 0.0121, p = 0.0417, and 
      p = 0.0478, respectively). Interestingly, an inverse correlation was found
      between the frequency of Tim-3(+)/CD4(+) cells and DAS28 of RA patients (r = -
      0.4696, p = 0.0493). Similarly, the percentage of Tim-3(+)/PD-1(+)/CD4(+) T cells
      was also revealed an inverse correlation with DAS28 (r = - 0.5268, p = 0.0493).
      Moreover, significant positive correlations were detected between the
      concentrations of TNF-alpha (r = 0.6418, p = 0.0023) and IL-17 (r = 0.4683, p =
      0.0373) with disease activity of RA patients. Our results indicate that Tim-3 and
      PD-1 are involved in immune dysregulation mechanisms of rheumatoid arthritis and 
      could be considered as useful biomarkers for determination of disease activity
      and progression.
FAU - Koohini, Zohreh
AU  - Koohini Z
AD  - Department of Immunology, School of Medicine, Mazandaran University of Medical
      Sciences, Sari, Iran.
FAU - Hossein-Nataj, Hadi
AU  - Hossein-Nataj H
AD  - Department of Immunology, School of Medicine, Mazandaran University of Medical
      Sciences, Sari, Iran.
FAU - Mobini, Maryam
AU  - Mobini M
AD  - Department of Rheumatology, Imam Khomeini Hospital, School of Medicine,
      Mazandaran University of Medical Sciences, Sari, Iran.
FAU - Hosseinian-Amiri, Aref
AU  - Hosseinian-Amiri A
AD  - Department of Rheumatology, Imam Khomeini Hospital, School of Medicine,
      Mazandaran University of Medical Sciences, Sari, Iran.
FAU - Rafiei, Alireza
AU  - Rafiei A
AD  - Department of Immunology, School of Medicine, Mazandaran University of Medical
      Sciences, Sari, Iran.
FAU - Asgarian-Omran, Hossein
AU  - Asgarian-Omran H
AUID- ORCID: http://orcid.org/0000-0003-3816-8792
AD  - Department of Immunology, School of Medicine, Mazandaran University of Medical
      Sciences, Sari, Iran. asgarianhossein@yahoo.com.
AD  - Immunogenetics Research Center, School of Medicine, Mazandaran University of
      Medical Sciences, Sari, Iran. asgarianhossein@yahoo.com.
LA  - eng
GR  - MCBRC-MAZUMS-1282/Mazandaran University of Medical Sciences
PT  - Journal Article
DEP - 20180407
PL  - Germany
TA  - Clin Rheumatol
JT  - Clinical rheumatology
JID - 8211469
RN  - 0 (HAVCR2 protein, human)
RN  - 0 (Hepatitis A Virus Cellular Receptor 2)
RN  - 0 (Interleukin-17)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Arthritis, Rheumatoid/*metabolism
MH  - CD4-Positive T-Lymphocytes/*chemistry
MH  - Case-Control Studies
MH  - Female
MH  - Flow Cytometry
MH  - Hepatitis A Virus Cellular Receptor 2/*antagonists & inhibitors
MH  - Humans
MH  - Interferon-gamma/analysis
MH  - Interleukin-17/analysis
MH  - Leukocytes, Mononuclear/chemistry
MH  - Male
MH  - Methotrexate
MH  - Middle Aged
MH  - Programmed Cell Death 1 Receptor/*analysis
MH  - Tumor Necrosis Factor-alpha/analysis
OTO - NOTNLM
OT  - Disease Activity Score
OT  - PD-1
OT  - Rheumatoid arthritis
OT  - Tim-3
EDAT- 2018/04/08 06:00
MHDA- 2019/01/11 06:00
CRDT- 2018/04/08 06:00
PHST- 2018/02/05 00:00 [received]
PHST- 2018/03/21 00:00 [accepted]
PHST- 2018/03/16 00:00 [revised]
PHST- 2018/04/08 06:00 [pubmed]
PHST- 2019/01/11 06:00 [medline]
PHST- 2018/04/08 06:00 [entrez]
AID - 10.1007/s10067-018-4076-4 [doi]
AID - 10.1007/s10067-018-4076-4 [pii]
PST - ppublish
SO  - Clin Rheumatol. 2018 Aug;37(8):2063-2071. doi: 10.1007/s10067-018-4076-4. Epub
      2018 Apr 7.