PMID- 36555549
OWN - NLM
STAT- MEDLINE
DCOM- 20221226
LR  - 20230308
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 24
DP  - 2022 Dec 14
TI  - CTLA-4 Expression Is a Promising Biomarker of Idiopathic Pulmonary Arterial 
      Hypertension and Allows Differentiation of the Type of Pulmonary Hypertension.
LID - 10.3390/ijms232415910 [doi]
LID - 15910
AB  - Pulmonary arterial hypertension (PAH) is an increasingly frequently diagnosed 
      disease, the molecular mechanisms of which have not been thoroughly investigated. 
      The aim of our study was to investigate subpopulations of lymphocytes to better 
      understand their role in the molecular pathomechanisms of various types of PAH 
      and to find a suitable biomarker that could be useful in the differential 
      diagnosis of PAH. Using flow cytometry, we measured the frequencies of lymphocyte 
      subpopulations CD4+CTLA-4+, CD8+ CTLA-4+ and CD19+ CTLA-4+ in patients with 
      different types of PAH, namely pulmonary arterial hypertension associated with 
      congenital heart disease (CHD-PAH), pulmonary arterial hypertension associated 
      with connective tissue disorders (CTD-PAH), chronic thromboembolic pulmonary 
      hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH), and 
      in an age- and sex-matched control group in relation to selected clinical 
      parameters. Patients in the iPAH group had the significantly highest percentage 
      of CD4+CTLA-4+ T lymphocytes among all PAH groups, as compared to those in the 
      control group (p < 0.001), patients with CTEPH (p < 0.001), CTD-PAH (p < 0.001) 
      and CHD-PAH (p < 0.01). In iPAH patients, the percentages of CD4+CTLA-4+ T cells 
      correlated strongly positively with the severity of heart failure New York Heart 
      Association (NYHA) Functional Classification (r = 0.7077, p < 0.001). Moreover, 
      the percentage of B CD19+CTLA-4+ cells strongly positively correlated with the 
      concentration of NT-proBNP (r = 0.8498, p < 0.001). We have shown that 
      statistically significantly higher percentages of CD4+CTLA-4+ (p </= 0.01) and CD8+ 
      CTLA-4+ (p </= 0.001) T cells, measured at the time of iPAH diagnosis, were found 
      in patients who died within 5 years of the diagnosis, which allows us to consider 
      both of the above lymphocyte subpopulations as a negative prognostic/predictive 
      factor in iPAH. CTLA-4 may be a promising biomarker of noninvasive detection of 
      iPAH, but its role in planning the treatment strategy of PAH remains unclear. 
      Further studies on T and B lymphocyte subsets are needed in different types of 
      PAH to ascertain the relationships that exist between them and the disease.
FAU - Tomaszewski, Michal
AU  - Tomaszewski M
AUID- ORCID: 0000-0001-6993-2154
AD  - Department of Cardiology, Medical University of Lublin, 20-954 Lublin, Poland.
FAU - Malkowska, Paulina
AU  - Malkowska P
AUID- ORCID: 0000-0003-2430-5020
AD  - Doctoral School, University of Szczecin, 71-412 Szczecin, Poland.
AD  - Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland.
FAU - Sierawska, Olga
AU  - Sierawska O
AUID- ORCID: 0000-0003-3567-7786
AD  - Doctoral School, University of Szczecin, 71-412 Szczecin, Poland.
AD  - Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland.
FAU - Hrynkiewicz, Rafal
AU  - Hrynkiewicz R
AUID- ORCID: 0000-0002-0688-6928
AD  - Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland.
FAU - Mroczek, Ewa
AU  - Mroczek E
AD  - Department of Cardiology, Institute of Heart Diseases, Jan Mikulicz-Radecki 
      University Teaching Hospital, 51-124 Wroclaw, Poland.
FAU - Darocha, Szymon
AU  - Darocha S
AUID- ORCID: 0000-0001-8298-9243
AD  - Department of Pulmonary Hypertension, Thromboembolic Diseases and Cardiology, 
      Centre of Postgraduate Medical Education, 05-400 Otwock, Poland.
FAU - Hymos, Anna
AU  - Hymos A
AD  - Department of Experimental Immunology, Medical University of Lublin, 20-093 
      Lublin, Poland.
FAU - Blaszczak, Piotr
AU  - Blaszczak P
AD  - Department of Cardiology, Cardinal Wyszynski Hospital, 20-718 Lublin, Poland.
FAU - Grywalska, Ewelina
AU  - Grywalska E
AUID- ORCID: 0000-0002-0451-4741
AD  - Department of Experimental Immunology, Medical University of Lublin, 20-093 
      Lublin, Poland.
FAU - Niedzwiedzka-Rystwej, Paulina
AU  - Niedzwiedzka-Rystwej P
AUID- ORCID: 0000-0003-4065-3842
AD  - Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland.
LA  - eng
GR  - DS640 and DS376/Medical University of Lublin/
PT  - Journal Article
DEP - 20221214
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Biomarkers)
SB  - IM
MH  - Humans
MH  - *Hypertension, Pulmonary
MH  - Familial Primary Pulmonary Hypertension/metabolism
MH  - *Pulmonary Arterial Hypertension/complications
MH  - CTLA-4 Antigen
MH  - Biomarkers
MH  - Cell Differentiation
PMC - PMC9783197
OTO - NOTNLM
OT  - CTLA-4
OT  - lymphocytes
OT  - pulmonary arterial hypertension
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/24 06:00
MHDA- 2022/12/27 06:00
PMCR- 2022/12/14
CRDT- 2022/12/23 01:34
PHST- 2022/10/08 00:00 [received]
PHST- 2022/12/06 00:00 [revised]
PHST- 2022/12/07 00:00 [accepted]
PHST- 2022/12/23 01:34 [entrez]
PHST- 2022/12/24 06:00 [pubmed]
PHST- 2022/12/27 06:00 [medline]
PHST- 2022/12/14 00:00 [pmc-release]
AID - ijms232415910 [pii]
AID - ijms-23-15910 [pii]
AID - 10.3390/ijms232415910 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Dec 14;23(24):15910. doi: 10.3390/ijms232415910.