Dataset Information

Distinct patterns of soluble leukocyte activation markers are associated with etiology and outcomes in precapillary pulmonary hypertension.

ABSTRACT: Activation of inflammatory processes has been identified as a major driver of pulmonary vascular remodeling that contributes to the development of precapillary pulmonary hypertension (PH). We hypothesized that circulating markers of leukocyte activation, reflecting monocytes/macrophages (sCD163, sCD14), T-cells (sCD25) and neutrophils (myeloperoxidase [MPO], neutrophil gelatinase-associated lipocalin [NGAL]) activity, could give prognostic information in precapillary PH. Circulating markers of leucocyte activation, sCD163, sCD14, sCD25, MPO and NGAL were measured by enzyme immunoassays in plasma from patients with idiopathic PAH (IPAH; n?=?30); patients with PAH related to associated conditions (APAH; n?=?44) and patients with chronic thromboembolic PH (CTEPH) (n?=?32), and compared with 23 healthy controls. Markers of leucocyte activation were elevated in precapillary PH with particularly high levels in APAH. The elevated levels of monocyte/macrophage marker sCD163 was independently associated with poor long-term prognosis in the group as a whole, and elevated levels of sCD25 was associated with poor prognosis in APAH, while elevated levels of sCD163 and NGAL was associated with poor prognosis in IPAH and CTEPH. Our data show leucocyte activation in precapillary PH with different profiles and impact on prognosis according to etiology. The association of sCD163 with poor outcome in fully adjusted model may be of particular interest.

SUBMITTER: Lekva T

PROVIDER: S-EPMC7596076 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Distinct patterns of soluble leukocyte activation markers are associated with etiology and outcomes in precapillary pulmonary hypertension.

Lekva Tove T Gullestad Lars L Broch Kaspar K Aukrust Pål P Andreassen Arne K AK Ueland Thor T

Scientific reports 20201029 1

Activation of inflammatory processes has been identified as a major driver of pulmonary vascular remodeling that contributes to the development of precapillary pulmonary hypertension (PH). We hypothesized that circulating markers of leukocyte activation, reflecting monocytes/macrophages (sCD163, sCD14), T-cells (sCD25) and neutrophils (myeloperoxidase [MPO], neutrophil gelatinase-associated lipocalin [NGAL]) activity, could give prognostic information in precapillary PH. Circulating markers of l ...[more]

PMID: 33122779

Similar Datasets

Project description:BackgroundAlthough pulmonary vascular bed has been the main subject of research for many years in pulmonary hypertension (PH), interest has recently started to divert towards the possibility of a co-existing peripheral microangiopathy. The aim of the current study was to investigate the presence of nailfold video-capillaroscopic (NVC) structural changes in patients with precapillary PH and to identify possible associations of NVC measurements with markers of disease severity.Methods? prospective case-control study was performed in 28 consecutive patients with precapillary PH [14 with idiopathic pulmonary arterial hypertension (IPAH) and 14 with chronic thromboembolic pulmonary hypertension (CTEPH)] and 30 healthy controls. NVC quantitative and qualitative parameters were evaluated using Optilia Digital Capillaroscope. To ensure inter-observer repeatability capillaroscopic images were reviewed by two independent investigators. For multiple comparisons among continuous variables, one-way ANOVA or the Kruskal-Wallis test were used. Differences between the groups were tested with post-hoc analysis with adjustment for multiple comparisons (Bonferroni test).ResultsBoth IPAH (71.4% were women, mean age 53.1?±?13.4 years) and CTEPH (64.3% women, mean age 60.9?±?14.4 years) groups presented reduced capillary density compared to healthy controls (8.4?±?1.2 loops/mm and 8.0?±?1.2 loops/mm vs. 9.7?±?0.81 loops/mm, p?<?0.001) and increased loop width (15.7?±?3.9 ?m and 15.8?±?1.9 ?m vs. 11.5?±?2.3 ?m, p?<?0.001). More than half of patients with IPAH presented microhaemorrhages on capillary nailfold, while increased shape abnormalities in capillary morphology and more capillary thrombi per linear mm were detected in patients with CTEPH compared to patients with IPAH and healthy controls. All PH patients presented a non-specific NVC pattern compared to controls (p?<?0.001).ConclusionThe findings of the study reveal a degree of significant peripheral microvascular alterations in patients with IPAH and CTEPH, suggesting a generalized impairment of peripheral microvasculature in pulmonary vascular disease.

Project description:IntroductionSoluble markers of B cell activation are interesting diagnostic and prognostic tools in autoimmune diseases. Data in systemic sclerosis (SSc) are scarce and few studies focused on their association with disease characteristics.Methods1. Serum levels of 14 B cell biomarkers (β2-microglobulin, rheumatoid factor (RF), immunoglobulins (Ig) G, IgA, IgM, BAFF, APRIL, soluble (s)TACI, sBCMA sCD21, sCD23, sCD25, sCD27, CXCL13) were measured in SSc patients and healthy controls (HC). 2. Associations between these biomarkers and SSc characteristics were assessed. 3. The pathophysiological relevance of identified associations was explored by studying protein production in B cell culture supernatant.ResultsIn a discovery panel of 80 SSc patients encompassing the broad spectrum of disease manifestations, we observed a higher frequency of RF positivity, and increased levels of β2-microglobulin, IgG and CXCL13 compared with HC. We found significant associations between several biomarkers and SSc characteristics related to disease phenotype, activity and severity. Especially, serum IgG levels were associated with pulmonary hypertension (PH); β2-microglobulin with Nt-pro-BNP and DLCO; and BAFF with peak tricuspid regurgitation velocity (TRV). In a validation cohort of limited cutaneous SSc patients without extensive ILD, we observed lower serum IgG levels, and higher β2-microglobulin, sBCMA, sCD23 and sCD27 levels in patients with pulmonary arterial hypertension (PAH). BAFF levels strongly correlated with Nt-pro-BNP levels, FVC/DLCO ratio and peak TRV in SSc-PAH patients. Cultured SSc B cells showed increased production of various angiogenic factors (angiogenin, angiopoietin-1, VEGFR-1, PDGF-AA, MMP-8, TIMP-1, L-selectin) and decreased production of angiopoietin-2 compared to HC.ConclusionSoluble markers of B cell activation could be relevant tools to assess organ involvements, activity and severity in SSc. Their associations with PAH could plead for a role of B cell activation in the pathogenesis of pulmonary microangiopathy. B cells may contribute to SSc vasculopathy through production of angiogenic mediators.

Dataset Information

Distinct patterns of soluble leukocyte activation markers are associated with etiology and outcomes in precapillary pulmonary hypertension.

Publications

Distinct patterns of soluble leukocyte activation markers are associated with etiology and outcomes in precapillary pulmonary hypertension.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets