Recent work in preclinical models suggests that signalling via the pro-angiogenic and proinflammatory

cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary

hypertension (PH). The objective of this study was to establish whether circulating concentrations

of CXCL12α were elevated in patients with PAH and related to mortalit

Allan Lawrie

Allison Morton

B Raychaudhuri

Brian N. McCullagh

Caroline O’Connell

CC Bleul

Charles Elliot

Christine M. Costello

CJ Rhodes

CM Costello

D Montani

David G. Kiely

DB Badesch

DG Kiely

E Sartina

G Simonneau

GE D'Alonzo

H Katsushi

JM Burns

Joseph Najbauer

K Balabanian

K Satoh

K Stellos

KC Young

KP Kuhn

L Yu

LA Madge

Lili Li

M Humbert

M Rabinovitch

M Toshner

Mary Codd

N Gambaryan

N Hopkins

O Sitbon

Paul McLoughlin

RL Benza

Robin Condliffe

S Farha

Sean Gaine

VV McLaughlin

PubMed

Recent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12α were elevated in patients with PAH and related to mortality.Plasma samples were collected from patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with connective tissue diseases (CTD-PAH) attending two pulmonary hypertension referral centres (n = 95) and from age and gender matched healthy controls (n = 44). Patients were subsequently monitored throughout a period of five years.CXCL12α concentrations were elevated in PAH groups compared to controls (P<0.05) and receiver-operating-characteristic analysis showed that plasma CXCL12α concentrations discriminated patients from healthy controls (AUC 0.80, 95% confidence interval 0.73-0.88). Kaplan Meier analysis indicated that elevated plasma CXCL12α concentration was associated with reduced survival (P<0.01). Multivariate Cox proportional hazards model showed that elevated CXCL12α independently predicted (P<0.05) earlier death in PAH with a hazard ratio (95% confidence interval) of 2.25 (1.01-5.00). In the largest subset by WHO functional class (Class 3, 65% of patients) elevated CXCL12α independently predicted (P<0.05) earlier death, hazard ratio 2.27 (1.05-4.89).Our data show that elevated concentrations of circulating CXCL12α in PAH predicted poorer survival. Furthermore, elevated circulating CXCL12α was an independent risk factor for death that could potentially be included in a prognostic model and guide therapy

McCullagh Brian N.

Costello Christine M.

Li Lili

O’Connell Caroline

Codd Mary

Lawrie Allan

Morton Allison

Kiely David G.

Condliffe Robin

Elliot Charles

McLoughlin Paul

Gaine Sean

Public Library of Science (PLOS)

Elevated Plasma CXCL12α Is Associated with a Poorer Prognosis in Pulmonary Arterial Hypertension

Recent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12a were elevated in patients with PAH and related to mortality. Plasma samples were collected from patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with connective tissue diseases (CTD-PAH) attending two pulmonary hypertension referral centres (n = 95) and from age and gender matched healthy controls (n = 44). Patients were subsequently monitored throughout a period of five years. CXCL12a concentrations were elevated in PAH groups compared to controls (P&lt;0.05) and receiver-operating-characteristic analysis showed that plasma CXCL12a concentrations discriminated patients from healthy controls (AUC 0.80, 95% confidence interval 0.73-0.88). Kaplan Meier analysis indicated that elevated plasma CXCL12a concentration was associated with reduced survival (P&lt;0.01). Multivariate Cox proportional hazards model showed that elevated CXCL12a independently predicted (P&lt;0.05) earlier death in PAH with a hazard ratio (95% confidence interval) of 2.25 (1.01-5.00). In the largest subset by WHO functional class (Class 3, 65% of patients) elevated CXCL12a independently predicted (P&lt;0.05) earlier death, hazard ratio 2.27 (1.05-4.89). Our data show that elevated concentrations of circulating CXCL12a in PAH predicted poorer survival. Furthermore, elevated circulating CXCL12a was an independent risk factor for death that could potentially be included in a prognostic model and guide therapy

McCullagh, Brian N.

Costello, Christine M.

Li, Lili

O'Connell, Caroline

Codd, Mary

McLoughlin, Paul

et al.

Research Repository at University College Dublin

Elevated plasma CXCL12a is associated with a poorer prognosis in pulmonary arterial hypertension

O\u27Connell, Caroline

Irish Universities

Brian N McCullagh

Christine M Costello

Caroline O'Connell

David G Kiely

Directory of Open Access Journals

PLoS ONE

Elevated plasma CXCL12α is associated with a poorer prognosis in pulmonary arterial hypertension.

Research Repository UCD

Crossref

<div>RationaleRecent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12α were elevated in patients with PAH and related to mortality.MethodsPlasma samples were collected from patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with connective tissue diseases (CTD-PAH) attending two pulmonary hypertension referral centres (n = 95) and from age and gender matched healthy controls (n = 44). Patients were subsequently monitored throughout a period of five years.ResultsCXCL12α concentrations were elevated in PAH groups compared to controls (P<0.05) and receiver-operating-characteristic analysis showed that plasma CXCL12α concentrations discriminated patients from healthy controls (AUC 0.80, 95% confidence interval 0.73-0.88). Kaplan Meier analysis indicated that elevated plasma CXCL12α concentration was associated with reduced survival (P<0.01). Multivariate Cox proportional hazards model showed that elevated CXCL12α independently predicted (P<0.05) earlier death in PAH with a hazard ratio (95% confidence interval) of 2.25 (1.01-5.00). In the largest subset by WHO functional class (Class 3, 65% of patients) elevated CXCL12α independently predicted (P<0.05) earlier death, hazard ratio 2.27 (1.05-4.89).ConclusionsOur data show that elevated concentrations of circulating CXCL12α in PAH predicted poorer survival. Furthermore, elevated circulating CXCL12α was an independent risk factor for death that could potentially be included in a prognostic model and guide therapy.</div

Brian N. McCullagh (719579)

Christine M. Costello (719580)

Lili Li (42450)

Caroline O’Connell (719581)

Mary Codd (719582)

Allan Lawrie (276358)

Allison Morton (719583)

David G. Kiely (719584)

Robin Condliffe (719585)

Charles Elliot (719586)

Paul McLoughlin (494617)

Sean Gaine (719587)

The Francis Crick Institute

McCullagh, B.N.

Costello, C.M.

Li, L.

O'Connell, C.

Codd, M.

Lawrie, A.

Morton, A.

Kiely, D.G.

Condliffe, R.

Elliot, C.

McLoughlin, P.

Gaine, S.

White Rose Research Online