| Autor: |
Abreu S, Keith Burling, N W Morrell, John Wort, Joanna Pepke-Zaba, Emilia M. Swietlik, Elaine Soon, Peter Barker, Stefan Gräf, M Schwiening, Stefan J. Marciniak, Treacy C, Pandya D |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.05.05.21253970 |
| Popis: |
BackgroundPulmonary arterial hypertension (PAH) covers a range of life-limiting illnesses characterized by increased pulmonary arterial pressures leading to right heart failure and death, if untreated. 15-25% of patients have genetic mutations, the most common affecting bone morphogenetic protein receptor type 2 (BMPR2). The aim was to define an inflammatory cytokine profile in BMPR2-mutation positive patients and analyze their influence on survival.MethodsLevels of cytokines were measured in plasma samples from BMPR2-mutation positive patients (BMPR2mut, n=54), patients without any driving mutations (n=54), and healthy controls (n=56) recruited from the United Kingdom cohort.FindingsBMPR2-mutation positive patients and patients without mutations had high levels of interleukin-6, interleukin-8, tumor necrosis factor-α, and vascular endothelial growth factor-A compared to controls. Only BMPR2-mutation carrying patients had higher G-CSF levels compared to controls. VEGF-A levels were substantially higher in patients without mutations compared to the BMPR2mut group. Interleukin-6 was a significant discriminator for mortality in the BMPR2mut cohort (cumulative survival with interleukin-6≥1.6pg/ml at 3 years was 65% compared to 96% with interleukin-6P=0·0013). N-Terminal pro-B-Type natriuretic peptide levels did not discriminate for survival in our BMPR2mut cohort (cumulative survival for patients with an NT-proBNP>130ng/ml at 3 years was 76% compared to 84% for patients with an NT-proBNP≤130ng/ml, P=0·37). NT-proBNP outperformed interleukin-6 in PAH without mutations.InterpretationBMPR2-mutation positivity has a direct impact not only on inflammatory profiles but also on effectiveness of prognostic biomarkers. In our BMPR2-mutation positive cohort IL-6 was the strongest prognostic biomarker and NT-proBNP failed to discriminate for survival.Key messagesWhat is the key question?Do pulmonary arterial hypertension patients who are BMPR2-mutation positive have a different cytokine signature than PAH patients without mutations?What is the bottom line?BMPR2-mutation positive and PAH patients without mutations display different patterns of cytokine elevation and these cytokines differ in the way they influence transplant-free survival.Why read on?In our cohort of BMPR2-mutation positive patients, IL-6 is the best prognostic biomarker while NT-proBNP failed to discriminate for survival – this implies that prognostic biomarkers and by inference treatments could be genotype-specific.Graphical AbstractTAKE HOME MESSAGEBMPR2-mutation positive patients have different inflammatory and growth factor profiles compared to PAH patients without mutations. Interleukin-6 is an effective biomarker for transplant-free survival in our cohort of BMPR2-mutation positive patients while NT-proBNP is ineffective. Conversely, NT-proBNP appears to be a more effective biomarker for pulmonary arterial patients without any mutations. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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