Background Right heart catheterisation (RHC) is an important test for the diagnosis and subclassification of pulmonary hypertension (PH), one of the serious manifestations of systemic sclerosis (SSc). It provides haemodynamic information for diagnosis and management. Routine RHC in SSc cases with suspected PH permits blood sampling to explore plasma levels of key cytokines that may be markers of mediators of pulmonary arterial hypertension (PAH) pathogenesis.
Objectives This is an exploratory study to assess for associations between plasma cytokine levels and haemodynamic assessment from RHC in SSc patients.
Methods SSc patients undergoing routine RHC were recruited. Indications for referral included suspected PH, or those on treatment for established PH for assessment of response to therapy. Blood samples were collected during RHC in consented patients. Demographic and clinical data were obtained. Haemodynamic data from RHC including mean right atrial pressure (mRAP), mean pulmonary arterial pressure (mPAP), pulmonary capillary wedge pressure (PCWP), pulmonary vascular resistance (PVR), cardiac output (CO) and cardiac index (CI) were recorded. Plasma samples were analysed using a bead-based multiplex platform for IL1b, IL4, IL6, IL10, IL17A, IL17F, IL21, IL22, IL23, IL25, IL31, IL33, IFNg, sCD40L and TNFa (Bio-Rad Pro Assays). Plasma from a small group of healthy controls were also analysed for comparison. For analytes found to be below the lower limit of detection of the assays, they were assumed to be equal to the lower limit of the detection as per the assay's protocol.
Results 32 SSc patients were recruited. Their mean age was 59.4-year-old, and 31 of them (97%) were female. Most (n=29, 91%) had limited cutaneous SSc. The commonest antibody was anti-centromere antibody (n=16, 55%), followed by anti-U3RNP antibody (n=4, 14%). None of these patients had significant pulmonary fibrosis (≥20% involvement on HRCT thorax scan). PAH, defined as mPAP ≥25mmHg & PCWP ≤15mmHg, was diagnosed at RHC in 26 patients (81%).
Among the proteins tested, only the level of sCD40L was significantly different among the three groups, namely SSc with PH, SSc without PH and healthy controls (p=0.008). sCD40L was also the only biomarker which was significant higher among patients with SSc (with and without PH) than healthy controls (p=0.0284).
Interestingly, there was a weak negative correlation between sCD40L and mPAP (correlation coefficient=-0.35, p=0.0486). There was a moderately strong positive correlation between mRAP and IL4 (correlation coefficient=0.57, p=0.0006) and IL10 (correlation coefficient=0.51, p=0.0028). We found no evidence for association between any of the biomarkers and cardiac output, cardiac index, PCWP or PVR.
Conclusions Our data suggest that some individual plasma proteins may correlate with specific RHC haemodynamic parameters. Future studies will extend these findings and explore whether combining multiple analytes may give stronger non-invasive prediction of relevant haemodynamic variables and could be used in detection or monitoring of PAH in SSc.
Proc Natl Acad Sci USA. 2015 May19;122(20):E2677–86.
Ann Am Thorac Soc. 2016 Jan;13(1)25–30.
Disclosure of Interest None declared