PTX3 Intercepts Vascular Inflammation in Systemic Immune-Mediated Diseases

Abstract

PTX3 is a prototypic soluble pattern recognition receptor, expressed at sites of inflammation and involved in regulation of the tissue homeostasis. PTX3 systemic levels increase in many (but not all) immune-mediated inflammatory conditions. Research on PTX3 as a biomarker has so far focused on single diseases. Here, we performed a multi-group comparative study with the aim of identifying clinical and pathophysiological phenotypes associated with PTX3 release. PTX3 concentration was measured by ELISA in the plasma of 366 subjects, including 96 patients with giant cell arteritis (GCA), 42 with Takayasu's arteritis (TA), 10 with polymyalgia rheumatica (PMR), 63 with ANCA-associated systemic small vessel vasculitides (AAV), 55 with systemic lupus erythematosus (SLE), 21 with rheumatoid arthritis (RA) and 79 healthy controls (HC). Patients with SLE, AAV, TA and GCA, but not patients with RA and PMR, had higher PTX3 levels than HC. PTX3 concentration correlated with disease activity, acute phase reactants and prednisone dose. It was higher in females, in patients with recent-onset disease and in those with previous or current active vasculitis at univariate analysis. Active small- or large- vessel vasculitis were the main independent variables influencing PTX3 levels at multivariate analysis. High levels of PTX3 in the blood can contribute to identify an increased risk of vascular involvement in patients with systemic immune-mediated diseases.

Keywords: ANCA associated small vessel vasculitis; PTX3; Takayasu arteritis; autoimmunity; giant cell arteritis; intravascular immunity; lupus; rheumatoid arthritis.

Figure 1

PTX3 levels among different diseases. PTX3 plasma levels were compared among patients with multiple distinct autoimmune diseases and HC. Pairwise comparisons among groups are reported below. Patients with PMR and RA did not differ from HC, whereas patients with other immune-mediated diseases showed significantly higher levels of PTX3 compared to patients with RA and HC. Patients with SLE had higher levels of PTX3 compared to patients with large- (TA, GCA) and small-vessel vasculitides (AAV). AAV, ANCA-associated vasculitides; GCA, giant cell arteritis; HC, healthy controls; PMR, polymyalgia rheumatica; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; TA, Takayasu's arteritis; ^*p < 0.05; ^**p < 0.01; ^***p < 0.001.

Figure 2

PTX3 levels and demographics. These panels show the existing differences in systemic expression of PTX3 by selected demographics. PTX3 levels were higher in females (A) and in patients with early-onset disease (B). ^*p < 0.05.

Figure 3

Correlations with PTX3 levels. PTX3 correlated with multiple disease and treatment-related variables at univariate analysis. (A) Depicts the linkage between increasing normalized activity score (Z-activity) and PTX3 plasma levels. (B) Shows the potential influence of corticosteroid treatment on PTX3 circulating levels.

Figure 4

PTX3 levels and disease phenotypes. In this multi-panel graph, differences in PTX3 plasma levels among phenotype groups are highlighted. PTX3 levels were higher in patients with active disease (A), but not with accrued irreversible damage (B). PTX3 was also higher in patients on corticosteroids (C). (D) Depicts the existing differences between patients with vs. without a history of vasculitis and between active or quiescent vasculitis at time of sampling. In (E,F) patients are stratified according to a history (E) or ongoing activity (F) of small- or large-vessel vasculitis associated with higher levels of PTX3 when compared to no vasculitis. ^*p < 0.05; ^**p < 0.01; ^***p < 0.001.