Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Endothelial Lineage Impairment and Increased PR3 Expression on Peripheral Cells of Endothelial Phenotype in Wegener's Granulomatosis.
Patschan, Susann, Patschan, Daniel, Henze, Elvira, Wessels, Johannes, Blaschke, Sabine, Anton Muller, Gerhard
Wegener's Granulomatosis (WG) is characterized by microvascular endothelial damage and by alterations of the endothelial progenitor cell (EPC) system. Interactions between anti-Proteinase 3 antibodies and their respective antigens (PR3) on neutrophils are pathogenetically relevant in WG. Aim of this study was (I) to analyze total circulating EPCs and regenerative activity of blood-dereived EPCs, and (II) to evaluate PR3 expression patterns on circulating myelomonocytic and endothelial cells in WG.
Blood samples from WG patients were analyzed for total and for Flk-1+ myolomonocytic cells (cytometric analysis). Healthy donors served as controls. For evaluating the proliferative activity of EPCs, a colony forming unit assay (CFU) was performed. PR3 expression by the cells was quantified by cytometric analysis. Serum Angiopoietin 1 and serum TNF-a were measured by ELISA technique.
A total of 21 healthy donors (12 female, 9 male [40.3 ±9.2 years]) and 31 WG patients (13 female, 18 male [59.2 ±15.3 years]) were included into the study. The total percentages of EPCs were not different between the two groups. WG patients displayed lower proliferate activity of EPCs (22.3 ±4.1 vs. 45.9 ±6.8, CFU-ECs, p=0.0027). In addition PR3 expression was significantly higher in the total as well as in the Flk-1+ (sub)population of myelomonocytic cells in WG (10.4 ±14.4% vs. 0.3 ±0.4%, p=0.02 bzw. 0.3 ±0.3% vs. 0.1 ±0.1%, p=0.04). Finally, WG patients showed lower mean serum levels of Angiopoietin 1 and higher mean serum levels of TNF-a as compared to controls (689 ±224 pg/ml vs. 1542 ±315 pg/ml, p=0.034 and 13 ±1 vs. 8.9 ±0.5 pg/ml, p=0.04), the serum levels of both cytokines did not linearily correlate with either clinical activity or the total number of circulating EPCs or the numbers of colonies formed (EPC regeneration).
In addition to reduced EPC regeneration and decreased serum levels of Angiopoietin 1, both indicating impairement of the endothelial system, patients with WG show significantly increased expression of PR3 in the total and in the Flk-1+ myelomonocytic cell population. These data imply, that PR3 could be involved in the pathogenesis of microvascular endothelial damage in patients with WG.
To cite this abstract, please use the following information:
Patschan, Susann, Patschan, Daniel, Henze, Elvira, Wessels, Johannes, Blaschke, Sabine, Anton Muller, Gerhard; Endothelial Lineage Impairment and Increased PR3 Expression on Peripheral Cells of Endothelial Phenotype in Wegener's Granulomatosis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2021