Pentraxin-3 levels are associated with vasculitis and disease activity in childhood-onset systemic lupus erythematosus

Abstract

Objectives

Childhood-onset systemic lupus erythematosus (cSLE) is a multisystemic autoimmune disease characterized by inflammatory organ damage by means of vasculitis. Pentraxin-3 (PTX3) is expressed locally at the sites of inflammatory processes, predominantly from endothelial cells. In adult studies, PTX3 has shown to be an indicator of active vasculitis both in large-vessel and small-vessel vasculitides, as well as in SLE. Moreover, in SLE it has found to be correlated with disease activity, and with some of the clinical manifestations and laboratory parameters. We aimed to ascertain if PTX3 might be a significant mediator in cSLE and if it might indicate active vasculitis during the course of the disease.

Methods

Serum PTX3 levels were measured in 76 patients with cSLE and 41 healthy subjects. We have investigated its relation with disease activity, damage, clinical features, laboratory parameters and medications.

Results

Serum levels of PTX3 were found to be increased in cSLE compared to healthy controls (mean ± SD; 10.6 ± 8.2 ng/mL vs 2.7 ± 1.3 ng/mL, p < 0.001). PTX3 concentrations were also in correlation with SLEDAI-2K (r = 0.57, p < 0.001). When viewed from the clinical perspective, serum PTX3 levels were significantly higher only in patients with active vasculitis (p < 0.001), Raynaud phenomenon (p = 0.006) and mucocutaneous manifestations (p < 0.001). However, an association between PTX3 and age, age at disease onset, disease duration, complement levels, PedSDI score (pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), ESR, CRP, procalcitonin levels, anti-ds DNA antibody, anticardiolipin antibodies was not detected.

Conclusions

Patients with cSLE have increased levels of serum PTX3 compared to healthy controls. Thus, serum PTX-3 level might be a significant mediator in cSLE. Apart from these, the results support that PTX3 reflects active cutaneous vasculitis in cSLE and correlates with disease activity.

Keywords

Pentraxin-3 Childhood-onset systemic lupus erythematosus Biomarker SLEDAI Vasculitis

Get full access to this article

View all access options for this article.

References

Jennette

Falk

Bacon

et al.

2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65: 1–11.

Borgia

Silverman

. Childhood-onset systemic lupus erythematosus: An update. Curr Opin Rheumatol 2015; 27: 483–492.

Tarr

Derfalvi

Gyori

et al.

Similarities and differences between pediatric and adult patients with systemic lupus erythematosus. Lupus 2015; 24: 796–803.

Mantovani

Garlanda

Doni

Bottazzi

. Pentraxins in innate immunity: From C-reactive protein to the long pentraxin PTX3. J Clin Immunol 2008; 28: 1–13.

Shimada

Asanuma

Yokota

et al.

Pentraxin 3 is associated with disease activity but not atherosclerosis in patients with systemic lupus erythematosus. Mod Rheumatol 2014; 24: 78–85.

Fazzini

Peri

Doni

et al.

PTX3 in small-vessel vasculitides: An independent indicator of disease activity produced at sites of inflammation. Arthritis Rheum 2001; 44: 2841–2850.

Tombetti

Di Chio

Sartorelli

et al.

Systemic pentraxin-3 levels reflect vascular enhancement and progression in Takayasu arteritis. Arthritis Res Ther 2014; 16: 479–479.

van Rossum

Pas

Fazzini

et al.

Abundance of the long pentraxin PTX3 at sites of leukocytoclastic lesions in patients with small-vessel vasculitis. Arthritis Rheum 2006; 54: 986–991.

Cieślik

Hrycek

. Pentraxin 3 as a biomarker of local inflammatory response to vascular injury in systemic lupus erythematosus. Autoimmunity 2015; 48: 242–250.

10.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725–1725.

11.

Gladman

Ibanez

Urowitz

. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29: 288–291.

12.

Gutierrez-Suarez

Ruperto

Gastaldi

et al.

A proposal for a pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index based on the analysis of 1,015 patients with juvenile-onset systemic lupus erythematosus. Arthritis Rheum 2006; 54: 2989–2996.

13.

Pang

Tan

et al.

Pentraxin 3 is closely associated with tubulointerstitial injury in lupus nephritis: A large multicenter cross-sectional study. Medicine (Baltimore) 2016; 95: e2520–e2520.

14.

Assandri

Monari

Colombo

Dossi

Montanelli

. Pentraxin 3 plasma levels and disease activity in systemic lupus erythematosus. Autoimmune Dis 2015; 2015: 354014–354014.

15.

Skare

Nisihara

Ramos

Utiyama

Messias-Reason

. Pentraxin-3 levels in systemic lupus erythematosus: Association with cumulative damage but not with disease activity. Joint Bone Spine 2015; 82: 466–467.

16.

Hollan

Bottazzi

Cuccovillo

et al.

Increased levels of serum pentraxin 3, a novel cardiovascular biomarker, in patients with inflammatory rheumatic disease. Arthritis Care Res (Hoboken) 2010; 62: 378–385.

17.

Tsokos

. Systemic lupus erythematosus. N Engl J Med 2011; 365: 2110–2121.

18.

Drenkard

Villa

Reyes

Abello

Alarcon-Segovia

. Vasculitis in systemic lupus erythematosus. Lupus 1997; 6: 235–242.

19.

Pique

Palacios

Santana

. Leukocytoclastic vasculitis presenting as an erythema gyratum repens-like eruption on a patient with systemic lupus erythematosus. J Am Acad Dermatol 2002; 47: S254–S256.

20.

Ramos-Casals

Nardi

Lagrutta

et al.

Vasculitis in systemic lupus erythematosus: prevalence and clinical characteristics in 670 patients. Medicine (Baltimore) 2006; 85: 95–104.

21.

Bakst

Merola

Franks

Jr. Sanchez

. Raynaud’s phenomenon: Pathogenesis and management. J Am Acad Dermatol 2008; 59: 633–653.