Selective induction of pentraxin 3, a soluble innate immune pattern recognition receptor, in infectious episodes in patients with haematological malignancy

doi:10.1016/j.clim.2004.03.012

Clinical Immunology

Volume 112, Issue 3, September 2004, Pages 221-224

https://doi.org/10.1016/j.clim.2004.03.012 Get rights and content

Abstract

Pentraxins are a superfamily of conserved proteins induced in response to microbial and inflammatory stimuli. Members of this family include C-reactive protein (CRP) and serum amyloid P component, collectively known as the classical short pentraxins, and the more recently discovered pentraxin 3 (PTX3), a member of the closely related subfamily of the long pentraxins. PTX3 has been shown to be produced in response to microbial infections, and highly elevated levels were reported in patients with sepsis. In this study, PTX3 levels were evaluated in sera of a group of patients with haematological malignancy. Our findings indicate that serum PTX3 was elevated in only 1/11 afebrile episodes, despite evidence of mucositis (median 1.39), in 10/10 episodes of blood stream or target organ infections (median 7.2) but, surprisingly, was normal in 5/5 episodes of invasive aspergillosis (median 1.39). The data suggest that serum PTX3 levels are elevated selectively in response to infection. These disparate responses require further study.

Introduction

Pentraxin 3 (PTX3) is the first identified member of the long pentraxin family of proteins. The long pentraxins differ from the classical short pentraxins, such as C-reactive protein (CRP), in having a long, unrelated N-terminal domain coupled to the C-terminal pentraxin domain. Unlike the short pentraxins which are produced in the liver in response to inflammatory stimuli, principally IL-6, PTX3 is released from endothelial, dendritic and macrophage cells following stimulation by pro-inflammatory signals such as TNFα, IL-1 and selected microbial moieties [1]. PTX3 appears to play a key role in the innate immune response to certain pathogens for which it has specific receptor properties. Elevated levels are found in myocardial infarction and in connective tissue disorders [1]. PTX3 levels correlate with disease severity in patients critically ill with sepsis [2]. Patients with haematological malignancy are at particular high risk for sepsis; PTX3 levels have not been explored in this patient population previously. We report some preliminary observations in these patients.

Section snippets

Patients and methods

This was a preliminary post hoc observational study involving a cohort of patients with haematological malignancy admitted to the Haematology Unit of Tawam Hospital, a cancer referral centre for the United Arab Emirates, over the period of May 2001 to November 2001, for induction chemotherapy. Patients received standard regimens of chemotherapy for their haematological disease, namely, for acute myeloid leukaemia (AML) induction idarubicin, cytarabine and etoposide; for acute lymphocytic

Results

The demographic and infection characteristics of the evaluable episodes are shown in Table 1. All patients developed neutropenia (<0.5 × 10⁹/l) for 10–14 days.

Twenty-six episodes were identified amongst 11 patients. Most patients had ≥2 distinct episodes characterised as follows: Group 1 (11 episodes), afebrile and non-infected; Group 2 (10 episodes), infections other than invasive aspergillosis; Group 3 (5 episodes), infections caused by invasive aspergillosis. The results of CRP and PTX3

Discussion

Our observations suggest PTX3 concentrations do not become elevated in patients undergoing chemotherapy for haematological malignancy, even when neutropenic with mucositis (Group 1), unless the patients develop infection (Group 2). Since chemotherapy induces substantial apoptosis, particularly of the gastrointestinal tract (GIT), which is associated with considerable pro-inflammatory cytokine signaling, for example, TNFα, it is surprising that serum PTX3 levels are not elevated. On the

Acknowledgements

This study was supported by grants from the Terry Fox Cancer Research Fund (BR and ME) and the European Commission and Associazione per la Ricerca sul Cancro (AM).

References (8)

M. Ellis et al.
Recombinant interleukin 11 and bacterial infection in patients with haematological malignancy undergoing chemotherapy: a double-blind placebo-controlled randomized trial
Lancet
(2003)
P. Rovere et al.
The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells
Blood
(2000)
A. Mantovani et al.
Pentraxin 3, a non-redundant soluble pattern recognition receptor involved in innate immunity
Vaccine
(2003)
B. Muller et al.
Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients
Crit. Care Med.
(2001)

There are more references available in the full text version of this article.

Cited by (19)

Pentraxin 3 in neonates with and without diagnosis of pulmonary hypertension
2017, Clinical Biochemistry
Citation Excerpt :
CRP is a short pentraxin originated from liver, whereas PTX3 is a long pentraxin that is highly expressed in the heart and synthesized by vascular endothelial cells and macrophages [5–8]. PTX3 has a well-established role in the innate immune response to infection [9,10]. Serum level of PTX3 has a correlation with severity of infectious disease and can be used as an independent prognostic biomarker in bacteriemia and fatal diseases [11,12].
Pentraxin 3 is a novel biomarker produced by vascular endothelial cells and macrophages. In recent studies involving adults, pentraxin 3 has been introduced as a reliable biomarker in the evaluation of cardiovascular disease and pulmonary hypertension. This study was conducted with an aim to measure the level of pentraxin 3 in neonates with pulmonary hypertension and comparing with normal healthy controls.
In a case-control study, plasma pentraxin 3 levels were evaluated in 3 groups of neonates including neonates with pulmonary arterial hypertension (PAH), neonates with congenital heart disease without pulmonary arterial hypertension (CHD-PAH) and normal healthy neonates.
Plasma pentraxin 3 levels in 72 neonates (21 in PAH, 19 in CHD-PAH, and 32 in control group) were measured. Demographic characteristics had no significant statistical difference among the 3 groups. Pentraxin 3 levels in PAH group was significantly higher than CHD-PAH and control groups (2.12 ± 2.32 vs. 0.58 ± 0.57 and 1.03 ± 1.38 ng/mL, P = 0.008, respectively). No significant correlation was found between concentrations of pentraxin 3 and cardiac ejection fractions between PAH and CHD-PAH (r = 0.009, P = 0.97). However, significant positive correlation was detected between PTX3 concentrations and pulmonary pressures between these two groups (r = 0.499, P = 0.001).
Results from our study showed that pentraxin 3 levels were increased in newborn infants with pulmonary hypertension. Plasma pentraxin 3 could be considered as a novel adjunct diagnostic tool in the evaluation of pulmonary hypertension in combination with echocardiography or as a diagnostic tool when echocardiography is not readily available for confirmation of increased pulmonary pressure.
PTX3 predicts severe disease in febrile patients at the emergency department
2010, Journal of Infection
Citation Excerpt :
Yet, the precise clinical implications of these biological functions of PTX3 are still insufficiently understood. Increased levels of PTX3 have been reported in multiple inflammatory conditions.9–12 In critically ill patients with sepsis, highly increased levels were detected, which correlated with disease severity, ranging from the systemic inflammatory response syndrome (SIRS) to sepsis and septic shock.13
The long pentraxin PTX3 is a promising marker of disease severity in severely ill patients. In order to identify patients warranting critical care as quickly as possible, we investigated the value of PTX3 as a biomarker for disease severity in patients presenting with fever at the emergency department.
Levels of PTX3 were measured in 211 febrile patients at the emergency and the levels were linked to markers of disease severity including admittance to a special care unit, bloodstream infection and congestive heart failure.
In comparison to median baseline levels of 2.30 ng/ml (interquartile range 1.66–3.67 ng/ml), levels of PTX3 were significantly elevated in patients admitted to the intensive-/medium care unit (median value 44.4 ng/ml, interquartile range 13.6–105.9 ng/ml) and in patients referred to the ward (median value 14.2 ng/ml, interquartile range 7.01–25.1 ng/ml). In addition, PTX3 was associated with duration of hospital stay and acute congestive heart failure. The levels were predictive for bloodstream infection (AUC = 0.71; 95% CI 0.62–0.81).
PTX3 may be a useful marker for differentiation of patients with severe disease in patients presenting with fever to the emergency department.
The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens
2006, Blood
Citation Excerpt :
PTX3 was first identified as an IL-1β-inducible gene in endothelial cells4 and a TNF-α-stimulated gene in fibroblasts.5 Elevated levels of PTX3 have been reported in infectious and inflammatory conditions.6-11 Mouse models indicate a nonredundant role of PTX3 in immunity to fungal infections, especially pulmonary aspergillosis, and in female fertility.12-14
Pentraxins are soluble pattern recognition receptors with a dual role: protection against extracellular microbes and autoimmunity. The mechanisms by which they accomplish these tasks are not yet fully understood. Here we show that the prototypic long pentraxin PTX3 is specifically recruited at both sides of the phagocytic synapse between dendritic cells (DCs) and dying cells and remains stably bound to the apoptotic membranes (estimated half-time > 36 hours). Apoptotic cells per se influence the production of PTX3 by maturing DCs. When both microbial stimuli and dying cells are present, PTX3 behaves as a flexible adaptor of DC function, regulating the maturation program and the secretion of soluble factors. Moreover a key event associated with autoimmunity (ie, the cross-presentation of epitopes expressed by apoptotic cells to T cells) abates in the presence of PTX3, as evaluated using self, viral, and tumor-associated model antigens (vinculin, NS3, and MelanA/MART1). In contrast, PTX3 did not influence the presentation of exogenous soluble antigens, an event required for immunity against extracellular pathogens. These data suggest that PTX3 acts as a third-party agent between microbial stimuli and dying cells, contributing to limit tissue damage under inflammatory conditions and the activation of autoreactive T cells.
Second-trimester maternal serum markers in the prediction of preeclampsia
2017, Journal of Perinatal Medicine
Selected inflammatory markers in the diagnosis and monitoring of infections in children treated for hematological malignancies
2015, Biomarkers in Medicine
Biomarkers of necrotising soft tissue infections: Aspects of the innate immune response and effects of hyperbaric oxygenation-the protocol of the prospective cohort BIONEC study
2015, BMJ Open

View all citing articles on Scopus

View full text

Rapid CommunicationSelective induction of pentraxin 3, a soluble innate immune pattern recognition receptor, in infectious episodes in patients with haematological malignancy

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Acknowledgements

Lancet

Blood

Pentraxin 3, a non-redundant soluble pattern recognition receptor involved in innate immunity

Vaccine

Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients

Crit. Care Med.

Rapid Communication
Selective induction of pentraxin 3, a soluble innate immune pattern recognition receptor, in infectious episodes in patients with haematological malignancy