The Long Pentraxin 3 and Its Role in Autoimmunity

doi:10.1016/j.semarthrit.2008.03.006

Seminars in Arthritis and Rheumatism

Volume 39, Issue 1, August 2009, Pages 38-54

https://doi.org/10.1016/j.semarthrit.2008.03.006 Get rights and content

Objectives

To review the physiological and physiopathological roles of pentraxin 3 (PTX3), focusing on autoimmunity and vascular pathology.

Methods

A systematic literature review using the keywords “pentraxin 3,” “innate immunity,” “apoptosis,” “autoimmunity,” and “endothelial dysfunction” from 1990 to 2007 was performed. All relevant articles and pertinent secondary references in English were reviewed.

Results

PTX3 has a large number of multiple functions in different contexts. PTX3 plays an important role in innate immunity, inflammation, vascular integrity, fertility, pregnancy, and also in the central nervous system. In innate immunity, its normal function is to increase the immune response to selected pathogens while also exerting control over potential autoimmune reactions. It maintains a tightly homeostatic equilibrium in the local immune microenvironment by avoiding an exaggerated immune response and controlling peripheral tolerance to self-antigens. In contrast, in some autoimmune diseases, PTX3 appears to be involved in the development of autoimmune phenomena. A possible explanation for these apparent paradoxical functions may be related to the highly polymorphic PTX3 gene.

Conclusion

PTX3 is physiologically a protective molecule. However, in several autoimmune diseases PTX3 appears to facilitate the development of autoimmunity. The PTX3 gene could influence the development of autoimmune reactions and vascular involvement in human pathology.

Section snippets

Methods

PubMed and MEDLINE databases were researched for the key words “pentraxin 3,” “innate immunity,” “apoptosis,” “autoimmunity,” and “endothelial dysfunction” from 1990 to 2007. All relevant articles in English and their pertinent secondary references were also reviewed. Our approach was to find all information about PTX3 and its role in innate immunity and in autoimmune diseases.

Molecular Structure

The PTX3 protein is 381 amino acids long including a signal peptide of 17 amino acids. The mature secreted protein has a predicted molecular weight of 40,165 D and an apparent molecular mass which corresponds to a decamer (13). PTX3 consists of 203 amino acids, composed of a C-terminal, pentraxin-like domain coupled with an N-terminal portion of 178 amino acids unrelated to other known proteins (14). PTX3 is much longer than SAP and CRP at its NH2 terminus portion (15) (Fig. 1).

The crystal

Discussion

The evidence suggests that PTX3 is a two-edged sword having both a protective effect against autoimmunity and favoring autoimmune reactions, depending on milieu, disposal structure, cytokine profile, and gene variants. Short pentraxin polymorphisms have been associated with accelerated atherosclerosis (101) and with an increased occurrence of vascular arterial events in patients with autoimmune diseases (102). We hypothesize that PTX3 gene polymorphisms may be associated with the occurrence of

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Long-chain pentraxin 3 possesses agglutination activity and plays a role in host defense against bacterial infection in Oreochromis niloticus
2023, Developmental and Comparative Immunology
Pentraxin 3 (PTX3) is a soluble pattern recognition molecule in the innate immune system that has multiple functions. It is involved in resisting pathogen infection. However, the functions of PTX3 in teleost fish are not well understood. In this study, we identified and characterized PTX3 in Nile tilapia (Oreochromis niloticus) (OnPTX3). The open reading frame of OnPTX3 was found to be 1305 bp, encoding 434 aa. We conducted spatial mRNA expression analysis and found that the expression of OnPTX3 was significantly increased after infection with Streptococcus agalactiae and Aeromonas hydrophila, both in vivo and in vitro. We also observed that recombinant OnPTX3 protein could bind and agglutinate bacterial pathogen. Furthermore, OnPTX3 enhanced the phagocytosis of bacteria (S. agalactiae and A. hydrophila) by head kidney macrophages. Additionally, OnPTX3 was found to influence the expression of inflammatory cytokines, suggesting its involvement in the regulation of the inflammatory response. Moreover, OnPTX3 was shown to promote complement-mediated hemolysis and possess antibacterial activity. In conclusion, our research demonstrates that OnPTX3 has bacterial binding and agglutination activities, enhances phagocytosis, and regulates inflammation. It plays a crucial role in the defense of Nile tilapia against pathogenic bacteria, providing valuable insights for the prevention and control of aquatic diseases in the future.
The pentraxin family in autoimmune disease
2023, Clinica Chimica Acta
The pentraxins represent a family of multifunctional proteins composed of long and short pentamers. The latter includes serum amyloid P component (SAP) and C-reactive protein (CRP) whereas the former includes neuronal PTX1 and PTX2 (NPTX1 and NPTX2, respectively), PTX3 and PTX4. These serve as a bridge between adaptive immunity and innate immunity and a link between inflammation and immunity. Similarities and differences between long and short pentamers are examined and their roles in autoimmune disease are discussed. Increased CRP and PTX3 could indicate the activity of rheumatoid arthritis, systemic lupus erythematosus or other autoimmune diseases. Mechanistically, CRP and PTX3 may predict target organ injury, regulate bone metabolic immunity and maintain homeostasis as well as participate in vascular endothelial remodeling. Interestingly, PTX3 is pleiotropic, being involved in inflammation and tissue repair. Given the therapeutic potential of PTX3 and CRP, targeting these factors to exert a beneficial effect is the focus of research efforts. Unfortunately, studies on NPTX1, NPTX2, PTX4 and SAP are scarce and more research is clearly needed to elaborate their potential roles in autoimmune disease.
Serum from half of patients with immune thrombocytopenia triggers macrophage phagocytosis of platelets
2023, Blood Advances
Humoral antiplatelet factors, such as autoantibodies, are thought to primarily clear platelets by triggering macrophage phagocytosis in immune thrombocytopenia (ITP). However, there are few studies characterizing the capacity and mechanisms of humoral factor–triggered macrophage phagocytosis of platelets using specimens from patients with ITP. Here, we assessed sera from a cohort of 24 patients with ITP for the capacity to trigger macrophage phagocytosis of normal donor platelets and characterized the contribution of humoral factors to phagocytosis. Sera that produced a phagocytosis magnitude greater than a normal human serum mean + 2 standard deviations were considered phagocytosis-positive. Overall, 42% (8/19) of MHC I alloantibody-negative ITP sera were phagocytosis-positive. The indirect monoclonal antibody immobilization of platelet antigens assay was used to detect immunoglobulin G (IgG) autoantibodies to glycoproteins (GP)IIb/IIIa, GPIb/IX, and GPIa/IIa. Autoantibody-positive sera triggered a higher mean magnitude of phagocytosis than autoantibody-negative sera. Phagocytosis correlated inversely with platelet counts among autoantibody-positive patients but not among autoantibody-negative patients. Select phagocytosis-positive sera were separated into IgG-purified and -depleted fractions via protein G and reassessed for phagocytosis. Phagocytosis was largely retained in the purified IgG fractions. In addition, we assessed serum concentrations of C-reactive protein, serum amyloid P, and pentraxin 3 as potential phagocytosis modulators. Pentraxin 3 concentrations correlated inversely with platelet counts among patients positive for autoantibodies. Taken together, sera from approximately half of the patients with ITP studied triggered macrophage phagocytosis of platelets beyond a normal level. An important role for antiplatelet autoantibodies in phagocytosis is supported; a role for pentraxins such as pentraxin 3 may be suggested.
Lessons from Cardiac and Vascular Biopsies from Patients with and without Inflammatory Rheumatic Diseases
2023, Rheumatic Disease Clinics of North America
Molecular insight into pentraxin-3: Update advances in innate immunity, inflammation, tissue remodeling, diseases, and drug role
2022, Biomedicine and Pharmacotherapy
Citation Excerpt :
The pro-apoptotic markers tested in the brain tissues of mice with Parkinson's disease following human recombinant PTX3(hrPTX3) treatment showed that hrPTX3 could prevent apoptosis and degeneration of the dopaminergic neurons [119]. PTX3 is a crucial mediator in innate immunity against selected pathogens, including bacteria, viruses, and fungi [120,121]. Human and murine PTX3 could bind to certain influenza virus strains and mediate a host of antiviral activities, including inhibition of hemagglutination, neutralization of virus infectivity, and inhibition of viral neuraminidase [69].
Pentraxin-3 (PTX3) is the prototype of the long pentraxin subfamily, an acute-phase protein consisting of a C-terminal pentraxin domain and a unique N-terminal domain. PTX3 was initially isolated from human umbilical vein endothelial cells and human FS-4 fibroblasts. It was subsequently found to be also produced by synoviocytes, chondrocytes, osteoblasts, smooth muscle cells, myeloid dendritic cells, epithelial cells, and tumor cells. Various modulatory factors, such as miRNAs, cytokines, drugs, and hypoxic conditions, could regulate the expression level of PTX3. PTX3 is essential in regulating innate immunity, inflammation, angiogenesis, and tissue remodeling. Besides, PTX3 may play dual (pro-tumor and anti-tumor) roles in oncogenesis. PTX3 is involved in the occurrence and development of many non-cancerous diseases, including COVID-19, and might be a potential biomarker indicating the prognosis, activity,and severity of diseases. In this review, we summarize and discuss the potential roles of PTX3 in the oncogenesis and pathogenesis of non-cancerous diseases and potential targeted therapies based on PTX3.
IgG anti-Pentraxin 3 antibodies are a novel biomarker of ANCA-associated vasculitis and better identify patients with eosinophilic granulomatosis with polyangiitis
2021, Journal of Autoimmunity
Citation Excerpt :
Pentraxins are soluble pattern recognition receptors which belong to the innate immune system and are involved in the clearance of pathogens and apoptotic cells [4]. Pentraxin 3 (PTX3) is part of the long-pentraxin family and is produced and released by different immune-competent or resident cell types upon inflammatory stimuli [5]. Preformed PTX3 is natively stored in neutrophil granules, similarly to PR3 and MPO, and can partially localize in neutrophil extracellular traps (NETs) [6].
To investigate prevalence of anti-Pentraxin 3 (PTX3) antibodies in sera of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients.
Anti-PTX3 and PTX3 levels were analysed by enzyme-linked immunosorbent assays in sera from unselected patients with AAV and compared with patients with systemic lupus erythematosus (SLE, n = 130), other connective tissue diseases (CTDs, n = 97) and matched healthy controls (n = 97). Optical density (OD) cut-off for positive anti-PTX3 antibodies was determined by ROC curve analysis and set as 0.234. Indirect immunofluorescence (IIF) on fixed human granulocytes was used to analyze the fluorescence pattern of anti-PTX3 antibodies. Liquid-phase inhibition tests were conducted to assess potential interferences.
We included 101 AAV patients (females 58%, median age 60[51–69] years) affected either with granulomatosis with polyangiitis (GPA, n = 51), microscopic polyangiitis (MPA, n = 12) or eosinophilic granulomatosis with polyangiitis (EGPA, n = 38). Anti-PTX3 antibodies were detected in 29.7% AAV patients, being significantly higher than in healthy controls (p < 0.001) and CTDs (p = 0.030) but lower than in SLE (p = 0.004). Anti-PTX3 antibody prevalence was 44.7% in EGPA, 25% in MPA and 19% in GPA (p = 0.034). Among ANCA negative patients, 35.7% displayed positive anti-PTX3 antibodies. Anti-PTX3 were associated with a lower prevalence of systemic (p = 0.002), ear-nose-throat (p = 0.006) and renal manifestations (p = 0.016). Anti-PTX3 antibodies were characterized by a specific IIF pattern on fixed granulocytes. PTX3 serum levels resulted lower in AAV than healthy controls (p < 0.001). PTX3 inhibited anti-PTX3 binding in a dose-dependent manner.
Anti-PTX3 autoantibodies appear a promising novel biomarker of AAV, especially EGPA.

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ImmunityThe Long Pentraxin 3 and Its Role in Autoimmunity

Objectives

Methods

Results

Conclusion

Section snippets

Methods

Molecular Structure

Discussion

Blood

Curr Opin Immunol

J Biol Chem

Structure

J Biol Chem

J Biol Chem

J Dermatol Sci

Blood

J Biol Chem

Blood

Blood

Vaccine

Autoimmun Rev

Blood

Cytokine Growth Factor Rev

J Biol Chem

J Biol Chem

Immunity

Microbes Infect

J Mol Biol

J Biol Chem

Am J Cardiol

Kidney Int

J Neuroimmunol

Neuroscience

Microbes Infect

Rheum Dis Clin North Am

J Autoimmun

J Lipid Res

Atherosclerosis

Rheum Dis Clin North Am

Hamster female proteinA new Pentraxin structurally and functionally similar to C-reactive protein and amyloid P component

J Exp Med

TNF alpha induced long pentraxin PTX3 expression in human lung epithelial cells via JNK

J Immunol

Nonredundant role of the long pentraxin PTX3 in anti-fungal innate immune response

Nature

Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility

Mol Endocrinol

Protective molecules—C-reactive protein (CRP), serum amyloid P (SAP), pentraxin3 (PTX3), mannose-binding lectin (MBL), and apolipoprotein A1 (Apo A1), and their autoantibodies: prevalence and clinical significance in autoimmunity

J Clin Immunol

Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility

Annu Rev Immunol

Establishment of a high sensitivity plasma assay for human pentraxin 3 as a marker for unstable angina pectoris

Arterioscler Thromb Vasc Biol

PTX3

A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans Circulation

Prognostic significance of the long pentraxin PTX3 in acute myocardial infarction

Circulation

PTX3 in small vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation

Arthritis Rheum

Membrane and soluble pattern recognition receptors: unique functions of the long pentraxin PTX3

Clin Exp All Rev

Structure and function of the long pentraxin PTX3 glycosidic moiety: fine-tuning of the interaction with C1q and complement activation

Biochemistry

Biochemical and functional characterization of the interaction between pentraxin 3 and C1q

Eur J Immunol

A neuraminidase from Streptococcus pneumoniae has the features of a surface protein

Infect Immun

Pentraxin 3 inhibits fibroblast growth factor 2-dependent activation of smooth muscle cells in vitro and neointima formation in vivo

Arterioscler Thromb Vasc Biol

Apoptosis and autoimmunity: when apoptotic cells break their silence

Curr Rheumatol Rep

Apoptosis and autoimmunity

Immunol Res

Blebs and apoptotic bodies are B cell autoantigens

J Immunol

Serum amyloid P component binds to late apoptotic cells and mediates their uptake by monocyte derived macrophages

Arthritis Rheum

Immunity
The Long Pentraxin 3 and Its Role in Autoimmunity