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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00240

Elevated systemic pentraxin-3 is associated with complement consumption in the acute phase of thrombotic microangiopathies

  • 1MTA-SE Immunological and Haematological Research Group, 3rd Department of Internal Medicine, Semmelweis University, Hungary
  • 2Department of Immunology, Eötvös Loránd University, Hungary
  • 3Department of Haematology and Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute for Hematology and Infectious Diseases, Hungary
  • 41st Department of Paediatrics, Semmelweis University, Hungary
  • 5MTA-SE Paediatrics and Nephrology Research Group,1st Department of Paediatrics, Semmelweis University, Hungary

Pentraxin-3 (PTX3) and C-reactive protein (CRP) have been shown to regulate complement activation in vitro, but their role has not been investigated in complement consumption in vivo. Thrombotic microangiopathies (TMA) are often accompanied by complement overactivation and consumption, therefore we analyzed the relation of the systemic pentraxin levels to the complement profile, laboratory parameters and clinical outcome of TMA patients. We determined the PTX3 and CRP levels, complement factor and activation product concentrations in blood samples of 171 subjects with the diagnosis of typical hemolytic uremic syndrome (STEC-HUS) (N=34), atypical HUS (aHUS) (N=44), secondary TMA (N=63), thrombotic thrombocytopenic purpura (TTP) (N=30) and 69 age-matched healthy individuals. Clinical data, blood count and chemistry were collected from medical records. To determine the in vitro effect of PTX3 on alternative pathway (AP) activation, sheep red blood cell-based hemolytic assay and AP activity ELISA were used. We found that PTX3 levels were elevated in the acute phase of STEC-HUS, aHUS and secondary TMA, whereas PTX3 elevation was exceptional is TTP. Conversely, a significantly higher median CRP was present in all patient groups compared to controls. PTX3, but not CRP was associated with signs of complement consumption in vivo, and PTX3 significantly decreased the AP hemolytic activity in vitro. Our results provide a detailed description of acute phase-TMA patients’ complement profile linked to changes in the systemic pentraxin levels that may support further molecular studies on the function of PTX3 in disease pathogenesis and add to the laboratory assessment of complement consumption in TMA.

Keywords: Pentraxin-3 (PTX3), C-reactive protein (CRP), Thrombotic Microangiopathies (TMA), Complement consumption, Thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS)

Received: 30 Sep 2018; Accepted: 28 Jan 2019.

Edited by:

Barbara Bottazzi, Humanitas Clinical and Research Center, Milan University, Italy

Reviewed by:

Antonio Inforzato, Istituto Clinico Humanitas
Giuseppe Remuzzi, Istituto Di Ricerche Farmacologiche Mario Negri, Italy
Marie-Agnes DRAGON-DUREY, Université Paris Descartes, France  

Copyright: © 2019 Trojnar, Józsi, Szabó, Réti, Farkas, Kelen, Reusz, Szabó, Garam, Mikes, Sinkovits, Mező, Csuka and Prohászka. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Eszter Trojnar, MTA-SE Immunological and Haematological Research Group, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary, eszter.trojnar@gmail.com