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Biomedicines
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Complement System as a Therapeutic Target
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Complement System as a Therapeutic Target

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 2929

Special Issue Editor

Prof. Dr. Janos Szebeni

E-Mail Website
Guest Editor
Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary
Interests: structure and non-target effects of mRNA-LNPs; anti-PEG antibodies; complement system/activation/inhibition; pharmacokinetics; immunotoxicity; adverse immunological side effects; hypersensitivity/allergic reactions; gene therapy; immune activation by nano-biopharmaceuticals; complement-activation-related pseudoallergy (CARPA);cytokine release/storm syndrome; in vitro/in vivo models of innate immune activation; infusion reactions/anaphylaxis; allergic/anaphylactic reactions to COVID vaccines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The complement system, the humoral arm of the innate immune system, plays a central role in antimicrobial defense and tissue homeostasis. Since its first description by Bordet and Ehrlich in the late 1890s, thousands of papers and hundreds of reviews detailed the structure and function of >30 soluble and membrane-bound complement proteins, activation pathways and scores of diseases wherein complement deficiency or undesirable activation are involved in the pathogenesis. For the latter cases, inhibitors of activation at different steps in the chain reaction provide promising therapeutic options, as shown by the preclinical and clinical trials with > 20 drug candidates to date. Four of them reached regulatory approval and, hence, clinical use (Eculizumab, Berinert, Ruconest, Cinryze), but little is known about many others that were, or currently are, in preclinical or Phase I-III trials. These include Compstatin derivatives (APL-1, APL-2, Cp40), Novartis' factor B and D inhibitors, Alnylam's CC5, Alexion's 1102, 1210 and 5500, Achillions' factor D inhibitor, Akaris' Coversin and many others. One goal of this volume is to focus on these approved, currently tested or failed complement inhibitors, whatever public information can be shared by those involved in their development. In addition, the volume gives space to articles dealing with naturally occurring complement inhibitors, i.e., various plant, fungal and microbial extracts. Original research data or comprehensive reviews on new developments in complement inhibition are also welcome, to make this volume represent the state-of-the-art in the field.

Prof. Dr. Janos Szebeni
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • anaphylatoxins
  • anaphylaxis
  • pseudoallergy
  • C3a
  • C5a
  • opsonization
  • classical pathway
  • alternative pathway
  • lectin pathway
  • inflammation
  • complement deficiency

Published Papers (2 papers)

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Research

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15 pages, 2403 KiB  
Article
Biomarkers of the Complement System Activation (C3a, C5a, sC5b-9) in Serum of Patients before and after Liver Transplantation
by Marta Budkowska, Ewa Ostrycharz, Natalia Maria Serwin, Łukasz Nazarewski, Elżbieta Cecerska-Heryć, Marta Poręcka, Paweł Rykowski, Radosław Pietrzak, Krzysztof Zieniewicz, Aldona Siennicka, Beata Hukowska-Szematowicz and Barbara Dołęgowska
Biomedicines 2023, 11(7), 2070; https://doi.org/10.3390/biomedicines11072070 - 23 Jul 2023
Viewed by 1498
Abstract
The liver has a huge impact on the functioning of our body and the preservation of homeostasis. It is exposed to many serious diseases, which may lead to the chronic failure of this organ, which is becoming a global health problem today. Currently, [...] Read more.
The liver has a huge impact on the functioning of our body and the preservation of homeostasis. It is exposed to many serious diseases, which may lead to the chronic failure of this organ, which is becoming a global health problem today. Currently, the final form of treatment in patients with end-stage (acute and chronic) organ failure is transplantation. The proper function of transplanted organs depends on many cellular processes and immune and individual factors. An enormous role in the process of acceptance or rejection of a transplanted organ is attributed to, among others, the activation of the complement system. The aim of this study was the evaluation of the concentration of selected biomarkers’ complement system activation (C3a, C5a, and sC5b-9 (terminal complement complex)) in the serum of patients before and after liver transplantation (24 h, two weeks). The study was conducted on a group of 100 patients undergoing liver transplantation. There were no complications during surgery and no transplant rejection in any of the patients. All patients were discharged home 2–3 weeks after the surgery. The levels of all analyzed components of the complement system were measured using the ELISA method. Additionally, the correlations of the basic laboratory parameters—C-reactive protein (CRP), hemoglobin (Hb), total bilirubin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGTP), and albumin—with the parameters of the complement system (C3a, C5a, and sC5b-9) were determined. In our study, changes in the concentrations of all examined complement system components before and after liver transplantation were observed, with the lowest values before liver transplantation and the highest concentration two weeks after. The direct increase in components of the complement system (C3a, C5a, and sC5b-9) 24 h after transplantation likely affects liver damage after ischemia-reperfusion injury (IRI), while their increase two weeks after transplantation may contribute to transplant tolerance. Increasingly, attention is being paid to the role of C3a and CRP as biomarkers of damage and failure of various organs. From the point of view of liver transplantation, the most interesting correlation in our own research was found exactly between CRP and C3a, 24 h after the transplantation. This study shows that changes in complement activation biomarkers and the correlation with CRP in blood could be a prognostic signature of liver allograft survival or rejection. Full article
(This article belongs to the Special Issue Complement System as a Therapeutic Target)
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Review

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15 pages, 2325 KiB  
Review
The Production of Complement Inhibitor Proteins in Mammalian Cell Lines—Light at the End of the Tunnel?
by Attila Szvetnik and Vilmos Tubak
Biomedicines 2024, 12(3), 646; https://doi.org/10.3390/biomedicines12030646 - 14 Mar 2024
Viewed by 1069
Abstract
Therapeutic recombinant proteins are powerful tools used for the treatment of many detrimental diseases such as diabetes, cancer, multiple sclerosis, rheumatoid arthritis, hepatitis, and many more. Their importance in disease therapy is growing over small molecule drugs because of their advantages like specificity [...] Read more.
Therapeutic recombinant proteins are powerful tools used for the treatment of many detrimental diseases such as diabetes, cancer, multiple sclerosis, rheumatoid arthritis, hepatitis, and many more. Their importance in disease therapy is growing over small molecule drugs because of their advantages like specificity and reduced side effects. However, the large-scale production of certain recombinant proteins is still challenging despite impressive advancements in biomanufacturing. The complement cascade is considered a rich source of drug targets and natural regulator proteins with great therapeutic potential. However, the versatility of such proteins has been hampered by low production rates. The recent discoveries highlighted here may bring definite improvement in the large-scale recombinant production of complement inhibitor proteins or other difficult-to-express proteins in mammalian cell lines. Full article
(This article belongs to the Special Issue Complement System as a Therapeutic Target)
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