Research Topic

Current Challenges in Complement Diagnostics

About this Research Topic

The complement system is an important innate immune surveillance network that has a key role in protecting our bodies against pathogens and other threats. It is a highly complex system consisting of approximately 50 soluble and cell surface-bound proteins that interact to eliminate danger signals. These signals include factors such as invading microorganisms, necrotic cells, and immune complexes. Furthermore, complement can link innate and adaptive immune responses by regulating T cell and B cell responses. The complement system is tightly regulated to avoid uncontrolled activation. Dysregulation of the complement system has been linked to numerous diseases, both rare and common. Uncontrolled or exaggerated activation can lead to life-threatening conditions such as dysregulation of coagulation, fibrinolysis, systemic inflammation and shock, and possible failure of a variety of organs such as the eyes, kidneys, skin, brain, and vascular system.

In recent years, the complement system has gained increased interest, especially as a promising candidate for therapeutic intervention. Eculizumab, the first approved complement inhibitor, is highly effective for treating atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH). Many more drug candidates are currently evaluated in ongoing clinical trials.

Given the important role of the complement system in many diseases and its potential as a therapeutic target, accurate analysis of its components is of utmost importance for diagnosis and therapy monitoring. However, accurate determination of complement status has proven to be challenging, especially in a daily clinical setting. Concentrations of complement system proteins vary widely among different laboratories due to different protocols for pre-analytical sample handling (collection, processing, and storage). Also, laboratories do not always use the correct sample type (serum vs. plasma) for the method or assay used. Other reasons for inconsistencies are the use of different techniques (e.g., ELISA vs. nephelometry), calibrators, reagents, and antibodies. This indicates the high need for standardized methods, assays, and biomaterials to assess complement function in a robust and reliable way.

The aim of this Research Topic is to provide insights into the assessment of the complement system in diagnosis and disease monitoring, for instance, by measuring complement activation markers, detection of complement autoantibodies, complement functional assays, and quantitative evaluation of individual complement proteins. Examples of complement-mediated diseases of interest are (but not limited to) autoimmune and chronic inflammatory diseases, infection, and cancer.

We welcome Original Research, Review, Mini-Review, Hypothesis and Theory, and Opinion articles that cover, but are not limited to, the following subjects:

• Accurate assessment of complement in a diagnostic setting.
• New tools and approaches for investigating and/or assessing complement activation.
• Standardization of complement analysis.
• Identification of biomarkers adding to complement diagnostics or are predictive for disease severity and/or outcome in complement-mediated diseases.
• Pharmaceutical or technological developments focusing on next-generation complement therapeutics.

Dr. Erik J. M. Toonen is an employee of Hycult Biotech, which is involved in developing assays for the assessment of complement components. The other Topic Editors declare no other competing interests in relation to the Research Topic theme.


Keywords: complement diagnostics, complement system, assessment of complement components, diagnostic techniques and procedures, complement-mediated diseases


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

The complement system is an important innate immune surveillance network that has a key role in protecting our bodies against pathogens and other threats. It is a highly complex system consisting of approximately 50 soluble and cell surface-bound proteins that interact to eliminate danger signals. These signals include factors such as invading microorganisms, necrotic cells, and immune complexes. Furthermore, complement can link innate and adaptive immune responses by regulating T cell and B cell responses. The complement system is tightly regulated to avoid uncontrolled activation. Dysregulation of the complement system has been linked to numerous diseases, both rare and common. Uncontrolled or exaggerated activation can lead to life-threatening conditions such as dysregulation of coagulation, fibrinolysis, systemic inflammation and shock, and possible failure of a variety of organs such as the eyes, kidneys, skin, brain, and vascular system.

In recent years, the complement system has gained increased interest, especially as a promising candidate for therapeutic intervention. Eculizumab, the first approved complement inhibitor, is highly effective for treating atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH). Many more drug candidates are currently evaluated in ongoing clinical trials.

Given the important role of the complement system in many diseases and its potential as a therapeutic target, accurate analysis of its components is of utmost importance for diagnosis and therapy monitoring. However, accurate determination of complement status has proven to be challenging, especially in a daily clinical setting. Concentrations of complement system proteins vary widely among different laboratories due to different protocols for pre-analytical sample handling (collection, processing, and storage). Also, laboratories do not always use the correct sample type (serum vs. plasma) for the method or assay used. Other reasons for inconsistencies are the use of different techniques (e.g., ELISA vs. nephelometry), calibrators, reagents, and antibodies. This indicates the high need for standardized methods, assays, and biomaterials to assess complement function in a robust and reliable way.

The aim of this Research Topic is to provide insights into the assessment of the complement system in diagnosis and disease monitoring, for instance, by measuring complement activation markers, detection of complement autoantibodies, complement functional assays, and quantitative evaluation of individual complement proteins. Examples of complement-mediated diseases of interest are (but not limited to) autoimmune and chronic inflammatory diseases, infection, and cancer.

We welcome Original Research, Review, Mini-Review, Hypothesis and Theory, and Opinion articles that cover, but are not limited to, the following subjects:

• Accurate assessment of complement in a diagnostic setting.
• New tools and approaches for investigating and/or assessing complement activation.
• Standardization of complement analysis.
• Identification of biomarkers adding to complement diagnostics or are predictive for disease severity and/or outcome in complement-mediated diseases.
• Pharmaceutical or technological developments focusing on next-generation complement therapeutics.

Dr. Erik J. M. Toonen is an employee of Hycult Biotech, which is involved in developing assays for the assessment of complement components. The other Topic Editors declare no other competing interests in relation to the Research Topic theme.


Keywords: complement diagnostics, complement system, assessment of complement components, diagnostic techniques and procedures, complement-mediated diseases


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

30 November 2021 Abstract
31 January 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

30 November 2021 Abstract
31 January 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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