Abstract
Complement not only plays a key role in host microbial defense but also modulates the adaptive immune response through modification of T- and B-cell reactivity. Moreover, a normally functioning complement system participates in hematopoiesis, reproduction, lipid metabolism, and tissue regeneration. Because of its powerful inflammatory potential, multiple regulatory proteins are needed to prevent potential tissue damage. In clinical practice, dysregulation and overactivation of the complement system are major causes of a variety of inflammatory and autoimmune diseases ranging from nephropathies, age-related macular degeneration (AMD), and systemic lupus erythematosus (SLE) to graft rejection, sepsis, and multi-organ failure. The clinical importance is reflected by the recent development of multiple drugs targeting complement with a broad spectrum of indications. The recognition of the role of complement in diverse diseases and the advent of complement therapeutics has increased the number of laboratories and suppliers entering the field. This has highlighted the need for reliable complement testing. The relatively rapid expansion in complement testing has presented challenges for a previously niche field. This is exemplified by the issue of cross-reactivity of complement-directed antibodies and by the challenges of the poor stability of many of the complement analytes. The complex nature of complement testing and increasing clinical demand has been met in the last decade by efforts to improve the standardization among laboratories. Initiated by the IUIS/ICS Committee for the Standardization and Quality Assessment in Complement Measurements 14 rounds of external quality assessment since 2010 resulted in improvements in the consistency of testing across participating institutions, while extending the global reach of the efforts to more than 200 laboratories in 30 countries. Worldwide trends of assay availability, usage, and analytical performance are summarized based on the past years’ experiences. Progress in complement analysis has been facilitated by the quality assessment and standardization efforts that now allow complement testing to provide a comprehensive insight into deficiencies and the activation state of the system. This in turn enables clinicians to better define disease severity, evolution, and response to therapy.
Highlights
The complement system is of substantial relevance for the destruction of invading microorganisms and for immune complex elimination [for review, see [1, 2]]
In 2016, members of the Quality Assurance and Standardization of Complement Measurements group hold a 2-day meeting in Budapest where a joint decision to step to the level with organizational matters was reached
It must be noted that among the 20 assays evaluated in the complement external quality assurance (EQA) program only C1 inhibitor (C1-INH) protein, C3 and C4 are parameters where the majority of the participants use the same method that is calibrated with international serum protein calibrators regularly used for various serum protein assays on the nephelometers
Summary
The complement system is of substantial relevance for the destruction of invading microorganisms and for immune complex elimination [for review, see [1, 2]]. There is increasing evidence that properdin, known as the only positive regulator of the alternative pathway, directly binds to pathogens and apoptotic cells, allowing the generation of C3 convertase on the target surface [16, 17] with subsequent opsonization, i.e. covalent binding of C3b and iC3b. These include the following: [1] assessment of the level of the basic components, [2] measurement of the levels and/or functions of the fluid phase control proteins, [3] measures of complement functions, [4] testing for complement directed autoantibodies, and [5] assessment of the fragments and complexes formed during activation. The benefit of measuring the components is Frontiers in Immunology | www.frontiersin.org
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