THE COMMITTEE FOR THE STANDARDIZATION AND QUALITY ASSESSMENT OF COMPLEMENT MEASUREMENTS
By Professor Michael Kirschfink, Heidelberg University
The complement system comprises over 30 soluble and membrane-bound proteins within a fine-tuned network which plays a fundamental role in the immune system (Figure 1). As expected, laboratory analysis of the complement system comprises over 30 soluble and membrane-bound proteins within a fine-tuned network which plays a fundamental role in the immune system (Figure 1). As expected, laboratory analysis of the complement system serves in the diagnosis and monitoring of a broad array of pathological contexts. The challenge of analyzing such a complex system is assisted by stepwise guided approaches (Figure 2). The lability of several complement components represents an additional challenge to clinical and research laboratories analyzing the complement system.
The committee for Standardization and Quality Assessment of Complement Measurements was founded in 2008 during the International Complement Workshop in Basel, Switzerland and is dedicated to standardization and harmonization of the diagnostic complement tests among the laboratories. The committee is affiliated with the International Complement Society (ICS) and the IUIS. During two strategic workshops in Budapest (2009, 2016), the latter with 31 participants representing 21 complement laboratories, the group defined steps for improvement focusing on developing recommendations for the most appropriate methods, calibration strategies, and how to interpret and report results of the annual external quality assessments (EQA).
Since 2010, the committee has organized regular quality assessment rounds for complement assays in collaboration with INSTAND e.V. Düsseldorf, Germany, a non-profit, interdisciplinary scientific medical society for the promotion of quality assurance in medical laboratories. In the past ten years, the number of clinical laboratories participating in these assessments has grown from 12 in 2010 to 180 in October 2019. The results of the assessments have been collected, analyzed and presented during International Complement Meetings as well as on several editions of the European and the International Immunology Congresses (Figure 3). Recent activities of the complement standardization committee have also been reported on the 17th Congress of the International Union of Immunological Societies (IUIS) in a well-attended symposium entitled “Laboratory Testing in Immunology: Recent Advances and Quality Assessment/Standardization” in Beijing, China (10/2019).
Compelling evidence accumulated in the past ten years has indicated that there is a high degree of inter-laboratory variation in the methods used, normal reference ranges and reported results. Since the European Complement Meeting in Madrid, in September 2019, the committee has been taking active steps to further standardize complement assays by defining four workgroups dedicated to functional assays, complement factors, complement activation biomarkers and autoantibodies, respectively. Special attention is given to the development of “golden” quantification standards which will be produced via dedicated protocols within certified facilities and made available to the complement laboratories.
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