COMPLEMENT (50%) CH-50, SERUM

Reference values Modification

Test code: 158

Menemonic code: CH50

The complement system is an essential part of the immune system (1). It consists of a set of more than 40 proteins that can be activated through 3 different pathways. The complement system plays a key role in the elimination of pathogens such as bacteria and viruses, as well as in promoting inflammatory responses and other immune functions. Its proteins work together to identify and eliminate foreign organisms or infected cells.

The complement proteins that are most commonly determined in clinical practice are C3 and C4. Total complement activity (also known as hemolytic complement activity or CH50) is determined when there is suspicion of a deficiency that cannot be defined using C3 and C4. CH50 measures the overall function of the classical complement pathway, C1-C9.

In our laboratory, CH50 activity is quantified using a liposome-based technique. The reference intervals provided by the reagent manufacturer range from 31.6 to 57.6 U/mL. These values are based on studies conducted in a Japanese population. However, geographical differences can influence the complement system and, therefore, the reference values (2). To establish a more accurate reference interval for our population, Synlab has conducted a study with an anonymized sample of 17,084 individuals in whom CH50 determination was performed in our reference laboratory.

The biological reference interval estimation was carried out following the CLSI EP28-A3C protocol using outlier exclusion and an indirect method based on repeated sampling techniques (Bootstrap). The produced reference interval is from 36.5 to 83.7 U/mL.

Additionally, the unilateral 95% reference interval was estimated, which would be the most appropriate for clinical use, given that pathological CH50 values are related to its deficiency, while values above the upper limit are generally not associated with pathology but with inflammatory processes. This unilateral reference interval (95% CI) would be > 39.8 U/mL.

These newly obtained values are consistent with the findings of a similar study on CH50 activity in a European population (3).

As a result, starting from 24/03/2025, Synlab will adopt the unilateral reference interval of > 39.8 U/mL as the discriminating value for the study of CH50 activity alterations. This update will allow for better interpretation of results and greater accuracy in the diagnosis of complement system-related disorders in our population.

References

1. Costabile M. Measuring the 50% haemolytic complement (CH50) activity of serum. J Vis Exp. 2010 Mar 29;(37):1923. doi: 10.3791/1923. PMID: 20351687; PMCID: PMC3168207
2. Delanghe JR, Speeckaert R, Speeckaert MM. Complement C3 and its polymorphism: biological and clinical consequences. Pathology 2014;46:1–10.
3. Sara Capiau, Joris R. Delanghe and Pieter M. De Kesel* Evaluation of reference intervals for classical and alternative pathway functional complement assay.