Reference distributions for alpha2-macroglobulin: a practical, simple and clinically relevant approach in a large...

Area of Science:

• Clinical Chemistry
• Biomarkers
• Human Physiology

Background:

• Establishing accurate reference values for serum proteins is crucial for clinical diagnosis.
• Alpha-2-macroglobulin (alpha(2)M) is a key protease inhibitor with complex regulatory factors.
• Previous studies have indicated potential influences on alpha(2)M levels, necessitating further investigation.

Purpose of the Study:

• To determine reference values for serum alpha(2)-macroglobulin (alpha(2)M) in a large, well-defined Caucasian population.
• To assess the influence of age, gender, and specific medical conditions on alpha(2)M levels.
• To validate the use of normalized data for simplified interpretation of alpha(2)M measurements.

Main Methods:

• Analysis of serum samples from 40,420 Caucasian individuals tested between 1994 and 2000.
• Standardization of measurements against Certified Reference Material (CRM 470)/Reference Preparation for Proteins in Human Serum (RPPHS).
• Statistical analysis including exclusion/inclusion of individuals with elevated C-reactive protein to assess acute phase response.

Main Results:

• Serum alpha(2)M levels do not respond to acute phase drive in humans.
• Nephrotic syndrome, diabetes mellitus, and chronic liver disease significantly affect alpha(2)M levels.
• Distinct age- and gender-dependent patterns were observed, with males higher from birth to age 12 and females thereafter until the ninth decade.

Conclusions:

• The study provides robust reference values for serum alpha(2)M.
• Age and gender are significant determinants of alpha(2)M levels, independent of acute inflammation.
• Normalized data distributions facilitate simplified interpretation of individual alpha(2)M measurements.