Reference distributions for the positive acute phase serum proteins, alpha(1)-acid glycoprotein (orosomucoid), alpha(1)-antitrypsin, and haptoglobin:A practical, simple, and clinically relevant approach in a large cohort

Most clinical conditions are accompanied by corresponding changes in serum levels of some, if not all, of the acute phase proteins. While conditions t hat affect the acute phase proteins are usually inflammatory in nature, non -inflammatory conditions also can cause changes (e.g., malnutrition, some m alignancies without secondary inflammation, and genetic polymorphism). Only after the confounding effects of non-inflammatory conditions are taken int o account can these measurements be used to detect and stage the inflammato ry process and to evaluate the impact of treatment. In this third article i n a series, reference ranges for serum levels for three of the acute phase proteins that increase during inflammation are examined: alpha (1)-acid gly coprotein (orosomucoid), alpha (1)-antitrypsin, and haptoglobin. The study is based on a cohort of 55,199 Caucasian individuals from northern New Engl and, tested in our laboratory between 1994 and 1999. Measurements were stan dardized against CRM 470 (RPPHS) and analyzed using a previously described statistical approach. individuals with unequivocal laboratory evidence of i nflammation (C-reactive protein of 10 mg/l or higher) were excluded. Levels of alpha (1)-acid glycoprotein changed little during life and between the sexes. Levels of alpha (1)-antitrypsin varied somewhat by age, rising sligh tly beyond age 55; males followed a pattern similar to that for females. Fo r this protein, it was necessary to apply two equations to describe the low er levels associated with certain phenotypes. Haptoglobin levels fell signi ficantly during the first decade of life for both males and females and cli mbed thereafter. Males and females displayed a similar pattern. When values were expressed as multiples of the age- and gender-specific median revels, the resulting distributions fitted a log-Gaussian distribution well over a broad range. When patient data are normalized in this manner, the distribu tion parameters can be used to assign a centile corresponding to an individ ual's measurement, thus simplifying interpretation. J. Clin. Lab. Anal. 14: 284-292, 2000. (C) 2000 Wiley-Liss, Inc.