Skip to main content
PMC home page
Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2004 Mar 29;18(2):148–152. doi: 10.1002/jcla.20013

Reference distributions for α2‐macroglobulin: A comparison of a large cohort to the world's literature

Robert F Ritchie 1,✉, Glenn E Palomaki 1, Louis M Neveux 1, Olga Navolotskaia 1
PMCID: PMC6807940  PMID: 15065216

Abstract

The lack of satisfactory methods for quantifying serum levels and a credible reference material has limited bedside use of serum alpha2‐macroglobulin (α2M) measurements. Great strides have been made in the last few years. The remaining barrier to more relevant and cost effective use of serum protein data for diagnosis and prognosis is the availability of reliable reference intervals from birth to old age for both males and females. A total of 40 publications reporting reference intervals have been identified that meet the criteria used in our prior five studies, and these have been analyzed statistically. On average, previous small studies of these individual proteins agree with our life‐long reference ranges over their constrained age ranges. This meta‐analysis provides support for our reference ranges and places them in the perspective of previous publications. J. Clin. Lab. Anal. 18:148–152, 2004. © 2004 Wiley‐Liss, Inc.

Keywords: serum proteins, alpha2‐macroglobulin, meta‐analysis, CRM 470/RPPHS

Contributor Information

Robert F. Ritchie, Email: ritchie@fbr.org.

Glenn E. Palomaki, Email: palomaki@fbr.org

REFERENCES

  • 1. Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O. Reference distributions for immunoglobulins A, G, and M: a comparison of a large cohort to the world's literature. J Lab Clin Anal 1998;12:371–377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O. Reference distributions for the negative acute phase proteins, albumin, transferrin and transthyretin: a comparison of a large cohort to the world's literature. J Lab Clin Anal 1999;13:280–286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O. Reference distributions for the positive acute phase proteins, α1‐acid glycoprotein (orosomucoid), α1‐antitrypsin and haptoglobin: a comparison of a large cohort to the world's literature. Lab Clin Anal 2000;14:265–270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O. Reference distributions for serum iron, total iron binding capacity and transferrin saturation: a comparison of a large cohort to the world's literature. J Lab Clin Anal 2002;16:246–252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. Ritchie RF, Palomaki GE, Navolotskaia O, Neveux LM, Ledue TB, Craig WY. Reference distributions for serum C3 and C4: a comparison of a single large cohort of reference values to the worlds literature. J Clin Lab Anal 18:139–147.15065215 [Google Scholar]
  • 6. Whicher JT, Ritchie RF, Johnson AM, Baudner S, Bienvenu J, Blirup‐Jensen S. New international reference preparation for proteins in human serum (RPPHS). Clin Chem 1994;40:934–938. [PubMed] [Google Scholar]
  • 7. Weiss WA. Normal values of specific serum proteins in children and adults. Klin Wochschr 1965;43:273. [DOI] [PubMed] [Google Scholar]
  • 8. James K, Taylor FB, Fudenberg HH. Trypsin stabilizers in human serum. The role of alpha‐2‐macroglobulin. Clin Chim Acta 1966;13:359–368. [DOI] [PubMed] [Google Scholar]
  • 9. Wilding P, Adham NF, Mehl JW, Haverback BJ. Alpha‐2‐macroglobulin concentrations in human serum. Nature 1967;214:1226–1227. [DOI] [PubMed] [Google Scholar]
  • 10. Cleve H, Alexander K, Mitzkat HJ, Nissen P, Salzmann I. Serum glycoproteins in diabetes mellitus; quantitative immunological determination of acid alpha 1‐glycoprotein, Gc, alpha 2‐macroglobulin and hemopexin in diabetics with and without angiopathy. Diabetologia 1968;4:48–55. [DOI] [PubMed] [Google Scholar]
  • 11. Gault MH, Elzer E, Gabe A. Prediction of haptoglobin and α2‐macroglobulin concentrations from electrophoretic patterns of serum α2‐globulin. Clin Chem 1970;16:925–930. [PubMed] [Google Scholar]
  • 12. Song CS, Merkatz IR, Rifkind AB, Gillette PN, Kappas A. The influence of pregnancy and oral contraceptive steroids on the concentration of plasma proteins. Am J Obstet Gynecol 1970;106:227–231. [DOI] [PubMed] [Google Scholar]
  • 13. Mendenhall HW. Serum protein concentrations in pregnancy. Am J Obstet Gynecol 1970;106:388–399. [DOI] [PubMed] [Google Scholar]
  • 14. Laurell C‐B, Jeppsson J‐O. Protease inhibitors in plasma In: Putnam F, editor. The plasma proteins. Structure, function and genetic control. Volume 1 New York: Academic Press; 1975. p 229–264. [Google Scholar]
  • 15. Lyngbye J, Krøll J. Quantitative immunoelectrophoresis of proteins in serum from a normal population: season‐, age‐, and sex‐related variations. Clin Chem 1971;17:495–500. [PubMed] [Google Scholar]
  • 16. Weeke B, Krasilnikoff PA. The concentration of 21 serum proteins in normal children and adults. Acta Med Scand 1972;192:149–155. [DOI] [PubMed] [Google Scholar]
  • 17. Dotchev D, Liappis N, Hungerland H. Sex‐specific differences of serum proteins in adults and influence of oral hormonal contraceptives on serum protein composition. Clin Chem Acta 1973;44:431–435. [DOI] [PubMed] [Google Scholar]
  • 18. Agostoni A, Marasini B, Stabilini R, Del Ninno E, Pontello M. Multivariate analysis of serum protein assays in chronic hepatitis and postnecrotic cirrhosis. Clin Chem 1974;20:428–429. [PubMed] [Google Scholar]
  • 19. Brackertz D, Hagmann J, Keuppers F. Proteinase inhibitors in rheumatoid arthritis. Ann Rheum Dis 1975;34:225–230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. McBean LD, Smith JC Jr, Berne BH, Halsted JA. Serum zinc and alpha2‐macroglobulin concentration in myocardial infarction, decubitus ulcer, multiple myeloma, prostatic carcinoma, Downv's syndrome and nephrotic syndrome. Clin Chim Acta 1974;50:43–51. [DOI] [PubMed] [Google Scholar]
  • 21. Barnett TB, Gottove D, Johnson AM. Protease inhibitors in chronic obstructive pulmonary disease. Am Rev Resp Dis 1975;111:587–593. [DOI] [PubMed] [Google Scholar]
  • 22. Svartman M, Potter EV, Poon‐King T, Earle DP. Immunoglobulins and complement components in synovial fluid of patients with acute rheumatic fever. J Clin Invest 1975;56:111–117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Hendrik M, Doeglas G, Bleumink E. Protease inhibitors in plasma of patients with chronic urticaria. Arch Dermatol 1975;111:979–985. [PubMed] [Google Scholar]
  • 24. Alkjaersig N, Fletcher A, Burstein R. Association between oral contraceptive use and thromboembolism: a new approach to its investigation based on plasma fibrinogen chromatography. Am J Obstet Gynecol 1975;122:199–211. [DOI] [PubMed] [Google Scholar]
  • 25. Snyder S, Durham BC, Iskandrian AS, Coodley EL, Linhart JW. Serum lipids and glycoproteins in acute myocardial infarction. Am Heart J 1975;90:582–586. [DOI] [PubMed] [Google Scholar]
  • 26. Norberg R, Birke G, Hedfors E, Plantin L‐O. Metabolism of α2‐macroglobulin: regulation and distribution In: Rothchild M, Waldman T, editors. Plasma protein metabolism. Regulation of synthesis, distribution, and degradation. New York: Academic Press; 1970. p 427–436. [Google Scholar]
  • 27. Statland BE, Winkel P, Killingsworth LM. Factors contributing to intra‐individual day‐to‐day variation in concentrations of 10 specific proteins in sera of healthy subjects. Clin Chem 1976;22:1635–1638. [PubMed] [Google Scholar]
  • 28. Nyulassy S, Hnilica P, Buc M, Guman M, Hirschová V, Štefanovič J. Subacute (de Quervain's) thyroiditis: association with HLA‐Bw35 antigen and abnormalities of the complement system, immunoglobulins and other serum proteins. J Clin Endocrinol Metab 1977;45:270–274. [DOI] [PubMed] [Google Scholar]
  • 29. Pozzilli P, Tamburrano G, Mercalli ME, Javicoli M. Raised alpha‐2‐macroglobulin levels in acromegaly. Horm Metab Res 1978;10:359. [DOI] [PubMed] [Google Scholar]
  • 30. Ritchie RF. Serum protein profile analysis and interpretation: some basic information. Immunoassays in the clinical laboratory. New York: AR Liss, Inc., 1979; p 227–242. [Google Scholar]
  • 31. Freer DE, Statland BE, Johnson M, Felton H. Reference values for selected enzyme activities and protein concentrations is serum and plasma derived from cord‐blood specimens. Clin Chem 1979;25:565–569. [PubMed] [Google Scholar]
  • 32. James K, Merriman J, Gray RS, Duncan LJ, Herd R. Serum alpha 2‐macroglobulin in diabetes. J Clin Pathol 1980;33:163–166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Pongpaew P, Schelp FP. Albumin, prealbumin, transferrin and serum proteinase inhibitors in asymptomatic and hospitalized Thai alcohol drinkers. J Stud Alcohol 1983;44:381–383. [DOI] [PubMed] [Google Scholar]
  • 34. Behr W, Schlimok G, Firchau V, Paul HA. Determination of reference intervals for 10 serum proteins measured by rate nephelometry, taking into consideration different sample groups and different distribution functions. J Clin Chem Clin Biochem 1985;23:157–166. [DOI] [PubMed] [Google Scholar]
  • 35. Ahlsten G, Tuvemo T, Gebre‐Medhin M. Selected trace elements and proteins in serum of apparently healthy newborn infants of mothers who smoked during pregnancy. Acta Paediatr Scand 1989;78:671–676. [DOI] [PubMed] [Google Scholar]
  • 36. Gaillard MC, von Arb M, da Costa A, Kilroe‐Smith TA. Functional and immunological concentrations of α2‐macroglobulin compared in plasma of subjects without α1‐protease inhibitor deficiency. Clin Chem 1989;35:1535–1537. [PubMed] [Google Scholar]
  • 37. Raubenstine DA, Ballantine TVN, Greecher CP, Webb SL. Neonatal serum protein levels as indicators of nutritional status: normal values and correlation with anthropometric data. J Pediatr Gastroenterol Nutr 1990;10:53–61. [DOI] [PubMed] [Google Scholar]
  • 38. Winslet MC, Sherwell J, Radley S, Keighley MRB. The acute phase protein response in Crohn's colitis. Biochem Soc Trans 1991;19:222S. [DOI] [PubMed] [Google Scholar]
  • 39. Sveger T, Ohlsson K, Svenningsen N. Neonatal plasma concentrations of secretory leucocyte protease inhibitor. Acta Pæditr 1992;81:270–271. [DOI] [PubMed] [Google Scholar]
  • 40. Finotti P, Piccoli A, Varraro P. Alteration of plasma proteinase‐antiproteinase system in type 1 diabetic patients. Influence of sex and relationships with metabolic control. Diabetes Res Clin Prac 1992;18:35–42. [DOI] [PubMed] [Google Scholar]
  • 41. Mohácsi A, Fülöp T Jr, Kozlovsky B, Hauck M, Kiss I, Leövey A. Sera and leukocyte elastase‐type protease and antiprotease activity in healthy and atherosclerotic subjects of various ages. J Gerontol 1992;47:B154–B158. [DOI] [PubMed] [Google Scholar]
  • 42. Cliver SP, Goldenberg RL, Neel NR, Tamura T, Johnston KE, Hoffman HJ. Neonatal cord serum alpha 2‐macroglobulin and fetal size at birth. Early Hum Dev 1993;33:201–206. [DOI] [PubMed] [Google Scholar]
  • 43. Vaziri ND, Gonzales EC, Shayestehfar B, Barton CH. Plasma levels and urinary excretion of fibrinolytic and protease inhibitory proteins in nephrotic syndrome. J Lab Clin Med 1994;124:118–124. [PubMed] [Google Scholar]
  • 44. Kanakoudi F, Drossou V, Tzimouli V, et al. Serum concentrations of 10 acute‐phase proteins in healthy term and preterm infants from birth to age 6 months. Clin Chem 1995;41:605–608. [PubMed] [Google Scholar]
  • 45. Shiota G, Umeki K, Okano J‐I, Kawasaki H. Hepatocyte growth factor and acute phase proteins in patients with chronic liver disease. J Med 1995;26:295–308. [PubMed] [Google Scholar]
  • 46. de Sain‐van der Velden MG, Rabelink TJ, Reijngoud DJ, et al. Plasma alpha 2 macroglobulin is increased in nephrotic patients as a result of increased synthesis alone. Kidney Int 1998;54:530–535. [DOI] [PubMed] [Google Scholar]
  • 47. Ritchie RF, Palomaki GE, Navolotskaia O, Neveux LM, Ledue TB, Craig WY. Reference distributions for alpha2‐macroglobulin: a practical, simple and clinically relevant approach in a large cohort. J Lab Clin Anal (in press). [DOI] [PMC free article] [PubMed]
  • 48. National Committee for Clinical Laboratory Standards . How to define and determine reference intervals in the clinical laboratory: approved guideline. NCCLS Document C28‐A. NCCLS: Villanova, PA; 1995. [Google Scholar]
  • 47. Whicher, JW . Minutes of the International Federation of Clinical Chemistry meeting of the Committee on Plasma Proteins, Scientific Division, August 20, 1997, Basel, Switzerland and October 8, Viareggio, Italy, 1997.

Articles from Journal of Clinical Laboratory Analysis are provided here courtesy of Wiley

RESOURCES