Skip to main content
Journal of Clinical Laboratory Analysis logoLink to Journal of Clinical Laboratory Analysis
. 2001 Mar 13;14(6):265–270. doi: 10.1002/1098-2825(20001212)14:6<265::AID-JCLA3>3.0.CO;2-A

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

Robert F Ritchie 1,, Glenn E Palomaki 1, Louis M Neveux 1, Olga Navolotskaia 1
PMCID: PMC6807951  PMID: 11138607

Abstract

Limiting bedside use of positive acute phase protein measurements (α1‐acid glycoprotein (orosomucoid), α1‐antitrypsin, and haptoglobin) has been the lack of satisfactory methods for quantifying serum levels and a credible reference material. 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. Sixty publications reporting reference intervals have been identified which meet the criteria used in our prior two studies, and these have been analyzed statistically. Previous small studies of these individual proteins agree on average, over their constrained age ranges, with our life‐long reference ranges. This meta‐analysis provides support for our reference ranges and places them in the perspective of previous publications. J. Clin. Lab. Anal. 14:265–270, 2000. © 2000 Wiley‐Liss, Inc.

Keywords: serum proteins, acute phase proteins, 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. 1998. Reference distributions for immunoglobulins A, G, and M: a comparison of a large cohort to the world’s literature. J Lab Clin Anal 12:371–377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O. 1999. 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 13:280–286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Whicher JT, Ritchie RF, Johnson AM, Baudner S, Bienvenu J, Blirup‐Jensen S. 1994. New international reference preparation for proteins in human serum (RPPHS). Clin Chem 40:934–938. [PubMed] [Google Scholar]
  • 4. Song CS, Merkatz IR, Rifkind AB, Gillette PN, Kappas A. 1970. The influence of pregnancy and oral contraceptive steroids on the concentration of plasma proteins. Am J Obstet Gynecol 108:227–231. [DOI] [PubMed] [Google Scholar]
  • 5. Lyngbye J, Krøll J. 1971. Quantitative immunoelectrophoresis of proteins in serum from a normal population: season‐, age‐, and sex‐related variations. Clin Chem 17:495–500. [PubMed] [Google Scholar]
  • 6. Dotchev D, Liappis N, Hungerland H. 1973. Sex‐specific differences of serum proteins in adults and influence of oral hormonal contraceptives on serum protein compositions. Clin Chim Acta 44:431–435. [DOI] [PubMed] [Google Scholar]
  • 7. Lou K, Bowers J. 1975. Electoimmunoquantitation of serum protein cross‐linked by glutaraldehyde. J Immunol Methods 9:69–79. [DOI] [PubMed] [Google Scholar]
  • 8. Ihrig J, Schwartz HJ, Rynbrandt DJ, Kleinerman J. 1975. Serum trypsin inhibitory capacity and Pi phenotypes. II. Prevalence of α1‐antitrypsin deficiency in an allergy population. Am J Clin Pathol 64:297–303. [DOI] [PubMed] [Google Scholar]
  • 9. Rees ED, Hollingsworth JW, Hoffman TR, Black H, Hearn TL. 1975. Smoking and disease. Effect on serum antitrypsin in hospitalized patients. Arch Environ Health 30:402–408. [DOI] [PubMed] [Google Scholar]
  • 10. Olsen GN, Harris JO, Castle JR, Waldman RH, Karmgard HJ. 1975. α1‐Antitrypsin content in the serum, alveolar macrophages, and alveolar lavage fluid of smoking and nonsmoking normal subjects. J Clin Invest 55:427–430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Barnett TB, Gottovi D, Johnson AM. 1975. Protease inhibitors in chronic obstructive pulmonary disease. Am Rev Resp Dis 111:587–593. [DOI] [PubMed] [Google Scholar]
  • 12. Alk?aersig N, Fletcher A, Burstein R. 1975. Association between oral contraceptive use and thromboembolism: a new approach to its investigation based on plasma fibrinogen chromatography. Am J Obstet Gynecol 122:199–211. [DOI] [PubMed] [Google Scholar]
  • 13. Statland BE, Winkel P, Killingsworth LM. 1976. Factors contributing to intra‐individual variation of serum constituents: 6. Physiological day‐to‐day variation in concentrations of 10 specific proteins in sera of healthy subjects. Clin Chem 22:1635–1638. [PubMed] [Google Scholar]
  • 14. Winkel P, Statland BE, Nielsen MK. 1976. Biologic and analytic components of variation of concentration values of selected proteins. Scand J Clin Lab Invest 36:531–537. [DOI] [PubMed] [Google Scholar]
  • 15. Nyulassy S, Hnilica P, Buc M, Guman M, Hirschová V, Stefanovi J. 1977. Subacute (de Quervain’s) thyroiditis: association with HLA‐Bw 35 antigen and abnormalities of the complement system, immunoglobulins and other serum proteins. J Clin Endocrinol Metab 45:270–274. [DOI] [PubMed] [Google Scholar]
  • 16. Ritchie RF. 1979. Serum protein profile analysis and interpretation: some basis information Immunoassays in the clinical laboratory. New York: Alan R. Liss, Inc. p 227–242. [Google Scholar]
  • 17. Freer DE, Statland BE, Johnson M, Felton H. 1979. Reference values for selected enzyme activities and protein concentrations in serum and plasma derived from cord‐blood specimens. Clin Chem 25:565–569. [PubMed] [Google Scholar]
  • 18. Baskies AM, Chretien PB, Yang C, et al. 1979. Serum glycoproteins and immunoglobulins in nasopharyngeal carcinoma. Am J Surg 138:478–488. [DOI] [PubMed] [Google Scholar]
  • 19. Bienvenu J, Sann L, Bienvenu F, et al. 1981. Laser nephelometry of orosomucoid in serum of newborns: reference intervals and relation to bacterial infections. Clin Chem 27:721–726. [PubMed] [Google Scholar]
  • 20. Pongpaew P, Schelp FP. 1983. Albumin, prealbumin, transferrin, and serum proteinase inhibitors in asymptomatic and hospitalized Thai alcohol drinkers. J Stud Alcohol 44:381–383. [DOI] [PubMed] [Google Scholar]
  • 21. Behr W, Schlimok G, Firchau V, Paul HA. 1985. 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 23:157–166. [DOI] [PubMed] [Google Scholar]
  • 22. Ward AM, White PAE, Wild G. 1985. Reference ranges for serum α1‐antitrypsin. Arch Dis Child 60:261–262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Bienvenu J, Bienvenu F, Sann L. 1986. Acute phase proteins in the neonate: normal values and clinical interest in disease. Protides Biol Fluids 34:573–579. [Google Scholar]
  • 24. Dati F, Stienen L. 1987. Reference values for nine plasma proteins in healthy subjects of various ages using nephelometric technique. 39th National Meeting of the American Association for Clinical Chemistry, San Francisco, CA, July 19–24, 1987. Washington, DC: American Association for Clinical Chemistry; 1987, Abstract.
  • 25. Lockitch G, Halstead AC, Quigley G, MacCallum C. 1988. Age‐ and sex‐specific pediatric reference intervals: study design and methods illustrated by measurement of serum proteins with the Behring LN Nephelometer. Clin Chem 34:1618–1621. [PubMed] [Google Scholar]
  • 26. El‐Kassimi FA, Warsy AS, Uz‐Zaman A, Pillai DK. 1989. α1‐Antitrypsin serum levels in widespread bronchiectasis. Resp Med 83:119–121. [DOI] [PubMed] [Google Scholar]
  • 27. Mackiewicz A, Khan MA, Reynolds TL, Van der Linden S, Kushner I. 1989. Serum IgA, acute phase proteins, and glycosylation of α1‐acid glycoprotein in ankylosing spondylitis. Ann Rheum Dis 48:99–103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Poole AR, Witter J, Roberts N, et al. 1990. Inflammation and cartilage metabolism in rheumatoid arthritis. Arthritis Rheum 33:790–799. [DOI] [PubMed] [Google Scholar]
  • 29. Raubenstine DA, Ballantine TVN, Greecher CP, Webb SL. 1990. Neonatal serum protein levels as indicators of nutritional status: normal values and correlation with anthropometric data. J Pediatr Gastroenterol Nutr 10:53–61. [DOI] [PubMed] [Google Scholar]
  • 30. Veering BTH, Burm AGL, Souverijn JHM, Serree JMP, Spierdijk J. 1990. The effect of age on serum concentrations of albumin and α1‐acid glycoprotein. Br J Clin Pharmacol 29:201–206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Pressac M, Vignoli L, Aymard P, Ingenbleek Y. 1990. Usefulness of a prognostic inflammatory and nutritional index in pediatric clinical practice. Clin Chim Acta 188:129–136. [DOI] [PubMed] [Google Scholar]
  • 32. Kawerk N, Succari‐Aderschlag M, Foglietti M‐J. 1991. Microheterogeneity of α1‐acid glycoprotein in healthy elderly subjects: patterns obtained by crossed affino‐immunoelectrophoresis. Clin Chim Acta 202:65–72. [DOI] [PubMed] [Google Scholar]
  • 33. Healy D, Calvin J, Whitehouse AM, et al. 1991. α1‐Acid glycoprotein in major depressive and eating disorders. J Affect Disord 22:13–20. [DOI] [PubMed] [Google Scholar]
  • 34. Feely J, Grimm T. 1991. A comparison of drug protein binding and α1‐acid glycoprotein concentration in Chinese and Caucasians. Br J Clin Pharmacol 31:551–552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. Winslet MC, Sherwell J, Radley S, Keighley MRB. 1991. The acute phase protein response in Crohn’s colitis. Biochem Soc Trans 19:222S. [DOI] [PubMed] [Google Scholar]
  • 36. Malvy DJ‐M, Provéda J‐D, Debruyne M, et al. 1992. Laser immunonephelometry reference intervals for eight serum proteins in healthy children. Clin Chem 38:394–399. [PubMed] [Google Scholar]
  • 37. Tietz NW, Shuey DF, Wekstein DR. 1992. Laboratory values in fit aging individuals: sexagenarians through centenarians. Clin Chem 38:1167–1185. [PubMed] [Google Scholar]
  • 38. Sveger T, Ohlsson K, Svenningsen N. 1992. Neonatal plasma concentrations of secretory leukocyte protease inhibitor. Acta Paediatr 81:270–271. [DOI] [PubMed] [Google Scholar]
  • 39. Neely AN, Warden GD, Rieman M, Friedberg DL, Holder IA. 1992. Components of the increased circulating proteolytic activity in pediatric burn patients. J Trauma 33:807–812. [DOI] [PubMed] [Google Scholar]
  • 40. Finotti P, Piccoli A, Carraro P. 1992. Alteration of plasma proteinase–antiproteinase system in type 1 diabetic patients. Influence of sex and relationship with metabolic control. Diabetes Res Clin Pract 18:35–42. [DOI] [PubMed] [Google Scholar]
  • 41. Maes M, Scharpé S, Van Grootel L, et al. 1992. Higher α1‐antitrypsin, haptoglobin, ceruloplasmin, and lower retinol‐binding protein plasma levels during depression: further evidence for the existence of an inflammatory response during that illness. J Affective Disord 24:183–192. [DOI] [PubMed] [Google Scholar]
  • 42. Krecicki T, Leluk M. 1992. Acute phase reactant proteins: an aid to monitoring surgical treatment of laryngeal carcinoma. J Laryngol Otol 106:613–615. [DOI] [PubMed] [Google Scholar]
  • 43. Singhal A, Doherty JF, Raynes JG, et al. 1993. Is there an acute‐phase response in steady‐state sickle cell disease? Lancet 341:651–653. [DOI] [PubMed] [Google Scholar]
  • 44. Clark GH, Fraser CG. 1993. Biological variation of acute phase proteins. Ann Clin Biochem 30:373–376. [DOI] [PubMed] [Google Scholar]
  • 45. Ray D, Krishna KS. 1993. α1‐Antitrypsin in tropical pulmonary eosinophilia. Chest 104:487–492. [DOI] [PubMed] [Google Scholar]
  • 46. Berni I, Contantini A, Di Vano M. 1993. Monoclonal gammopathies in Alzheimer disease. Clin Chem 39:166. [PubMed] [Google Scholar]
  • 47. Daher R, Van Lente F. 1994. Concanavalin A‐bound selenoprotein in human serum analyzed by graphite furnace atomic absorption spectrometry. Clin Chem 40:62–70. [PubMed] [Google Scholar]
  • 48. Kuvibidila S, Warrier RP, Yu L, Ode D, Mbele V. 1994. Reference levels of acute phase reactant proteins in healthy Zairean women in the reproductive age group. J Trop Med Hyg 97:239–243. [PubMed] [Google Scholar]
  • 49. Vaziri ND, Gonzales EC, Shayestehfar B, Barton CH. 1994. Plasma levels and urinary excretion of fibrinolytic and protease inhibitory proteins in nephrotic syndrome. J Lab Clin Med 124:118–124. [PubMed] [Google Scholar]
  • 50. Viljoen M, Roux LJ, Pretorius JP, Coetzee IH, Viljoen E. 1995. Hemostatic competency and elastase– α1‐proteinase inhibitor levels in surgery, trauma, and sepsis. J Trauma 39:381–385. [DOI] [PubMed] [Google Scholar]
  • 51. Kanakoudi F, Drossou V, Tzimouli V, et al. 1995. Serum concentrations of 10 acute‐phase proteins in healthy term and preterm infants from birth to age 6 months. Clin Chem 41:605–608. [PubMed] [Google Scholar]
  • 52. Varela AS, López Sáez JJB. 1995. Utility of plasmatic levels of α1‐antiprotease (A1AP) as a cancer marker. Cancer Lett 89:15–21. [DOI] [PubMed] [Google Scholar]
  • 53. Baker CJ, Fiore A, Connolly ES, Baker KZ, Solomon RA. 1995. Serum elastase and α1‐antitrypsin levels in patients with ruptured and unruptured cerebral aneurysms. Neurosurgery 37:56–61. [DOI] [PubMed] [Google Scholar]
  • 54. Katnik I, Jadach J, Kmieciak K, Gerber J, Dobryszycka W. 1995. Measurement of haptoglobin by the reaction with concanavalin A in sera of patients with ovarian tumors. Eur J Clin Chem Clin Biochem 33:727–732. [DOI] [PubMed] [Google Scholar]
  • 55. Hosseine SJ, Farid R, Ghalighi MR, Feely J. 1995. Interethnic differences in drug protein binding and α1‐acid glycoprotein concentration. Ir J Med Sci 164:26–27. [DOI] [PubMed] [Google Scholar]
  • 56. Shahid A, Siddiqui AA, Aziz S, Ansari M, Zuberi SJ, Waqar MAA. 1996. Serum α1‐antitrypsin and pulmonary emphysema. J Pak Med Assoc 46:102–103. [PubMed] [Google Scholar]
  • 57. Ballou SP, Lozanski GB, Hodder S, et al. 1996. Quantitative and qualitative alterations of acute‐phase proteins in healthy elderly persons. Age Aging 25:224–230. [DOI] [PubMed] [Google Scholar]
  • 58. David O, Fiorucci GC, Tosi MT, et al. 1996. Hematological studies in children with Down syndrome. Pediatr Hematol Oncol 13:271–275. [DOI] [PubMed] [Google Scholar]
  • 59. Sluóewska A, Rybakowski JK, Sobieska M, Wiktorowicz K. 1996. Concentration and microheterogeneity glycophorms of α1‐acid glycoprotein in major depressive disorder. J Affective Disord 39:149–155. [DOI] [PubMed] [Google Scholar]
  • 60. Held C, Hjemdahl P, Rehnqvist N, et al. 1997. Haemostatic markers, inflammatory parameters and lipids in male and female patients in the Angina Prognosis Study in Stockholm (APSIS). A comparison with healthy controls. J Intern Med 241:59–69. [DOI] [PubMed] [Google Scholar]
  • 61. Lacki JK, Leszczynski P, Kelemen J, Müller W, Mackiewicz SH. 1997. Cytokine concentration in serum of lupus erythematous patients: the effect on acute‐phase response. J Med 28:99–107. [PubMed] [Google Scholar]
  • 62. Cederholm T, Arner P, Palmblad J. 1997. Low circulating leptin levels in protein‐energy malnourished chronically ill elderly patients. J Internal Medicine 242:377–382. [DOI] [PubMed] [Google Scholar]
  • 63. Shahid A, Zuberi SJ, Siddiqui AA, Waqar MA. 1997. Genetic markers and duodenal ulcer. J Pak Med Assoc 47:135–137. [PubMed] [Google Scholar]
  • 64. Dati F, Schumann G, Thomas L, et al. 1996. Consensus of a group of professional societies and diagnostic companies on guidelines for the interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/CAP reference material (CRM 470). Eur J Clin Chem Biochem 34:517–520. [PubMed] [Google Scholar]
  • 65. Itoh Y, Ichihara K, Kanno T, et al. 1997. Serum protein standardization project in Japan: evaluation of an IFCC reference material (RPPHS/CRM470) and establishment of reference intervals. J Clin Lab Anal 11:39–44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66. Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY. 1998. Reference distributions for immunoglobulins A, G and M: a practical, simple and clinically relevant approach in a large cohort. J Clin Lab Anal 12:363–370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67. Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY. 1999. Reference distributions for the negative acute phase proteins, albumin, transferrin, and transthyretin: a practical, simple and clinically relevant approach in a large cohort. J Lab Clin Anal 13:280–286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68. National Committee for Clinical Laboratory Standards . 1995. How to Define and Determine Reference Intervals in the Clinical Laboratory: Approved Guideline. NCCLS Document C28‐A. 771 East Lancaster Avenue, Villanova, PA 19085:NCCLS.
  • 69. Whicher JW. 1997. 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, 1997, Viareggio, Italy. New York: W. de Gruyter.

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

RESOURCES