Startseite Immunochemical quantification of free immunoglobulin light chains from an analytical perspective
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Immunochemical quantification of free immunoglobulin light chains from an analytical perspective

  • Takanari Nakano , Shuichi Miyazaki , Hidenori Takahashi , Akira Matsumori , Taro Maruyama , Tsugikazu Komoda und Atsuo Nagata
Veröffentlicht/Copyright: 21. September 2011
Veröffentlichen auch Sie bei De Gruyter Brill
Manuskript einreichen Informationen für Autor*innen
Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 44 Heft 5

Abstract

Immunoglobulin light chains are components of antibodies, but some exist in a free form in serum and urine as a result of their excess production over heavy chains. Free light chain (FLC) levels are of the order of milligram per liter in normal serum and urine, but marked increases have been observed in various disease conditions. It has now been established that the measurement of FLC levels contributes to diagnosis and clinical management in monoclonal gammopathies. Recent developments in FLC assays have been adapted to several automated platforms and they have now become available in laboratories. There have, however, been some concerns regarding the analytical aspects. The current assay specificity appears to be insufficient to prevent the influence of intact light chains of several orders of magnitude greater than FLCs in serum. Moreover, the heterogeneous nature of light chains makes accurate quantification unreliable. FLC assays have never been standardized because of the lack of an international reference calibrator. In this review, we summarize the reports on FLC measurements and examine the specificity of anti-FLC antibodies and the reliability of FLC assays. We also discuss difficulties in the standardization and setting of normal reference intervals for FLC assays.

Keywords: antibody; Bence Jones protein; free immunoglobulin light chain; immunoassay; standardization
Disclosure of potential conflicts of interest: S. Miyazaki and A. Nagata are employees of YAMASA Corporation, which provides materials for FLC ELISAs, and they will be involved in marketing these products. T. Nakano and A. Nagata have developed FLC ELISAs at YAMASA. Corresponding author: Takanari Nakano, PhD, Department of Biochemistry, Saitama Medical School, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan Phone/Fax: +81-492-76-1155,

References

1. Bence Jones H. Papers on chemical pathology: lecture III. Lancet 1847; ii:88–92.10.1016/S0140-6736(02)86528-XSuche in Google Scholar

2. Edelman GM, Gally JA. The nature of Bence-Jones proteins. Chemical similarities to polypetide chains of myeloma globulins and normal gamma-globulins. J Exp Med 1962; 116:207–27.Suche in Google Scholar

3. Merlini G, Aguzzi F, Whicher J. Monoclonal gammopathies. J Int Fed Clin Chem 1997; 9:171–6.Suche in Google Scholar

4. Graziani M, Merlini G, Petrini C. Guidelines for the analysis of Bence Jones protein. Clin Chem Lab Med 2003; 41:338–46.10.1515/CCLM.2003.054Suche in Google Scholar

5. Marshall T, Williams KM. Electrophoretic analysis of Bence Jones proteinuria. Electrophoresis 1999; 20:1307–24.10.1002/(SICI)1522-2683(19990601)20:7<1307::AID-ELPS1307>3.0.CO;2-PSuche in Google Scholar

6. Levinson SS, Keren DF. Free light chains of immunoglobulins: clinical laboratory analysis. Clin Chem 1994; 40:1869–78.10.1093/clinchem/40.10.1869Suche in Google Scholar

7. Brigden ML, Neal ED, McNeely MD, Hoag GN. The optimum urine collections for the detection and monitoring of Bence Jones proteinuria. Am J Clin Pathol 1990; 93:689–93.10.1093/ajcp/93.5.689Suche in Google Scholar

8. Monos DS, Bina M, Kahn SN. Evaluation and optimization of variables in immunofixation electrophoresis for the detection of IgG paraproteins. Clin Biochem 1989; 22:369–71.10.1016/S0009-9120(89)80034-7Suche in Google Scholar

9. Tan M, Epstein WV. A direct immunologic assay of human sera for Bence Jones proteins (L-chains). J Lab Clin Med 1965; 66:344–56.Suche in Google Scholar

10. Sölling K, Nielsen JL, Sölling J, Ellegaard J. Free light chains of immunoglobulins in serum from patients with leukaemias and multiple myeloma. Scand J Haematol 1982; 28:309–18.10.1111/j.1600-0609.1982.tb00532.xSuche in Google Scholar

11. McLaughlin P, Alexanian R. Myeloma protein kinetics following chemotherapy. Blood 1982; 60:851–5.10.1182/blood.V60.4.851.851Suche in Google Scholar

12. Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001; 47:673–80.10.1093/clinchem/47.4.673Suche in Google Scholar

13. Bradwell AR, Carr-Smith H, Mead GP, Drayson M. Serum free light chain immunoassays and their clinical application. Clin Appl Immunol Rev 2002; 3:17–33.10.1016/S1529-1049(02)00064-8Suche in Google Scholar

14. Katzmann JA, Abraham RS, Dispenzieri A, Lust JA, Kyle RA. Diagnostic performance of quantitative κ and λ free light chain assays in clinical practice. Clin Chem 2005; 51:878–81.10.1373/clinchem.2004.046870Suche in Google Scholar

15. Gertz MA, Commenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN. Definition of organ involvement and treatment response in primary systemic amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis. In: Gateau G, Kyle RA, Skinner M, editors. Amyloid and amyloidosis. Boca Raton, FL: CRC Press, 2004:151–3.Suche in Google Scholar

16. Tate JR, Gill D, Cobcroft R, Hickman PE. Practical considerations for the measurement of free light chains in serum. Clin Chem 2003; 49:1252–7.10.1373/49.8.1252Suche in Google Scholar

17. Nakano T, Nagata A. ELISAs for free human immunoglobulin light chains in serum: improvement of assay specificity by using two specific antibodies in a sandwich detection method. J Immunol Methods 2004; 293:183–9.10.1016/j.jim.2004.08.002Suche in Google Scholar

18. Sölling K. Free light chains of immunoglobulins. Scand J Clin Lab Invest Suppl 1981; 157:1–83.Suche in Google Scholar

19. Bradwell AR. Serum free light chain measurements move to center stage. Clin Chem 2005; 51:805–7.10.1373/clinchem.2005.048017Suche in Google Scholar

20. Dammacco F, Waldenström J. Serum and urine light chain levels in benign monoclonal gammapathies, multiple myeloma and Waldenström's macroglobulinaemia. Clin Exp Immunol 1968; 3:911–21.Suche in Google Scholar

21. Mann D, Granger H, Fahey JL. Use of insoluble antibody for quantitative determination of small amounts of immunoglobulin. J Immunol 1969; 102:618–24.10.4049/jimmunol.102.3.618Suche in Google Scholar

22. Peterson PA, Berggård I. Urinary immunoglobulin components in normal, tubular, and glomerular proteinuria: quantities and characteristics of free light chains, IgG, IgA, and Fc-gamma fragment. Eur J Clin Invest 1971; 1:255–64.10.1111/eci.1971.1.4.255Suche in Google Scholar

23. Abraham GN, Waterhouse C. Evidence for defective immunoglobulin metabolism in severe renal insufficiency. Am J Med Sci 1974; 268:227–33.10.1097/00000441-197410000-00003Suche in Google Scholar

24. Sölling K. Free light chains of immunoglobulins in normal serum and urine determined by radioimmunoassay. Scand J Clin Lab Invest 1975; 35:407–12.10.3109/00365517509095760Suche in Google Scholar

25. Hemmingsen L, Skaarup P. Urinary excretion of ten plasma proteins in patients with febrile diseases. Acta Med Scand 1977; 201:359–64.10.1111/j.0954-6820.1977.tb15712.xSuche in Google Scholar

26. Cole PW, Durie BG, Salmon SE. Immunoquantitation of free light chain immunoglobulins: applications in multiple myeloma. J Immunol Methods 1978; 19:341–9.10.1016/0022-1759(78)90018-2Suche in Google Scholar

27. Robinson EL, Gowland E, Ward ID, Scarffe JH. Radioimmunoassay of free light chains of immunoglobulins in urine. Clin Chem 1982; 28:2254–8.10.1093/clinchem/28.11.2254Suche in Google Scholar

28. Ling NR, Lowe J, Hardie D, Evans S, Jefferis R. Detection of free κ chains in human serum and urine using pairs of monoclonal antibodies reacting with Ck epitopes not available on whole immunoglobulins. Clin Exp Immunol 1983; 52:234–40.Suche in Google Scholar

29. McLeod BC, Viernes AL, Sassetti RJ. Serum-free light chain analysis by crossed immunoelectrophoresis: correlation with plasmapheresis in light chain disease nephropathy. Am J Hematol 1983; 15:75–88.10.1002/ajh.2830150109Suche in Google Scholar

30. Brouwer J, Otting-van de Ruit M, Busking-van der Lely H. Estimation of free light chains of immunoglobulins by enzyme immunoassay. Clin Chim Acta 1985; 150:267–74.10.1016/0009-8981(85)90254-2Suche in Google Scholar

31. Rudick RA, Peter DR, Bidlack JM, Knutson DW. Multiple sclerosis: free light chains in cerebrospinal fluid. Neurology 1985; 35:1443–9.10.1212/WNL.35.10.1443Suche in Google Scholar

32. Teppo AM, Groop L. Urinary excretion of plasma proteins in diabetic subjects. Increased excretion of kappa light chains in diabetic patients with and without proliferative retinopathy. Diabetes 1985; 34:589–94.10.2337/diab.34.6.589Suche in Google Scholar

33. Axiak SM, Krishnamoorthy L, Guinan J, Raison RL. Quantitation of free κ light chains in serum and urine using a monoclonal antibody based inhibition enzyme-linked immunoassay. J Immunol Methods 1987; 99:141–7.10.1016/0022-1759(87)90043-3Suche in Google Scholar

34. Fagnart OC, Sindic CJ, Laterre C. Free kappa and lambda light chain levels in the cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. J Neuroimmunol 1988; 19:119–32.10.1016/0165-5728(88)90041-0Suche in Google Scholar

35. Lolli F, Amaducci L. Measurement of free kappa immunoglobulin light chains in the cerebrospinal fluid by a competitive avidin-biotin ELISA. Clin Chim Acta 1989; 182:229–34.10.1016/0009-8981(89)90081-8Suche in Google Scholar

36. Mehta PD, Cook SD, Troiano RA, Coyle PK. Increased free light chains in the urine from patients with multiple sclerosis. Neurology 1991; 41:540–4.10.1212/WNL.41.4.540Suche in Google Scholar

37. Stanescu GL, Swick AR, Tuohy VK, Rudick RA. Sensitive competitive-binding ELISAs for quantifying free kappa and lambda light chains in cerebrospinal fluid. J Clin Lab Anal 1991; 5:206–11.10.1002/jcla.1860050310Suche in Google Scholar PubMed

38. Tillyer CR, Iqbal J, Raymond J, Gore M, McIlwain TJ. Immunoturbidimetric assay for estimating free light chains of immunoglobulins in urine and serum. J Clin Pathol 1991; 44:466–71.10.1136/jcp.44.6.466Suche in Google Scholar PubMed PubMed Central

39. Wakasugi K, Sasaki M, Suzuki M, Azuma N, Nobuto T. Increased concentrations of free light chain lambda in sera from chronic hemodialysis patients. Biomater Artif Cells Immobilization Biotechnol 1991; 19:97–109.10.3109/10731199109117819Suche in Google Scholar

40. Nelson M, Brown RD, Gibson J, Joshua DE. Measurement of free kappa and lambda chains in serum and the significance of their ratio in patients with multiple myeloma. Br J Haematol 1992; 81:223–30.10.1111/j.1365-2141.1992.tb08211.xSuche in Google Scholar

41. Wakasugi K, Suzuki H, Imai A, Konishi S, Kishioka H. Immunoglobulin free light chain assay using latex agglutination. Int J Clin Lab Res 1995; 25:211–5.10.1007/BF02592700Suche in Google Scholar

42. Ohtani K, Mashiko T, Jimbo S, Ohtani H. Determination of free light chain in urine by latex immunoassay. Kitasato Med 1997; 27:33–26.Suche in Google Scholar

43. Abe M, Goto T, Kosaka M, Wolfenbarger D, Weiss DT, Solomon A. Differences in kappa to lambda (κ:λ) ratios of serum and urinary free light chains. Clin Exp Immunol 1998; 111:457–62.10.1046/j.1365-2249.1998.00487.xSuche in Google Scholar

44. Nakano T, Nagata A. ELISAs for free light chains of human immunoglobulins using monoclonal antibodies: comparison of their specificity with available polyclonal antibodies. J Immunol Methods 2003; 275:9–17.10.1016/S0022-1759(02)00512-4Suche in Google Scholar

45. Epstein WV, Tan M. Increase of L-chain proteins in the sera of patients with systemic lupus erythematosus and the synovial fluids of patients with peripheral rheumatoid arthritis. Arthritis Rheum 1966; 9:713–9.10.1002/art.1780090508Suche in Google Scholar

46. Cooper A, Bluestone R. Free immunoglobulin light chains in connective tissue diseases. Ann Rheum Dis 1968; 27:537–43.10.1136/ard.27.6.537Suche in Google Scholar

47. Le Bricon T, Bengoufa D, Benlakehal M, Bousquet B, Erlich D. Urinary free light chain analysis by the Freelite immunoassay: a preliminary study in multiple myeloma. Clin Biochem 2002; 35:565–7.10.1016/S0009-9120(02)00386-7Suche in Google Scholar

48. Levinson SS. Studies of Bence Jones proteins by immunonephelometry. Ann Clin Lab Sci 1992; 22:100–9.Suche in Google Scholar

49. Boege F, Koehler B, Liebermann F. Identification and quantification of Bence-Jones proteinuria by automated nephelometric screening. J Clin Chem Clin Biochem 1990; 28:37–42.Suche in Google Scholar

50. Nakano T, Nagata A, Takahashi H. Ratio of urinary free immunoglobulin light chain κ to λ in the diagnosis of Bence Jones proteinuria. Clin Chem Lab Med 2004; 42:429–34.10.1515/CCLM.2004.075Suche in Google Scholar PubMed

51. Boux HA, Raison RL, Walker KZ, Hayden GE, Basten A. A tumor-associated antigen specific for human kappa myeloma cells. J Exp Med 1983; 158:1769–74.10.1084/jem.158.5.1769Suche in Google Scholar PubMed PubMed Central

52. Abe M, Goto T, Kennel SJ, Wolfenbarger D, Macy SD, Weiss DT, et al. Production and immunodiagnostic applications of antihuman light chain monoclonal antibodies. Am J Clin Pathol 1993; 100:67–74.10.1093/ajcp/100.1.67Suche in Google Scholar

53. Jenkins MA, O'Leary TD, Guerin MD. Identification and quantitation of human urine proteins by capillary electrophoresis. J Chromatogr B Biomed Appl 1994; 662:108–12.10.1016/0378-4347(94)00387-4Suche in Google Scholar

54. Katzmann JA, Clark R, Sanders E, Landers JP, Kyle RA. Prospective study of serum protein capillary zone electrophoresis and immunotyping of monoclonal proteins by immunosubtraction. Am J Clin Pathol 1998; 110:503–9.10.1093/ajcp/110.4.503Suche in Google Scholar

55. Bradwell AR, Carr-Smith HD, Mead GP, Harvey TC, Drayson MT. Serum test for assessment of patients with Bence Jones myeloma. Lancet 2003; 361:489–91.10.1016/S0140-6736(03)12457-9Suche in Google Scholar

56. Mead GP, Carr-Smith HD, Drayson MT, Bradwell AR. Detection of Bence Jones myeloma and monitoring of myeloma chemotherapy using immunoassays specific for free immunoglobulin light chains. Clin Lab 2003; 49:25–7.Suche in Google Scholar

57. Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001; 97:2900–2.10.1182/blood.V97.9.2900Suche in Google Scholar PubMed

58. Graziani MS, Merlini G. Measurement of free light chains in urine. Clin Chem 2001; 47:2069–70.10.1093/clinchem/47.11.2069Suche in Google Scholar

59. Heino J, Rajamaki A, Irjala K. Turbidimetric measurement of Bence-Jones proteins using antibodies against free light chains of immunoglobulins. An artifact caused by different polymeric forms of light chains. Scand J Clin Lab Invest 1984; 44:173–6.10.3109/00365518409161401Suche in Google Scholar PubMed

60. Sölling K. Polymeric forms of free light chains in serum from normal individuals and from patients with renal diseases. Scand J Clin Lab Invest 1976; 36:447–52.10.3109/00365517609054462Suche in Google Scholar PubMed

61. Nakano T, Miyazaki S, Shinoda Y, Inoue I, Katayama S, Komoda T, et al. A proposed reference material for human free immunoglobulin light chain measurement. J Immunoassay Immunochem. In press.Suche in Google Scholar

62. Carr-Smith H, Edwards J, Showell P, Drew R, Tang LX, Bradwell AR. Preparation of an immunoglobulin free light-chain reference material. Clin Chem 2000; 46:A180.Suche in Google Scholar

63. Kyle RA. Sequence of testing for monoclonal gammopathies. Arch Pathol Lab Med 1999; 123:114–8.10.5858/1999-123-0114-SOTFMGSuche in Google Scholar PubMed

64. Keren DF, Alexanian R, Goeken JA, Gorevic PD, Kyle RA, Tomar RH. Guidelines for clinical and laboratory evaluation patients with monoclonal gammopathies. Arch Pathol Lab Med 1999; 123:106–7.10.5858/1999-123-0106-GFCALESuche in Google Scholar PubMed

65. Bush D, Keren DF. Over- and underestimation of monoclonal gammopathies by quantification of κ- and λ-containing immunoglobulins in serum. Clin Chem 1992; 38:315–6.10.1093/clinchem/38.2.315Suche in Google Scholar

66. Riches PG, Sheldon J, Smith AM, Hobbs JR. Overestimation of monoclonal immunoglobulin by immunochemical methods. Ann Clin Biochem 1991; 28:253–9.10.1177/000456329102800310Suche in Google Scholar PubMed

67. Smith AM, Thompson RA. Paraprotein estimation: a comparison of immunochemical and densitometric techniques. J Clin Pathol 1978; 31:1156–60.10.1136/jcp.31.12.1156Suche in Google Scholar PubMed PubMed Central

68. Hemmingsen L, Skaarup P. The 24-h excretion of plasma proteins in the urine of apparently healthy subjects. Scand J Clin Lab Invest 1975; 35:347–53.10.3109/00365517509095751Suche in Google Scholar

69. Groop L, Makipernaa A, Stenman S, DeFronzo RA, Teppo AM. Urinary excretion of kappa light chains in patients with diabetes mellitus. Kidney Int 1990; 37:1120–5.10.1038/ki.1990.94Suche in Google Scholar PubMed

70. Ohtani S, Ohtani H. Clinical significance of free light chain in urine by latex agglutination immunoassay. Kitasato Med 1998; 28:435–45.Suche in Google Scholar

71. Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, et al. Serum reference intervals and diagnostic ranges for free κ and free λ immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 2002; 48:1437–44.10.1093/clinchem/48.9.1437Suche in Google Scholar

72. Sölling K. Normal values for free light chains in serum different age groups. Scand J Clin Lab Invest 1977; 37:21–5.10.3109/00365517709108798Suche in Google Scholar

73. Waldmann TA, Strober W, Mogielnicki RP. The renal handling of low molecular weight proteins. II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia. J Clin Invest 1972; 51:2162–74.10.1172/JCI107023Suche in Google Scholar PubMed PubMed Central

Received: 2006-1-14
Accepted: 2006-3-15
Published Online: 2011-9-21
Published in Print: 2006-5-1

©2006 by Walter de Gruyter Berlin New York

Artikel in diesem Heft

  1. CCLM: Expanding the science worldwide
  2. Factor V Leiden, prothrombin G20210A substitution and hormone therapy: indications for molecular screening
  3. Immunochemical quantification of free immunoglobulin light chains from an analytical perspective
  4. De novo deletion removes a conserved motif in the C-terminus of ABCA4 and results in cone-rod dystrophy
  5. Molecular detection of squamous cell carcinoma antigen transcripts in peripheral blood of cancer patients
  6. Influence of human haptoglobin polymorphism on oxidative stress induced by free hemoglobin on red blood cells
  7. Real-time RT-PCR quantification of PRAME gene expression for monitoring minimal residual disease in acute myeloblastic leukaemia
  8. Association of high-sensitive C-reactive protein with advanced stage β-cell dysfunction and insulin resistance in patients with type 2 diabetes mellitus
  9. A longitudinal evaluation of urinary glycosaminoglycan excretion in normoalbuminuric type 1 diabetic patients
  10. National survey on the execution of the oral glucose tolerance test (OGTT) in a representative cohort of Italian laboratories
  11. The reduction of cholesteryl linoleate in lipoproteins: an index of clinical severity in β-thalassemia/Hb E
  12. Alterations in serum glycosaminoglycan profiles in Graves' patients
  13. Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients
  14. Sandwich ELISAs for soluble immunoglobulin superfamily receptor translocation-associated 2 (IRTA2)/FcRH5 (CD307) proteins in human sera
  15. Utilizing ultrafiltration to remove alkaline phosphatase from clinical analyzer water
  16. Measurement of serum monoclonal components: comparison between densitometry and capillary zone electrophoresis
  17. Salivary aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase: possible markers in periodontal diseases?
  18. Reticulocyte count, mean reticulocyte volume, immature reticulocyte fraction, and mean sphered cell volume in elite athletes: reference values and comparison with the general population
  19. Serum homocysteine levels and paraoxonase 1 activity in preschool aged children in Greece
  20. The effects of adrenocorticotrophic hormone and cortisol on homocysteine and vitamin B concentrations
  21. Plasma, salivary and urinary cotinine in non-smoker Italian women exposed and unexposed to environmental tobacco smoking (SEASD study)
  22. Cut-off values for total serum immunoglobulin E between non-atopic and atopic children in north-west Croatia
  23. Thyroglobulin assay during thyroxine treatment in low-risk differentiated thyroid cancer management: comparison with recombinant human thyrotropin-stimulated assay and imaging procedures
  24. Evaluation of serum levels of p53 in hepatocellular carcinoma in Egypt
  25. Insufficient filling of vacuum tubes as a cause of microhemolysis and elevated serum lactate dehydrogenase levels. Use of a data-mining technique in evaluation of questionable laboratory test results
  26. Evaluation of three different specimen types (serum, plasma lithium heparin and serum gel separator) for analysis of certain analytes: clinical significance of differences in results and efficiency in use
  27. Comparative evaluation of a new immunoradiometric assay for corticotropin
  28. Mast cells in atherosclerosis as a source of the cytokine RANKL
  29. Falsely increased total serum protein due to dextran interference
https://doi.org/10.1515/CCLM.2006.118
Schlagwörter für diesen Artikel
antibody; Bence Jones protein; free immunoglobulin light chain; immunoassay; standardization

Artikel in diesem Heft

  1. CCLM: Expanding the science worldwide
  2. Factor V Leiden, prothrombin G20210A substitution and hormone therapy: indications for molecular screening
  3. Immunochemical quantification of free immunoglobulin light chains from an analytical perspective
  4. De novo deletion removes a conserved motif in the C-terminus of ABCA4 and results in cone-rod dystrophy
  5. Molecular detection of squamous cell carcinoma antigen transcripts in peripheral blood of cancer patients
  6. Influence of human haptoglobin polymorphism on oxidative stress induced by free hemoglobin on red blood cells
  7. Real-time RT-PCR quantification of PRAME gene expression for monitoring minimal residual disease in acute myeloblastic leukaemia
  8. Association of high-sensitive C-reactive protein with advanced stage β-cell dysfunction and insulin resistance in patients with type 2 diabetes mellitus
  9. A longitudinal evaluation of urinary glycosaminoglycan excretion in normoalbuminuric type 1 diabetic patients
  10. National survey on the execution of the oral glucose tolerance test (OGTT) in a representative cohort of Italian laboratories
  11. The reduction of cholesteryl linoleate in lipoproteins: an index of clinical severity in β-thalassemia/Hb E
  12. Alterations in serum glycosaminoglycan profiles in Graves' patients
  13. Alterations in anti-oxidative defence enzymes in erythrocytes from sporadic amyotrophic lateral sclerosis (SALS) and familial ALS patients
  14. Sandwich ELISAs for soluble immunoglobulin superfamily receptor translocation-associated 2 (IRTA2)/FcRH5 (CD307) proteins in human sera
  15. Utilizing ultrafiltration to remove alkaline phosphatase from clinical analyzer water
  16. Measurement of serum monoclonal components: comparison between densitometry and capillary zone electrophoresis
  17. Salivary aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase: possible markers in periodontal diseases?
  18. Reticulocyte count, mean reticulocyte volume, immature reticulocyte fraction, and mean sphered cell volume in elite athletes: reference values and comparison with the general population
  19. Serum homocysteine levels and paraoxonase 1 activity in preschool aged children in Greece
  20. The effects of adrenocorticotrophic hormone and cortisol on homocysteine and vitamin B concentrations
  21. Plasma, salivary and urinary cotinine in non-smoker Italian women exposed and unexposed to environmental tobacco smoking (SEASD study)
  22. Cut-off values for total serum immunoglobulin E between non-atopic and atopic children in north-west Croatia
  23. Thyroglobulin assay during thyroxine treatment in low-risk differentiated thyroid cancer management: comparison with recombinant human thyrotropin-stimulated assay and imaging procedures
  24. Evaluation of serum levels of p53 in hepatocellular carcinoma in Egypt
  25. Insufficient filling of vacuum tubes as a cause of microhemolysis and elevated serum lactate dehydrogenase levels. Use of a data-mining technique in evaluation of questionable laboratory test results
  26. Evaluation of three different specimen types (serum, plasma lithium heparin and serum gel separator) for analysis of certain analytes: clinical significance of differences in results and efficiency in use
  27. Comparative evaluation of a new immunoradiometric assay for corticotropin
  28. Mast cells in atherosclerosis as a source of the cytokine RANKL
  29. Falsely increased total serum protein due to dextran interference
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 7.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/CCLM.2006.118/html
Button zum nach oben scrollen