1887

Abstract

Leprosy, a spectral disease manifested on the basis of host immune responses,is complicated by its reactional stages, namely type I reversal reaction (RR)and type II erythema nodosum leprosum (ENL). These reactional stagesare characterized by uncontrolled and aberrant immune responses. Biomarkersfor reactional stages would aid in early diagnosis, efficient treatment, preventionof neurological complications and prediction of predisposition to reactionalstages. In this study, comparative analysis of the serum proteome of leprosypatients by two-dimensional electrophoresis (2DE) followed by massspectrometry showed differential expression of acute-phase protein -acid glycoprotein (AGP; also known as orosomucoid).AGP levels in untreated ENL cases were significantly higher than in lepromatousleprosy (LL; a non-reactional disease stage) (=0.0126),RR (=0.0176) and healthy controls (=0.0030).These data were confirmed using ELISA. The levels of AGP decreased to normallevels after treatment with multidrug therapy and thalidomide (=0.0167). In a follow-up study, AGP levels, which were highin the untreated ENL stage, decreased significantly at 5 days (=0.0084) and 21 days (=0.0027)post-treatment. A stage-dependent increase in AGP in an LL patient who progressedinto the ENL stage was also shown. Glycosylation analysis by 2DE showed differentialexpression of acidic glycoforms of AGP in untreated ENL cases. Changes inAGP concentration and differential expression of isoforms correlated withthe inflammatory condition in ENL and also with the treatment regimen. Thus,initial validation of AGP as an ENL-specific biomarker and treatment indicatorwas shown in this study.

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2010-04-01
2024-03-28
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References

  1. Barnes P. F., Chatterjee D., Brennan P. J., Rea T. H., Modlin R. L. 1992; Tumor necrosis factor productionin patients with leprosy. Infect Immun 60:1441–1446
    [Google Scholar]
  2. Boutten A., Dehoux M., Deschenes M., Rouzeau J. D., Bories P. N., Durand G. 1992; α 1-Acid glycoprotein potentiates lipopolysaccharide-induced secretionof interleukin-1 β , interleukin-6 and tumor necrosis factor- α by human monocytes and alveolar and peritoneal macrophages. Eur J Immunol 22:2687–2695 [CrossRef]
    [Google Scholar]
  3. Bradford M. M. 1976; A rapid andsensitive method for the quantitation of microgram quantities of protein utilizingthe principle of protein-dye binding. Anal Biochem 72:248–254 [CrossRef]
    [Google Scholar]
  4. Bührer-Sékula S., Sarno E. N., Oskam L., Koop S., Wichers I., Nery J. A., Vieira L. M., de Matos H. J., Faber W. R. &other authors; 2000; Use of ML dipstick as a toolto classify leprosy patients. Int J Lepr Other Mycobact Dis 68:456–463
    [Google Scholar]
  5. Bührer-Sékula S., Smits H. L., Gussenhoven G.C., van Leeuwen J., Amador S., Fujiwara T., Klatser P. R., Oskam L. 2003; Simple and fast lateral flow test for classificationof leprosy patients and identification of contacts with high risk of developingleprosy. J Clin Microbiol 41:1991–1995 [CrossRef]
    [Google Scholar]
  6. Candiano G., Bruschi M., Musante L., Santucci L., Ghiggeri G. M., Carnemolla B., Orecchia P., Zardi L., Righetti P. G. 2004; Blue silver: a very sensitive colloidal CoomassieG-250 staining for proteome analysis. Electrophoresis 25:1327–1333 [CrossRef]
    [Google Scholar]
  7. Ceciliani F., Pocacqua V. 2007; The acute phase protein α 1-acid glycoprotein: a model for altered glycosylation during diseases. Curr ProteinPept Sci 8:91–108
    [Google Scholar]
  8. De Graaf T. W., Van der Stelt M. E., Anbergen M. G., van Dijk W. 1993; Inflammation-induced expressionof sialyl Lewis X-containing glycan structures on α 1-acidglycoprotein (orosomucoid) in human sera. J Exp Med 177:657–666 [CrossRef]
    [Google Scholar]
  9. Faber W. R., Iyer A. M., Fajardo T. T., Dekker T., Villahermosa L. G., Abalos R. M., Das P. K. 2004; Serialmeasurement of serum cytokines, cytokine receptors and neopterin in leprosypatients with reversal reactions. Lepr Rev 75:274–281
    [Google Scholar]
  10. Fassbender K, Fassbender M, Schaberg T, Sobieska M, Muller W. 1995; Glycosylation of α 1-acid glycoprotein in bacterial lung infections: distinct pattern intuberculosis. Clin Chem 41:472–473
    [Google Scholar]
  11. Fournier T., Medjoubi N. N., Porquet D. 2000; α 1-Acid glycoprotein. Biochim Biophys Acta 1482:157–171 [CrossRef]
    [Google Scholar]
  12. Gilberts E. C., Greenstein A. J., Katsel P, Harpaz N, Greenstein R. J. 1994; Molecular evidence for twoforms of Crohn disease. Proc Natl Acad Sci U S A 91:12721–12724 [CrossRef]
    [Google Scholar]
  13. Girdhar B. K., Girdhar A., Chakma J. K. 2007; Advances in the treatment of reactions in leprosy. Indian J Lepr 79:121–134
    [Google Scholar]
  14. Gupta N., Shankernarayan N. P., Dharmalingam K. 2007; Serum proteome of leprosy patients undergoing erythemanodosum leprosum reaction: regulation of expression of the isoforms of haptoglobin. J Proteome Res 6:3669–3679 [CrossRef]
    [Google Scholar]
  15. Hamerlinck F. F., Klatser P. R., Walsh D. S., Bos J. D., Walsh G. P., Faber W. R. 1999; Serum neopterinas a marker for reactional states in leprosy. FEMS Immunol MedMicrobiol 24:405–409
    [Google Scholar]
  16. Hochepied T., Berger F. G., Baumann H., Libert C. 2003; α 1-Acid glycoprotein: anacute phase protein with inflammatory and immunomodulating properties. Cytokine Growth Factor Rev 14:25–34 [CrossRef]
    [Google Scholar]
  17. Irmak S., Tilki D., Heukeshoven J., Oliveira-Ferrer L., Friedrich M., Huland H., Ergun S. (2005).Stage-dependent increase of orosomucoid and zinc- α 2-glycoproteinin urinary bladder cancer. Proteomics 5:4296–4304 [CrossRef]
    [Google Scholar]
  18. Iyer A., Hatta M., Usman R., Luiten S., Oskam L., Faber W., Geluk A., Das P. 2007; Serum levels ofinterferon- γ , tumour necrosis factor- α , solubleinterleukin-6R and soluble cell activation markers for monitoring responseto treatment of leprosy reactions. Clin Exp Immunol 150:210–216 [CrossRef]
    [Google Scholar]
  19. Iyer A., van Eijk M., Silva E., Hatta M., Faber W., Aerts J. M., Das P. K. 2009; Increased chitotriosidaseactivity in serum of leprosy patients: association with bacillary leprosy. Clin Immunol 131:501–509 [CrossRef]
    [Google Scholar]
  20. Izumi S., Fujiwara T., Ikeda M., Nishimura Y., Sugiyama K., Kawatsu K. 1990; Novel gelatin particleagglutination test for serodiagnosis of leprosy in the field. J Clin Microbiol 28:525–529
    [Google Scholar]
  21. Jain S, Rajput A, Kumar Y, Uppuluri N, Arvind A. S., Tatu U. 2005; Proteomic analysis of urinary proteinmarkers for accurate prediction of diabetic kidney disorder. JAssoc Physicians India 53:513–520
    [Google Scholar]
  22. Johnson D. A., Smith K. D. 2006; The efficacy of certain anti-tuberculosis drugs is affected by bindingto α -1-acid glycoprotein. Biomed Chromatogr 20:551–560 [CrossRef]
    [Google Scholar]
  23. Johnson A. M., Hyltoft Petersen P., Whicher J. T., Carlstrom A., MacLennan S. 2004; Reference intervalsfor serum proteins: similarities and differences between adult Caucasian andAsian Indian males in Yorkshire, UK. Clin Chem Lab Med 42:792–799
    [Google Scholar]
  24. Kahawita I. P., Lockwood D. N. 2008; Towards understanding the pathology of erythema nodosum leprosum. Trans R Soc Trop Med Hyg 102:329–337 [CrossRef]
    [Google Scholar]
  25. Kleinert P., Kuster T., Arnold D., Jaeken J., Heizmann C. W., Troxler H. 2007; Effect of glycosylationon the protein pattern in 2-D-gel electrophoresis. Proteomics 7:15–22 [CrossRef]
    [Google Scholar]
  26. Kupcova V., Turecky L., Detkova Z., Prikazska M., Keleova A. 2003; Changes in acute phase proteins after anti-tumornecrosis factor antibody (infliximab) treatment in patients withCrohn's disease. Physiol Res 52:89–93
    [Google Scholar]
  27. Lacunza I., Kremmer T., Diez-Masa J. C., Sanz J., deFrutos M. 2007; Comparison of α -1-acidglycoprotein isoforms from healthy and cancer patients by capillary IEF. Electrophoresis 28:4447–4451 [CrossRef]
    [Google Scholar]
  28. Lockwood D. N. 2002; Leprosy elimination –a virtual phenomenon or a reality?. BMJ 324:1516–1518 [CrossRef]
    [Google Scholar]
  29. Martínez Cordero E., González M. M., Aguilar L. D., Orozco E. H., Hernández Pando R. 2008; Alpha-1-acid glycoprotein, its local production and immunopathologicalparticipation in experimental pulmonary tuberculosis. Tuberculosis (Edinb 88:203–211 [CrossRef]
    [Google Scholar]
  30. Misra N., Murtaza A., Walker B., Narayan N. P., Misra R.S., Ramesh V., Singh S., Colston M. J., Nath I. 1995; Cytokine profile of circulating T cells of leprosy patientsreflects both indiscriminate and polarized T-helper subsets: T-helper phenotypeis stable and uninfluenced by related antigens of Mycobacterium leprae . Immunology 86:97–103
    [Google Scholar]
  31. Monot M., Honore N., Garnier T., Araoz R., Coppee J. Y., Lacroix C., Sow S., Spencer J. S., Truman R. W. other authors 2005; On the origin of leprosy. Science 308:1040–1042 [CrossRef]
    [Google Scholar]
  32. Mortz E., Krogh T. N., Vorum H., Gorg A. 2001; Improved silver staining protocols for high sensitivityprotein identification using matrix-assisted laser desorption/ionization-timeof flight analysis. Proteomics 1:1359–1363 [CrossRef]
    [Google Scholar]
  33. Nigam P. K., Srivastava P., Patra P. K. 2005; Serum adenosine deaminase levels in reactional and non-reactionalleprosy. Indian J Dermatol Venereol Leprol 71:20–22 [CrossRef]
    [Google Scholar]
  34. Oskam L., Slim E., Buhrer-Sekula S. 2003; Serology: recent developments, strengths, limitations and prospects: a state of the art overview. Lepr Rev 74:196–205
    [Google Scholar]
  35. Parkash O. M., Girdhar B. K., Sengupta U. 1993; Serum lactoferrin in lepromatous leprosy patients. Lepr Rev 64:295–301
    [Google Scholar]
  36. Richardus J. H., Habbema J. D. 2007; The impact of leprosy control on the transmission of M. leprae : is elimination being attained?. Lepr Rev 78:330–337
    [Google Scholar]
  37. Ridley D. S. 1988 Pathogenesisof Leprosy and Related Diseases London: Wright;
    [Google Scholar]
  38. Ridley D. S., Jopling W. H. 1966; Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis 34:255–273
    [Google Scholar]
  39. Saha K., Bhatnagar A., Sharma V. K., Chakrabarty A.K. 1985; Enzyme immunoassay of serum β -2-microglobulinlevels in various histological forms of leprosy with special reference toits elevation in type I and type II lepra reactions. J Clin Microbiol 21:658–661
    [Google Scholar]
  40. Salgame P., Abrams J. S., Clayberger C., Goldstein H., Convit J., Modlin R. L., Bloom B. R. 1991; Differinglymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science 254:279–282 [CrossRef]
    [Google Scholar]
  41. Silva E. A., Iyer A., Ura S., Lauris J. R., Naafs B., Das P. K., Vilani-Moreno F. 2007; Utility of measuringserum levels of anti-PGL-I antibody, neopterin and C-reactive protein in monitoringleprosy patients during multi-drug treatment and reactions. TropMed Int Health 12:1450–1458
    [Google Scholar]
  42. Silva Miranda M., Rodríguez K. W., MartínezCordero E., Rojas-Espinosa O. 2006; Expressionof cyclooxygenase-2, α 1-acid-glycoprotein and induciblenitric oxide synthase in the developing lesions of murine leprosy. Int J Exp Pathol 87:485–494 [CrossRef]
    [Google Scholar]
  43. Steger J. W., Barrett T. L. 1994 Military Dermatology, Part III: Disease and the Environment .Washington DC: Office of the Surgeon General at TMM Publications; BordenInstitute:
    [Google Scholar]
  44. Su S. J., Yang B. C., Wang Y. S., Yeh T. M. 1999; α 1-Acid glycoprotein-inducedtumor necrosis factor- α secretion of human monocytes is enhancedby serum binding proteins and depends on protein tyrosine kinase activation. Immunopharmacology 41:21–29 [CrossRef]
    [Google Scholar]
  45. Theophilus S. 1980; Treatment withthalidomide in steroid dependency and neuritis. Lepr India 52:423–428
    [Google Scholar]
  46. Turk B. E., Jiang H., Liu J. O. 1996; Binding of thalidomide to α 1-acid glycoproteinmay be involved in its inhibition of tumor necrosis factor α production. Proc Natl Acad Sci U S A 93:7552–7556 [CrossRef]
    [Google Scholar]
  47. Van Dijk W., Brinkman-Van der Linden E. C. M., Havenaar E. C. 1998; Glycosylation of α 1-acid glycoprotein (orosomucoid) in health and disease: occurrence,regulation and possible functional implications. Trends GlycosciGlycotechnol 10:235–245
    [Google Scholar]
  48. Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L. 1991; Definingprotective responses to pathogens: cytokine profiles in leprosy lesions. Science 254:277–279 [CrossRef]
    [Google Scholar]
  49. Young D. B., Buchanan T. M. 1983; A serological test for leprosy with a glycolipid specific for Mycobacteriumleprae . Science 221:1057–1059 [CrossRef]
    [Google Scholar]
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