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Clinical usefulness of serological measurements obtained by antigen 60 in mycobacterial infections: Development of a new concept

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Summary

The humoral immune response occuring during mycobacterial infections was analysed with an ELISA test based on antigen 60. With tuberculosis, IgM antibodies indicate a primo-infection or a process of reactivation while IgG determinations allow an evaluation of the intensity of the infectious process. The test is also applicable to extrapulmonary tuberculosis, provided its sensitivity be adapted to these particular cases. This is particularly clear for tuberculous meningitis.

The test is not species-specific and allows the detection of antibodies in atypical mycobacterioses and in leprosy patients. The final differentiation must be done by clinical examinations and cultures. In leprosy patients, IgM antibodies are detected nearly as frequently as IgG antibodies. In HIV-seropositive patients, the A60 seropositivity is correlated with a reactivation of former tuberculous infections and with primary tuberculous infections. At the AIDS stage, the A-60 seropositivity is due to atypical mycobacteria, with a better IgM than IgG response.

Healthy people are negative in serology:the positive cases observed are due to inapparent infections gained by contact with an infectious focus. The seropositive cases observed in non-tuberculous hospitalized patients are restricted to some disease types, essentially lung infections (cystic fibrosis, cancer pneumopathies, sarcoidosis).

Some patients have low levels of antibodies. This anergy may be traced to the formation of immune complexes or else to a weak avidity of the specific antibodies produced.

This test should not be considered to be a diagnostic tool by itself. It should be used in conjunction with other diagnostic means that, together, allow the determination of a diagnosis.

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Abbreviations

IgG:

Immunoglobulin G

IgM:

Immunoglobulin M

A60:

Mycobacterial antigen 60

HIV:

Human Immunodeficiency Virus

AIDS:

Acquired Immunodeficiency Syndrome

ELISA:

Enzyme Linked Immunosorbent Assay

CSL:

Cerebro-spinal Liquid

References

  1. Abou-Zeid C, Harboe M, Sundsten B, Cocito C (1985) Cross-reactivity of antigens from the cytoplasm and cellwalls of some corynebacteria and mycobacteria. J Inf Dis 151:170–178

    Google Scholar 

  2. Bach MA, Wallach D, Flageul B, Hoffenbach A, Cottenot F (1986) Antibodies to phenolic glycolipid-I and the wholeMycobacterium leprae in leprosy patients:evolution during therapy. Int J Lepr 54:256–267

    Google Scholar 

  3. Baelden MC, Vanderelst B, Dieng M, Prignot J, Cocito C (1990) Serological analysis of human tuberculosis by an ELISA immunoassay with mycobacterial antigen-60. Scand J Inf Dis 22:63–73

    Google Scholar 

  4. Bardana Jr EJ, McClatchy J, Farr R, Minden P (1973) Universal occurence of antibodies to tubercle bacilli in sera from non tuberculous and tuberculous individuals. Clin Exp Immunol 13:65–77

    Google Scholar 

  5. Benjamin RG, Daniel TM (1982) Serodiagnosis of tuberculosis using the elisa of antibody to mycobacterium tuberculosis antigen 5. Am Rev Respir Dis 126:1013–1016

    Google Scholar 

  6. Beschin A, Brijs L, De Baetselier P, Cocito C (1991) Mycobacterial proliferation in macrophages is prevented by incubation with lymphocytes activated in vitro with a mycobacterial antigen complex. Europ J Immunol 21:793–797

    Google Scholar 

  7. Brett SJ, Draper P, Payne S, Rees RJ (1983) Serological activity of a characteristic phenolic glycolipid from M. leprae in sera from patients with leprosy and tuberculosis. Clin Exp Immunol 52:271–279

    Google Scholar 

  8. Casal M, Linares MJ (1988) Diagnostico serologico de la tuberculosis. Rev Esp Microbiol Clin 3:491–492

    Google Scholar 

  9. Charpin D, Herbault M, Gevaudan MJ, Saadjian M, De Micco Ph, Arnaud A, Vervloet D, Charpin J (1990) Value of ELISA using A60 antigen in the diagnosis of active pulmorary tuberculosis. Am Rev Respir Dis 142:380–384

    Google Scholar 

  10. Chatterjee BR (1990) Correspondence. Controlled clinical trials:comments on the contribution of Pr. Grosset. Int J Leprosy 58:376–378

    Google Scholar 

  11. Cho SN, Brennan SJ, Yoshimura HH, Korelitz BI, Graham DY (1986) Mycobacterial aetiology of Crohn's disease:serologic study using common mycobacterial antigens and a specific glycolipid antigen fromMycobacterium tuberculosis. Gut 27:1353–1356

    Google Scholar 

  12. Cisse MF, Agius G, Dindinaud G, Vaillant V, Hane AA, Castel O, Grollier G, Castets M (1990) Evaluation d'un ELISA utilisant l' antigène A60 de M. bovis BCG IgG et IgM spécifiques au cours d'infections mycobactériennes. Ann Biol Clin 48:369–372

    Google Scholar 

  13. Closs O, Harboe M, Axelsen NH, Bunch K, Magnusson M (1980) The antigens of mycobacterium bovis, strain BCG, studied by Crossed Immunoelectrophoresis:a Reference System. Scand J Immunol 12:249–263

    Google Scholar 

  14. Cocito C, Baelden MC, Benoit CH (1987) Immunological properties of Antigen 60 of BCG. Scand J Immunol 25:579–585

    Google Scholar 

  15. Cocito C, Vanlinden F (1986) Preparation and properties of antigen 60 from Mycobacterium bovis. Clin Exp Immunol 66:262–268

    Google Scholar 

  16. Collins FM (1988) Mycobacterium avium complex infections and development of the acquired immunodeficiency syndrome:casual opportunist or causal co-factor? Int J Leprosy 56:468–471

    Google Scholar 

  17. Couetdic Y, Michel-Briand Y, Barale T (1990) Anticorps anti-BCG (antigène 60) au cours d'infections non-mycobactériennes. Med Mal Infect 20:174–176

    Google Scholar 

  18. Daniel TM (1990) The rapid diagnosis of tuberculosis:A selective review. J Lab Clin Med 116:277–282

    Google Scholar 

  19. Daniel TM, Debanne SM (1987) The serodiagnostic of tuberculosis and other mycobacterial diseases by enzymelinked immunosorbent assay. Am Rev Respir Dis 135:1137–1151

    Google Scholar 

  20. Del Pezzo A, De Filippis E, Guletta E (1990) Serodiagnosis of mycobacterioses in HIV-1 positive patients. First Int Conf Pathog Mycobact Inf. Stockholm, Sweden, June 27–29

  21. Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose (1990) Mitteilung des Deutschen Zentralkomitees zur Bekämpfung der Tuberkulose. Pneumologie 44:760–761

    Google Scholar 

  22. Fabre I, L'Homme O, Bruneteau M, Michel G, Cocito C (1986) Chemical composition of antigen 60 from M. bovis BCG. Scand J Immunol 24:591–602

    Google Scholar 

  23. Fine PE, Rodrigues LC (1990) Mycobacterial diseases. Lancet. I:1016–1018

    Google Scholar 

  24. Gevaudan MJ, Bollet C, De Micco Ph (1991) Utilisation du test ELISA-Antigène 60 pour un serodiagnostic des infections à mycobactéries. Spectra Biologie (in press)

  25. Gevaudan MJ, Bollet C, Goldstein A, Mallet MN, De Micco Ph (1990) The enzyme-linked immunosorbent assay method for IgG antibody to antigen-60 in cerebro-spinal fluid of patients with tuberculous meningitis. First Intern Conf Pathog Mycobact Inf. Stockholm, Sweden, June 27–29

  26. Gomez-Mampaso E, Palenque E, Sanchez M, Rivera MJ, de la Torre F, Gonzalez A, Ladron G, Silvestre R, March MJ, Ortega A (1991) Deteccion de anticuerpos IgG frente al antigeno 60 para el diagnostico de la tuberculosis humana:Resultados de un estudio multicentrico. Rev Esp Microbiol Clin (in press)

  27. Grange JM, Kardjito T (1982) Serological tests for tuberculosis:Can the problem of low specificity be overcome? Indian J Chest Dis 24:108–117

    Google Scholar 

  28. Grange JM (1984) The humoral immune response in tuberculosis:its nature, biological role and diagnostic usefulness in Fow W, Grosset J, Styblo K (eds) Advances in tuberculosis research, vol 21. Karger, Basel:1–78

    Google Scholar 

  29. Grange JM, Gibson J, Nassau E, Kardjito T (1980) Enzyme-linked immunosorbent assay (ELISA):A study of antibodies toM. tuberculosis in the IgG, IgA and IgM classes in tuberculosis, sarcoidosis and Crohn's disease. Tubercle 61:145–152

    Google Scholar 

  30. Grange JM, Laszlo A (1990) Serodiagnostic tests for Tuberculosis-A Need for Assessment of their Operational Predictive Accuracy and Acceptability. Bull WHO 68:571–577

    Google Scholar 

  31. Grosset JH, Li BH (1989) Controlled clinical trial for evaluation of antimicrobial drug activity against M. leprae. Int J Leprosy 57:529–533

    Google Scholar 

  32. Guletta E, Del Passo M, Sanduzzi A, Bariffi F, Covelli I (1988) Serodiagnosis survey of tuberculosis by a new elisa method. Europ J Epidemiol 2:223–226

    Google Scholar 

  33. Hampson SJ, Thompson J, Moss MT, Portaels F, Green EP, Hermon-Taylor J, McFadden JJ (1989) DNA probes demonstrate a single highly conserved strain of Mycobacterium avium infecting AIDS patients. Lancet 335:65–68

    Google Scholar 

  34. Harboe M (1981) Antigens of PPD, Old Tuberculin and autoclaved mycobacterium bovis BCG studied by Immunoelectrophoresis. Am Rev Respir Dis 124:80–87

    Google Scholar 

  35. Hart PDA, Sutherland I, Thomas J (1967) The immunity conferred by effective BCG and vole bacillus vaccines, in relation to individual variations in induced tuberculin sensitivity and to technical variations in the vaccines. Tubercle 48:201–210

    Google Scholar 

  36. Huggett S, Friedrich O, Freitag V, Kaukel E (1990) Serologische A60-IgG und A60-IgM Bestimmung bei Tuberculose (Myko-Elisa). 26. Tagung der Gesellschaft für Lungen-und Atmungsforschung in Bochum, 6.–8. Dezember

  37. Jackowski M, Lenci G, Ebert W, Schulz V (1990) Die Diagnostik der Tuberculose mit dem A60 TB-Test. Pneumologie 44, Poster 243

  38. Juker MT, Falkinham JO (1990) Epidemiology of infection by non-tuberculous Mycobacteria. IX. Evidence for two DNA homology groups among small plasmids in M. avium, M. intracellulare and M. scrofulaceum. Am Rev Respir Dis 142:858–862

    Google Scholar 

  39. Lind A, Bentzon MW, Larsson LO (1988) Further results on sensitisin studies in Göteborg, Sweden. Ninth annual meeting Europ Society Mycob. 4th, 5th and 6th July. Poster 27

  40. Lopez-Hontangas JL, Pardo Serrano FJ, Garcia del Busto A, Cascales Ramos P, Fandos E, Galiano JU (1990) Serologia de la tuberculosis:deteccion de anticuerpos IgG e IgM. Determinacion del valor umbral de IgG. Rev Esp Microbiol Clin 5:618–620

    Google Scholar 

  41. McFadden JJ, Houdayer C (1988) No evidence for antibodies to mycobacterial A60 antigen in Crohn's Disease sera by enzyme-linked-immunosorbent assay. J Med Microbiol 25:295–298

    Google Scholar 

  42. Maes R (1989) Incidence of inapparent active mycobacterial infections in France detected by an IgG serological test based on antigen 60. Med Microbiol Immunol 178:315–321

    Google Scholar 

  43. Maes R (1991) Evaluation of the avidity of IgG antimycobacterial antibodies in tuberculous patients' serum by an A60 immunoassay. Eur J Epidemiol 7:188–190

    Google Scholar 

  44. Maes R, Homasson JP, Kubin M, Bayer M (1989) Development of an enzyme-immunoassay for the serodiagnostic of tuberculosis and mycobacteria. Med Microbiol Immunol 178:323–335

    Google Scholar 

  45. Manrique A, Gomez JL, Espinosa P, Jimenez MS (1989) Nivel de anticuerpos frente a antigeno 60 en dos grupos de poblacion sana. II Reunion nacional del grupo espanol de micobacteriologia. Barcelona 26–28 Mayo:P-DRO8

  46. Mattar S, Broquetas J, Sauleda J, Carceller A, Gea J, Aran X, Torres JM (1989) Deteccion de anticuerpos IgG con el metodo Elisa en pacientes tuberculosos utilisando el antigeno 60. Rev Esp Microbiol Clin 2:97–102

    Google Scholar 

  47. Mongur KA, Khalegue KA (1957) Preparation of a purified antigen from Kednowsky's bacillus for complement fixation test for Kala Azar. Trans Roy Soc Trop Med Hyg 51:527–532

    Google Scholar 

  48. Niessner B, Laumen R, Vilcovsky HG (1990) Korrelation des Spiegels des Anti-A60 Mykobakterium IgG mit Beginn und Behandlungsverlauf der Tuberkulose. 34. Kongress Deutscher Gesellschaft Pneumologie Tuberkulose, Bochum 19–22 September

  49. Peters M, Schurmann D, Mayer AC, Hetzer R, Pohle HD, Ruf B (1989) Immunosuppression and mycobacteria other than Mycobacterium tuberculosis:results from patients with and without HIV infections. Epidem Inf 103:293–300

    Google Scholar 

  50. Pfeuffer HP, Steinkirscher G, Schweisfurth H (1990a) Serologischer Tuberkulotest und Tuberkulin-Tine Test im Vergleich und in Kombination. Atemsweg-und Lungenkrankheiten 16:350–351

    Google Scholar 

  51. Pfeuffer HP, Steinkirscher G, Schweisfurth H (1990b) Serologische Tuberkulosediagnostik mit einem A60-Antikörper Testsystem. Pneumologie 44:Poster 243

  52. Raheman SF, Wagner S, Mauch H, Vasuderia ND, Ingole DL (1988) Evaluation of a dual antigen elisa test for the serodiagnosis of tuberculosis. Bull WHO 66:203–209

    Google Scholar 

  53. Roche PW, Britton WJ, Failbus SS, Williams D, Pradhan HM, Theuvenet WJ (1990a) Operational Value of Serological Measurements in Multibacillary Leprosy Patients:Clinical and Bacteriological Correlates of Antibody Responses. Int J Lepr 58:480–490

    Google Scholar 

  54. Roche PW, Britton WJ, Failbus SS, Ludwig H, Theuvenet WJ, Adiga RB (1990b) Heterogeneity of Serological Responses in Paucibacillary Leprosy — Differential Responses to Protein and Carbohydrate Antigens and Correlation with Clinical Parameters. Int J Lepr 58:319–327

    Google Scholar 

  55. Saad MHF, Medeiros MA, Gallo MEN, Gontijo PP, Fonseca LS (1990) IgM immunoglobulins reacting with the phenolic glycolipid antigen fromM. leprae in sera of leprosy patients and their contacts. Mem Inst Oswaldo Cruz, Rio de Janeiro 85:191–194

    Google Scholar 

  56. Sada E, Brennan PJ, Herrera T, Torres M (1990) Evaluation of Lipoarabinomannan for the serological Diagnosis of Tuberculosis. J Clin Microbiol 28:2587–2590

    Google Scholar 

  57. Schaberg T, Lode H (1990) Diagnostik der Tuberkulose. Dtsch med Wschr 115:1795–1798

    Google Scholar 

  58. Shinnick JM, Vodkin MH, Williams JL (1988) The Mycobacterium tuberculosis 65 kDa protein is a heat shock protein which corresponds to common antigens and to the E. coli EL protein. Inf Immun 56:446–451

    Google Scholar 

  59. Sindic CJM, Baelden MC, Bukasa KSS, Laterre C, Cocito C (1990) Intrathecal synthesis of anti-mycobacterial antibodies in patients with tuberculous meningitis:An immunoblotting study. J Neurol Neurosurg Psych 53:662–666

    Google Scholar 

  60. Snider DRJr (1989) Research towards global control and prevention of tuberculosis with emphasis on vaccine development. Rev Infect Dis 2:S336-S339

    Google Scholar 

  61. Thayer WRJr, Coutu JA, Chiodini RJ, Van Kruiningen HJ, Merkal RS (1984) Possible Role of Mycobacteria in Inflammatory Bowel Disease. Dig Dis Sci 29:1073–1079

    Google Scholar 

  62. Voigt T, Velcovsky HG, Sitte J, Laumen R (1990) A60-Antikörperspiegel bei Patienten mit Tuberkulosen und anderen pulmonaren Erkrankungen. 26. Tagung der Gesellschaft für Lungen-und Atmungsforschung in Bochum, 6.–8. Dezember

  63. Wirrmann C (1990) Public health application of a serological test for tuberculosis:Study of the incidence of inapparent infections among the employees of an alsatian supermarket. Eur J Epidemiol 6:304–308

    Google Scholar 

  64. Youmans GP (1979) Development of delayed (Tuberculin) hypersensitivity in tuberculosis. In:“tuberculosis” GP Youmans (ed) Saunders, Philadelphia, pp 209–224

    Google Scholar 

  65. Young RA, Bloom BR, Grosskinski CM, Ivanyi J, Thomas D, Davis RW (1985) Dissection of Mycobacterium tuberculosis antigens using recombinant DNA. Proc nat Acad Sci (Washington) 82:2583–2590

    Google Scholar 

  66. Zatla F, Petithory JC (1989) L'élisa avec l'antigène 60 dans le diagnostic de la tuberculose:réactions croisées dans la Leishmaniose viscérale. Technique et Biologie 5:220–225

    Google Scholar 

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  1. Anda Biologicals, Strasbourg, France

    R. Maes

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Maes, R. Clinical usefulness of serological measurements obtained by antigen 60 in mycobacterial infections: Development of a new concept. Klin Wochenschr 69, 696–709 (1991). https://doi.org/10.1007/BF01649439

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