Abstract
Two ELISA tests (IgG and IgM) for the serodiagnosis of tuberculosis, both based on antigen 60 (A60) ofM. bovis BCG, were applied to 1,644 controls and patients to analyse the immune response in different forms of this infectious disease. Out of 200 healthy individuals, 148 being tuberculin —positive BCG-vaccinated adults, only 10 contacts — nurses of the pneumology department and laboratory technicians of the mycobacterial laboratory — were found positive for anti-A60 IgG. One quarter of hospitalized patients affected by non-tuberculous pneumopathies (194 in total) were found weakly positive for anti-A60 IgG. We suppose that these positive cases have suffered from inapperant infections and are in a “persistent state”. Out of 344 cases of primary pulmonary tuberculosis, 88% were positive for anti-A60 IgG and 75% for the corresponding IgM. Among 97 cases of primary extra-pulmonary tuberculosis, 94% were found IgG positive and 33% IgM positive. The difference between active and inactive post-primary (chronic) tuberculosis was striking: about 100% of both pulmonary and extra-pulmonary cases (367 altogether) had high titers of anti-A60 IgG but IgM positivity was observed in only 15% of the cases, whereas in inactive and quiescent non-cavitary tuberculosis (442 cases), 57% of the patients were weakly positive for anti-A60 IgG and none were positive for IgM. Kinetics of synthesis of anti-A60 IgG and IgM were analysed in primary and post-primary (chronic) active tuberculosis. The IgM tracing immune response to A60 was shorter and lower during primary tuberculosis as compared to post-primary tuberculosis. Our findings point to the high prognostic value of the A60- ELISA test for tuberculosis. Anti-A60 IgM mark initial stages of the disease or reactivation processes whereas anti-A60 IgG last longer than IgM and provide an evaluation of the intensity of the infectious process. Repeated serological tests allow monitoring of the course of the infection and the efficacy of therapy. The test is negative in healthy BCG-vaccinated persons (tuberculin-positive) and healed tuberculous infection cases. The combined use of both IgG and IgM tests helps in the correct diagnosis of “false positive” cases.
Similar content being viewed by others
References
Baelden M. C.,Yanderelst B.,Dieng M.,Prignot J. andCocito C. (1990): Serological analysis of human tuberculosis by an ELISA immunoassay with mycobacterial antigen-60 - Scand. J. Inf. Dis.22: 63–73.
Benjamin R. G. andDaniel T.M. (1982): Serodiagnosis of tuberculosis using the ELISA of antibody toMycobacterium tuberculosis antigen 5 - Am. Rev. Respir. Dis.126: 1013–1016.
Casal M. andLinares M.J., (1988): Diagnostico serologico de la tuberculosis - Rev. Esp. Microbiol. Clin.3: 491–492.
Charpin D.,Herbault M.,Gevaudan M.J.,Saadjian M.,De Micco Ph,Arnaud A.,Vervloet D. andCharpin J. (1990): Value of ELISA using A60 antigen in the diagnosis of active pulmonary tuberculosis - Am. Rev. Respir. Dis.142: 380–384.
Chatterjee B.R. (1990): Controlled clinical trials: comments on the contribution of Pr. Grosset - Int. J. Leprosy58: 376–378.
Closs O.,Harboe M.,Axelsen N.H.,Bunch K. andMagnusson M. (1980): The antigens ofMycobacterium bovis strain BCG, studied by crossed Immunoelectrophoresis: a Reference System -Scand. J. Immunol.12: 249–263.
Cocito C.,Baelden M.C. andBenoit C.H. (1987): Immunological properties of Antigen 60 of BCG -Scand. J. Immunol.25: 579–585.
Cocito C. andYanlinden F. (1986): Preparation and properties of antigen 60 fromMycobacterium bovis -Clin. Exp. Immunol.66: 262–268.
Daniel T.M. (1990): The rapid diagnosis of tuberculosis: A selective review - J. Lab. Clin. Med.116: 277–282.
Daniel T.M. andDebanne S.M. (1987): The serodiagnosis of tuberculosis and other mycobacterial diseases by ELISA - Am. Rev. Respir. Dis.135: 1137–1151.
Daniel T.M.,Debanne S.M. andVanderkuyp F. (1985): ELISA usingM. tuberculosis antigen 5 for the serodiagnosis of tuberculosis - Chest.88: 388–392.
Fabre L,L 'Homme O.,Bruneteau M.,Michel G. andCocito C. (1986): Chemical composition of antigen 60 fromM. bovis BCG - Scand. J. Immunol.24: 591–602.
Ferreira P.,Soares R. andArala-Chaves M. (1991): Susceptibility to infection withM. avium is paradoxically correlated with increased synthesis of specific anti-bacterial antibodies - Intern. Immunol.3: 445–452.
Fine P.E. andRodrigues L.C. (1990): Mycobacterial diseases - Lancet April28: 1016–1018.
Grange J.M. (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- BaselI: pp78.
Grange J.M.,Gibson J.,Nassau E. andKardjito T. (1990): Enzyme-linked immunosorbent assay (ELISA): A study of antibodies toM. tuberculosis in the IgG, IgA and IgM classes in tuberculosis, sarcoidosis and Crohn' disease - Tubercle61: 145–152.
Grosset J.H. andLi B.H. (1989): Controlled clinical trial for evaluation of antimicrobial drug activity againstM. leprae - Int. J. Leprosy57: 529–533.
Guletta E.,Del Passo M.,Sanduzzi A.,Bariffi F. andCovelli I. (1988): Serodiagnosis survey of tuberculosis by a new ELISA method - Eur. J. Epidemiol.2: 223–226.
Harboe M. (1981): Antigens of PPD, Old Tuberculin and autoclavedMycobacterium bovis BCG studied by Immunoelectrophoresis - Am. Rev. Respir. Dis. 124: 80–87.
Harboe M.,Closs O.,Bjorvatn B. andBjune G. (1977): Antibodies against BCG antigen 60 in mycobacterial infection - Brit. Med. J.2: 430–433.
Harboe M.,Wiker H.,Duncan R.,Garcia M.,Dukes T. et al. (1990): Protein G based enzyme-linked immunosorbent assay for anti MPB 70 antibodies in bovine tuberculosis - J. Clin. Microbiol.28: 913–921.
Krambovitis E. (1986): Detection of antibodies toM. tuberculosis plasma membrane antigen by ELISA - J. Med. Microbiol.21: 257–264.
Krambovitis E. (1987): Serodiagnosis of tuberculosis in perspective — Serodiagn. Immunoth.1: 7–19.
Maes R.,Homasson J.P.,Kubin M. andBayer M. (1989): Development of an enzyme-immunoassay for the serodiagnosis of tuberculosis and mycobacteria -Med. Microbiol. Immunol.178: 323–335.
Maes R. (1989): Incidence of inapparent active mycobacterial infections in France detected by an IgG serological test based on antigen 60 - Microbiol. Immunol.178: 315–321.
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.
Maes R. (1991): Clinical Usefulness of Serological Measurements Obtained by Antigen 60 in Mycobacterial Infections: Development of a New Concept - Klin. W ochenschr.69: 696–709.
Mandler F.,Calzavara M.P.,Cirianni F.,DeFinis M.,Mantellini P. V.,Passerini-Tosi C.,Peona V.,Rossetti R. andScarpazza G. (1991): Sierodiagnosi della tubercolosi: rilievo delle IgG con il test ELISA antigene 60. Indicazioni diagnostiche - Medicina Toracica13: 67–72.
Mattar S.,Broquetas J.,Sauleda J.,Carceller A.,Gea J.,Aran X. andTorres J.M. (1989): Deteccion de anticuerpos IgG con el methoo ELISA en pacientes tuberculosos utilisando el antigeno 60 - Rev. Esp. Microbiol. Clin.2: 97–102.
Raheman S.F.,Wagner S.,Mauch H.,Vasderia N.D., andIngole D.L. (1988): Evaluation of a dual antigen ELISA test for the serodiagnosis of tuberculosis -Bull. WHO66: 203–209.
Reggiardo Z.,Vasquez E. andSchnaper L. (1980): ELISA test for antibodies against mycobacterial glycolipids - J. Immunol. Methods.34: 55–60.
Roche P. W.,Britton W.J.,Failbus S.S.,Williams D.,Pradhan H.M. andTheuvenet W.J. (1990): Operational Value of Serological Measurements in Leprosy Patients: Clinical and Bacteriological Correlates of Antibody Responses - Int. J. Leprosy58: 480–490.
Shinnick J.M.,Vodkin M.H. andWilliams J.L. (1988): TheMycobacterium tuberculosis 65 kDa protein is a heat shock protein which corresponds to common antigens and to theE. coli EL protein - Inf. Immun.56: 446–451.
Sindic C.J.M.,Bealden M.C.,Bukasa K.S.S.,Laterre C.,Cocito C. (1990): Intrathecal synthesis of antimycobacterial antibodies in patients with tuberculous meningitis: An immunoblotting study -J. Neurol. Neurosurg. Psych.53: 662–666.
Stanford J.L. (1991): Improving on BCG - A.P.M.I.S.99: 103–113.
Thole J.E.R.,Dauwerse H.G.,Das P.K.,Groothuis D.G.,Schouls L.M. andVanEmbden J.D.A. (1985): Cloning ofMycobacterium bovis BCG DNA and expression of antigen inEscherichia coli - Inf. Immun.50: 800–806.
Toman K. (1981): Sensitivity, specificity and predictive value of diagnostic tests - Bull. Int. Union Tuberc.56: 18–28.
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.
Zatla F. andPetithory J.C. (1989): L'élisa avec l'antigène 60 dans le diagnostic de la tuberculose: réactions croisées dans la Leishmaniose viscérale -Technique et Biologie5: 220–225.
Zeiss C.R.,Kalish S.B. andErlich K.S. (1984): IgG antibody to purified protein derivative by ELISA in the diagnostic of pulmonary tuberculosis - Am. Rev. Respir. Dis.130: 845–848.
Author information
Authors and Affiliations
Additional information
Corresponding author.
Rights and permissions
About this article
Cite this article
Gevaudan, M.J., Bollet, C., Charpin, D. et al. Serological response of tuberculosis patients to antigen 60 OF BCG. Eur J Epidemiol 8, 666–676 (1992). https://doi.org/10.1007/BF00145382
Issue Date:
DOI: https://doi.org/10.1007/BF00145382