Serodiagnosis of tuberculosis by enzyme immunoassay using A60 antigen
2001; Elsevier BV; Volume: 7; Issue: 7 Linguagem: Inglês
10.1046/j.1198-743x.2001.00263.x
ISSN1469-0691
AutoresAyşe Yüce, M. Yućesoy, Şermin Genç, Murat Sayan, Eyüp Sabri Uçan,
Tópico(s)Bacteriophages and microbial interactions
ResumoTuberculosis continues to be a worldwide public-health problem, with an estimated 90 million new cases and 30 million deaths during the last decade of the 20th century [1Pilheu JA Tuberculosis 2000: problems and solutions.Int J Tuberc Lung Dis. 1998; 2: 696-703PubMed Google Scholar]. It has been an ever-present health threat in developing countries. At the same time, it has been increasing in Europe and the USA following the emergence of AIDS in the world [2Festenstein F Grange JM Tuberculosis and the acquired immune deficiency syndrome.J Appl Bacteriol. 1991; 71: 19-30Crossref PubMed Google Scholar]. The prevalence of tuberculosis in Turkey is 0.35%, and 30 000–40000 new cases are being reported every year [3Erbaðcý A Dündar V Çetinkaya F Kazgöl N Erem AR Tüberkülozun serolojik tanýsýnda antijen A60′a karþý antikorlarýn taný deðeri ve çalýþmaya alýnan popülasyonun önemi.Klimik Dergisi. 1992; 5: 56-59Google Scholar]. An estimated 2 billion people are currently infected with Mycobacterium tuberculosis and Mycobacterium intracellulare complex throughout the world [4Shinnick TM King CH Quinn FD Molecular biology, virulence and pathogenicity of mycobacteria.Am J Med Sci. 1995; 309: 92-98Abstract Full Text PDF PubMed Scopus (47) Google Scholar]. The rates of morbidity and mortality are also rising as a result of multidrug-resistant strains [5Koneman EW Allen SD Janda WM Schreckenberger PC Winn WC Color Atlas and Textbook of Diagnostic Microbiology. Mycobacteria. 5th edn. Lippincott‐Raven, Philadelphia1997: 893-952Google Scholar]. The diagnosis of mycobacterial diseases depends upon identifying the infecting organism in the secretion or tissues. However, there are several limitations of this method. One is that Mycobacterium tuberculosis is usually present in undetectable numbers (for smear 5 × 103 to 5 × 104 bacilli/mL, and for culture 10–100 bacilli/mL), so that it is recognized for the most part in advanced cases [6Daniel TM Debanne SM The serodiagnosis of tuberculosis and other mycobacterial diseases by enzyme‐linked immunosorbent assay.Am Rev Respir Dis. 1987; 135: 1137-1151PubMed Google Scholar]. Second, most mycobacteria are slow-growing organisms and require long periods of time to culture, even if the most advanced techniques are used [6Daniel TM Debanne SM The serodiagnosis of tuberculosis and other mycobacterial diseases by enzyme‐linked immunosorbent assay.Am Rev Respir Dis. 1987; 135: 1137-1151PubMed Google Scholar, 7Kalish LR Radin RC Phair JP Levitz D Zriss R Metzger E Use of an enzyme‐linked immunosorbent assay technique in the differential diagnosis of active pulmonary tuberculosis in humans.J Infect Dis. 1983; 147: 523-530Crossref PubMed Scopus (48) Google Scholar]. Third, negative smears are usually obtained until cavities form [8Charpin D Herbault H Gevaudan MJ et al.Value of ELISA using A60 antigen in the diagnosis of active pulmonary tuberculosis.Am Rev Respir Dis. 1990; 142: 380-384Crossref PubMed Scopus (62) Google Scholar]. Thus, a fast, easy and reliable method was needed for the diagnosis of tuberculosis. Among several serologic techniques, it has been concluded that enzyme immunoassay (EIA) is a sensitive, reliable, simple and rapid method [6Daniel TM Debanne SM The serodiagnosis of tuberculosis and other mycobacterial diseases by enzyme‐linked immunosorbent assay.Am Rev Respir Dis. 1987; 135: 1137-1151PubMed Google Scholar]. Several purified antigens, such as 38-kDa protein, 85A antigen, lipoarabinomannan, plasma membrane antigen, antigen 5 and antigen 60 (A60), have been used for the serodiagnosis of tuberculosis [8Charpin D Herbault H Gevaudan MJ et al.Value of ELISA using A60 antigen in the diagnosis of active pulmonary tuberculosis.Am Rev Respir Dis. 1990; 142: 380-384Crossref PubMed Scopus (62) Google Scholar, 9Julian E Matas L Ausina V Luquin M Detection of lipoarabinomannan antibodies in patients with newly acquired tuberculosis and patients with relapse tuberculosis.J Clin Microbiol. 1997; 35: 2663-2664PubMed Google Scholar, 10Wilkinson RJ Haslov K Rappuoli R et al.Evaluation of the recombinant 38‐kilodalton antigen of Mycobacterium tuberculosis as a potential immunodiagnostic reagent.J Clin Microbiol. 1997; 35: 553-557PubMed Google Scholar, 11Daniel TM Debanne SM Van Der Kuyp F Enzyme‐linked immunosorbent assay using Mycobacterium tuberculosis antigen 5 and PPD for the serodiagnosis of tuberculosis.Chest. 1985; 88: 388-392Crossref PubMed Scopus (34) Google Scholar, 12Simonney N Molina JM Molimard M Oksenhendler E Lagrange H Comparison of A60 and three glycolipid antigens in an ELISA test for tuberculosis.Clin Microbiol Infect. 1996; 2: 214-222PubMed Scopus (21) Google Scholar]. This study was undertaken to evaluate the usefulness of the EIA method using A60 antigen for the diagnosis of different forms of tuberculosis in Turkish patients. Serum samples were collected from four groups of patients and the control group. Sera from active tuberculosis patients were collected before chemotherapy, and kept at −70 °C until the EIA procedure. Group 1 consisted of 112 patients (74 male, 38 female) with a mean age of 36.32 ± 12.25 years, who were diagnosed as having active lung tuberculosis by positive smear and/or culture and clinical and radiologic findings. They were all anti-HIV negative. Group 2 consisted of 40 patients (29 male, 11 female) with a mean age of 59.47 ± 13.36 years, with the diagnosis of inactive lung tuberculosis by radiologic findings and patient history. Three of the patients had a history of tuberculosis during the previous 2 years, and 26 of them had a history of tuberculosis before that period. Eleven of 40 patients had no tuberculosis history but had findings related to a previous infection in their chest X-rays. None of their sputum smears and cultures were positive. Group 3 consisted of 21 patients (9 male, 12 female) with a mean age of 36.0 ± 14.37 years, diagnosed as having miliary tuberculosis by radiologic findings and positive cultures of various specimens (four sputum, one bronchoalveolar lavage, two transbronchial, one larynx, one liver, three lymph node biopsies). All cases had scattered miliary densities on their chest X-rays. Two patients also had cavities in their radiographs. They were all anti-HIV negative. Group 4 consisted of 41 patients (17 female, 24 male) with a mean age of 34.18 ± 12.45 years, with various lung diseases other than tuberculosis. Among these patients, 21 had lung tumors, while seven, four and four of them had bronchiectasis, chronic obstructive pulmonary disease/chronic bronchitis and pneumonia, respectively. The diagnoses of the rest of the cases were: bronchial asthma (one), sarcoidosis (one), idiopathic hemoptysis (one), lung fibrosis (one) and asbestosis (one). Group 5 consisted of 38 heathy individuals (19 male, 19 female) with a mean age of 36.86 ± 14.43 years. The serum samples were kept at −70 °C until tested. Sera of all the patients and healthy individuals were searched for IgG and IgM antibodies against A60 by micro EIA (Eurospital spa, Trieste, Italy). IgA antibodies were only investigated in the sera of 135 patients and in all healthy individuals with the same method, according to the manufacturer's instructions. Calibrators were used in the IgG and IgA tests, so that the results were quantitated. For the IgM test, the results were given as –, ±, +. The cut-off points of EIA for each antibody were calculated from the results obtained with sera from the healthy group using the following formula: the mean value obtained from the healthy control group ± 2 standard deviation. The sensitivity, specificity and predictive values were estimated with the Epi Info Version 6 Program [13Dean AG Dean JA Coulombier D et al.Epi Info, Version 6: a word processing, database, and statistics program for epidemiology on microcomputers. Centers for Disease Control and Prevention, Atlanta, Georgia1994Google Scholar]. Statistical significance was determined by the chi-squared test and chi-squared test with Fisher's correction with the SPSS Program 6.0 [14SSPS, Inc SSPS for windows release 6.0. SPSS Inc., Chicago Ill1993Google Scholar]. The cut-off value for IgG EIA was calculated as 2 EU (EIA units). The numbers of positive cases for IgG in all groups are shown in Table 1. A comparison of the groups, according to the positivity rates of IgG, revealed a statistical difference (χ2 = 42.50, P = 0.0000). Patients with active tuberculosis showed a significantly higher positivity rate of IgG than healthy individuals and the patients with lung diseases other than tuberculosis (χ2 = 18.55, P = 0.00002, and χ2 = 27.31, P = 0.00000, respectively). At the same time, statistically important differences were observed between the active and inactive tuberculosis groups (χ = 9.68, P = 0.00186). The sensitivity, specificity and positive predictive and negative predictive values for IgG are shown in Table 2.Table 1The positivity rates for IgG, IgM and IgA for the groupsGroup numbernIgG positive (%)IgM positive (%)nIgA positive (%)111260 (53.6)49 (43.8)6450 (78.1)24010 (25.0)3 (7.5)4015 (37.5)32110 (47.6)1 (4.7)1914 (73.7)4416 (14.6)4 (9.8)123 (25.0)5382 (5.3)1 (2.6)383 (7.9) Open table in a new tab Table 2Sensitivity, specificity, positive predictive values and negative predictive values according to the groups considered for IgG, IgM and IgA EIAGroupsSensitivity (%)Specificity (%)Positive predictive value (%)Negative predictive value (%)(CI)(CI)(CI)(CI)IgGIgMIgAIgGIgMIgAIgGIgMIgAIgGIgMIgA1 and 553.643.878.194.797.492.196.898.094.340.937.071.4(43.9, 63.0)(34.5, 53.4)(65.7, 87.1)(80.9, 99.1)(84.6, 99.9)(77.5, 97.9)(87.8, 99.4)(88.0, 99.9)(83.4, 98.5)(30.7, 51.9)(27.7, 47.3)(56.5, 83.0)1 and 453.643.878.185.490.275.090.992.594.340.237.039.1(43.9, 63.0)(34.5, 53.4)(65.7, 87.1)(70.1, 93.9)(75.9, 96.8)(42.8, 93.3)(80.6, 96.3)(80.9, 97.6)(83.4, 98.5)(30.0, 51.3)(27.7, 47.3)(20.5, 61.2)1 + 3 and 552.637.677.194.797.492.197.298.095.536.430.864.8(43.8, 61.3)(29.5, 46.4)(66.3, 85.3)(80.9, 99.1)(84.6, 99.9)(77.5, 97.9)(89.4, 99.5)(88.0, 99.9)(86.6, 98.8)(27.1, 46.7)(22.9, 40.0)(50.6, 77.0)1 + 3 and 452.637.677.185.490.275.092.192.695.535.730.832.1(43.8, 61.3)(29.5, 46.4)(66.3, 85.3)(70.1, 93.9)(75.9, 96.8)(42.8, 93.3)(83.0, 96.7)(81.3, 97.6)(86.6, 98.8)(26.5, 46.1)(22.9, 40.0)(16.6, 52.4)1 + 3 and 252.637.677.175.092.562.587.594.381.032.330.856.8(43.8, 61.3)(29.5, 46.4)(66.3, 85.3)(58.5, 86.8)(78.5, 98.0)(45.8, 76.8)(77.8, 93.5)(83.4, 98.5)(70.3, 88.6)(23.1, 42.9)(22.9, 40.0)(41.1, 71.3)CI, confidence interval. Open table in a new tab CI, confidence interval. The number of cases positive for anti-A60 IgM in each group are shown in Table 1. A statistical difference was observed when the positivity rates of all the groups and groups 1 and 4 and 5 were compared (χ2 = 49.54, P = 0.0000, χ2 = 15.32, P = 0.00009, and χ2 = 21.59, P = 0.00000, respectively). The number of positive cases in the active tuberculosis group was significantly higher than the number of positive cases in the inactive tuberculosis group (χ2 =17.21, P = 0.00003). The sensitivity, specificity and positive predictive and negative predictive values for IgG are shown in Table 2. A60 IgA was detected in 50 of 64 cases of active and 14 of nine cases of miliary tuberculosis (Table 1). A statistical difference was detected between the positivity rates of all groups (χ2 = 56.93, P = 0.0000). There was also a statistically significant difference between groups 1 and 4 and 1 and 5 (χ2 = 35.21, P = 0.00067; χ2 = 47.11, P = 0.00000). The positivity rates of groups 1 and 2 were also compared for IgA, and a statistically important difference was observed (χ2 = 17.33, P = 0.00003). The sensitivity, specificity and positive predictive and negative predictive values for IgG are shown in Table 2. There was no statistical difference between the antibody responses of the smear-negative and smear-positive cases of groups 1 and 3 (P>0.05). There was also no statistically important difference between the culture-negative and culture-positive cases of group 3 (P>0.05). The development of mycobacterium infections entails a strong interaction of components of mycobacteria and the immune system of the host [15Chaparas SD The immunology of mycobacterial infections.CRC Crit Rev Microbiol. 1982; 9: 139-197Crossref Scopus (20) Google Scholar]. These mycobacterial components and the antibodies against them are valuable for the diagnostic assays of tuberculosis. One of the best known antigens is A60, which is the major heat-stable component of tuberculin and protein purified derivative (PPD). The sensitivity and specificity for IgG against A60 in pulmonary tuberculosis cases were found to be 36–91% and 68–98%, respectively [16Zou YL Zhang JD Chen MH Shi GQ Prignot J Cocito C Serological analysis of pulmonary and extrapulmonary tuberculosis with enzyme‐linked immunosorbent assays for anti‐A60 immunoglobulins.Clin Infect Dis. 1994; 19: 1084-1091Crossref PubMed Scopus (28) Google Scholar, 17Alifano M De Pascalis R Sofia M Faraone S Del Pezzo M Covelli I Detection of IgG and IgA against the mycobacterial antigen A60 with extrapulmonary tuberculosis.Thorax. 1998; 53: 377-380Crossref PubMed Scopus (22) Google Scholar, 18Caminero JA Rodriguez de Castro F Carillo T Lafargo B Diaz F Cabrera P Value of ELISA using A60 antigen in the serodiagnosis of tuberculosis.Respiration. 1994; 61: 283-286Crossref PubMed Scopus (10) Google Scholar, 19Turneer M Nerom EV Serological comparison of purified antigens 60 and 85A (P32) of Mycobacterium bovis BCG, and purified protein derivative in active pulmonary tuberculosis.Eur J Epidemiol. 1993; 9: 541-546Crossref PubMed Scopus (4) Google Scholar, 20Qadri SMH Smith KK Nonspecificity of the Anda A60‐tb ELISA test for serodiagnosis of mycobacterial disease.Can J Microbiol. 1992; 38: 804-806Crossref PubMed Scopus (11) Google Scholar, 21Gupta S Kumari S Banwalikar JN Gupta SK Diagnostic utility of the estimation of mycobacterial antigen A60 specific immunoglobulins IgM, IgA and IgG in the sera of cases of adult human tuberculosis.Tubercle Lung Dis. 1995; 76: 418-424Abstract Full Text PDF PubMed Scopus (49) Google Scholar, 22Baelden M Vanderelst B Dieng M Priignot J Cocito C Serological analysis of human tuberculosis by an ELISA with mycobacterial antigen 60.Scand J Infect Dis. 1990; 22: 63-73Crossref PubMed Scopus (39) Google Scholar, 23Maes R Clinical usefulness of serological measurements obtained by antigen 60 in mycobacterial infections: development of a new concept.Klin Wochenschr. 1991; 69: 696-709Crossref PubMed Scopus (22) Google Scholar, 24Li LF Lin MC Chen NH Hsieh MJ Lee CH Tsao TC Serodiagnosis of tuberculosis by enzyme‐linked immunosorbent assay for anti‐A60 and anti‐A38.Chang Keng I Hsueh Tsa Chih. 1998; 21: 258-264PubMed Google Scholar]. In this study, we found the sensitivity and specificity values for IgG A60 to be 53.6% and 94.7%, considering the active tuberculosis group and healthy individuals. These findings are in agreement with other results. Although the sensitivity rate is not as high as desired for a perfect diagnostic test, specificity values are very high. We found that 53.6% of active and 25.0% of inactive tuberculosis cases had IgG A60. These results are similar to or lower than those of other authors, who found the rate of positivity to be between 36% and 85% [16Zou YL Zhang JD Chen MH Shi GQ Prignot J Cocito C Serological analysis of pulmonary and extrapulmonary tuberculosis with enzyme‐linked immunosorbent assays for anti‐A60 immunoglobulins.Clin Infect Dis. 1994; 19: 1084-1091Crossref PubMed Scopus (28) Google Scholar, 22Baelden M Vanderelst B Dieng M Priignot J Cocito C Serological analysis of human tuberculosis by an ELISA with mycobacterial antigen 60.Scand J Infect Dis. 1990; 22: 63-73Crossref PubMed Scopus (39) Google Scholar, 25Landron de Guevara MC Gonzalez A Ortega A Saz JV Serological diagnosis of pulmonary tuberculosis using ELISA and the A60 antigen.Enferm Infect Microbiol Clin. 1992; 10: 17-19PubMed Google Scholar]. This may be because of the population chosen or the criteria that these authors used for diagnosis. According to our results, the IgG positivity rate was significantly higher than in healthy individuals and in patients with lung diseases other than tuberculosis. Our findings are consistent with the results of Alifano et al [17Alifano M De Pascalis R Sofia M Faraone S Del Pezzo M Covelli I Detection of IgG and IgA against the mycobacterial antigen A60 with extrapulmonary tuberculosis.Thorax. 1998; 53: 377-380Crossref PubMed Scopus (22) Google Scholar] and Turneer and Nerom [19Turneer M Nerom EV Serological comparison of purified antigens 60 and 85A (P32) of Mycobacterium bovis BCG, and purified protein derivative in active pulmonary tuberculosis.Eur J Epidemiol. 1993; 9: 541-546Crossref PubMed Scopus (4) Google Scholar]. In the present study, the sensitivity of A60 IgM antibody was found to be 43.8%. The sensitivity value for this antibody was previously reported to be between 24% and 80% [12Simonney N Molina JM Molimard M Oksenhendler E Lagrange H Comparison of A60 and three glycolipid antigens in an ELISA test for tuberculosis.Clin Microbiol Infect. 1996; 2: 214-222PubMed Scopus (21) Google Scholar, 16Zou YL Zhang JD Chen MH Shi GQ Prignot J Cocito C Serological analysis of pulmonary and extrapulmonary tuberculosis with enzyme‐linked immunosorbent assays for anti‐A60 immunoglobulins.Clin Infect Dis. 1994; 19: 1084-1091Crossref PubMed Scopus (28) Google Scholar, 21Gupta S Kumari S Banwalikar JN Gupta SK Diagnostic utility of the estimation of mycobacterial antigen A60 specific immunoglobulins IgM, IgA and IgG in the sera of cases of adult human tuberculosis.Tubercle Lung Dis. 1995; 76: 418-424Abstract Full Text PDF PubMed Scopus (49) Google Scholar, 23Maes R Clinical usefulness of serological measurements obtained by antigen 60 in mycobacterial infections: development of a new concept.Klin Wochenschr. 1991; 69: 696-709Crossref PubMed Scopus (22) Google Scholar, 24Li LF Lin MC Chen NH Hsieh MJ Lee CH Tsao TC Serodiagnosis of tuberculosis by enzyme‐linked immunosorbent assay for anti‐A60 and anti‐A38.Chang Keng I Hsueh Tsa Chih. 1998; 21: 258-264PubMed Google Scholar]. This wide range may be explained by the time of diagnosis, because IgM can be detected at the early stages of tuberculosis and after a short period of time it decreases, while IgG antibodies increase [23Maes R Clinical usefulness of serological measurements obtained by antigen 60 in mycobacterial infections: development of a new concept.Klin Wochenschr. 1991; 69: 696-709Crossref PubMed Scopus (22) Google Scholar]. In our study, the specificity of IgM was found to be 97.4%, which is a higher value than the sensitivity. A60 IgM EIA with high specificity could be used as a reliable test in the diagnosis of pulmonary tuberculosis when the result is positive. We found the positivity rates of IgA antibody to be 78.1%, 73.7% and 37.5% for the active, miliary and inactive tuberculosis cases, respectively. These values are in agreement with the results of Gupta et al [21Gupta S Kumari S Banwalikar JN Gupta SK Diagnostic utility of the estimation of mycobacterial antigen A60 specific immunoglobulins IgM, IgA and IgG in the sera of cases of adult human tuberculosis.Tubercle Lung Dis. 1995; 76: 418-424Abstract Full Text PDF PubMed Scopus (49) Google Scholar]. Our sensitivity and specificity values according to the IgA test are 78.1% and 92.1%. To our knowledge, this is the first study to consider IgA serologic testing against A60 in various cases of tuberculosis in a Turkish population. Our results indicate that A60 IgA antibody seems to be a useful diagnostic test for active tuberculosis cases. The positivity rates of IgG, IgM and IgA for the miliary tuberculosis group were 47.6%, 4.7% and 73.7%, respectively. Very few data are currently available concerning the usefulness of IgA A60 antibody testing in miliary tuberculosis cases. Zou et al [16Zou YL Zhang JD Chen MH Shi GQ Prignot J Cocito C Serological analysis of pulmonary and extrapulmonary tuberculosis with enzyme‐linked immunosorbent assays for anti‐A60 immunoglobulins.Clin Infect Dis. 1994; 19: 1084-1091Crossref PubMed Scopus (28) Google Scholar] and Gupta et al [21Gupta S Kumari S Banwalikar JN Gupta SK Diagnostic utility of the estimation of mycobacterial antigen A60 specific immunoglobulins IgM, IgA and IgG in the sera of cases of adult human tuberculosis.Tubercle Lung Dis. 1995; 76: 418-424Abstract Full Text PDF PubMed Scopus (49) Google Scholar] searched for these antibodies in miliary tuberculosis cases and reported the sensitivities of IgG as 76% and 91.6%, those of IgM as 50% and 45%, and those of IgA as 88.4% and 54%. The specificity values were found to be over 90% for all antibodies. It can be concluded that IgG and IgA A60 antibodies should be considered for miliary tuberculosis cases which are difficult to diagnose and usually require invasive procedures. The positivity rates of the antibodies can be considered to be relatively low when compared to the culture and smear positivity rates in group 1 (100% and 91%, respectively). However, the detection of antibody response can be important, especially in smear-negative cases, since antibody response is not statistically different between smear-negative and smear-positive cases. At the same time, the disadvantages of the classical techniques mentioned above should be considered. In our study, we found the rates of IgG, IgM and IgA A60 positivity to be 5.3%, 2.6% and 7.9% for the healthy individuals, and 14.6%, 9.8% and 25.0% for the patients with various lung diseases, respectively. The diagnosis of the patients who gave false-positive results were pneumonia and lung carcinoma in the group of non-tuberculous lung diseases. The rates of IgG A60 for these groups were found to be 0.38–23.8% and 6–55%, respectively, in previous studies [16Zou YL Zhang JD Chen MH Shi GQ Prignot J Cocito C Serological analysis of pulmonary and extrapulmonary tuberculosis with enzyme‐linked immunosorbent assays for anti‐A60 immunoglobulins.Clin Infect Dis. 1994; 19: 1084-1091Crossref PubMed Scopus (28) Google Scholar, 17Alifano M De Pascalis R Sofia M Faraone S Del Pezzo M Covelli I Detection of IgG and IgA against the mycobacterial antigen A60 with extrapulmonary tuberculosis.Thorax. 1998; 53: 377-380Crossref PubMed Scopus (22) Google Scholar, 20Qadri SMH Smith KK Nonspecificity of the Anda A60‐tb ELISA test for serodiagnosis of mycobacterial disease.Can J Microbiol. 1992; 38: 804-806Crossref PubMed Scopus (11) Google Scholar, 22Baelden M Vanderelst B Dieng M Priignot J Cocito C Serological analysis of human tuberculosis by an ELISA with mycobacterial antigen 60.Scand J Infect Dis. 1990; 22: 63-73Crossref PubMed Scopus (39) Google Scholar, 23Maes R Clinical usefulness of serological measurements obtained by antigen 60 in mycobacterial infections: development of a new concept.Klin Wochenschr. 1991; 69: 696-709Crossref PubMed Scopus (22) Google Scholar]. Zou et al [16Zou YL Zhang JD Chen MH Shi GQ Prignot J Cocito C Serological analysis of pulmonary and extrapulmonary tuberculosis with enzyme‐linked immunosorbent assays for anti‐A60 immunoglobulins.Clin Infect Dis. 1994; 19: 1084-1091Crossref PubMed Scopus (28) Google Scholar] reported two false-positive results for IgM and IgA antibodies; however, they mentioned one false-positive case in the group of healthy individuals. They also pointed out three instances of false positivity among 205 patients with lung diseases other than tuberculosis. Alifano et al [17Alifano M De Pascalis R Sofia M Faraone S Del Pezzo M Covelli I Detection of IgG and IgA against the mycobacterial antigen A60 with extrapulmonary tuberculosis.Thorax. 1998; 53: 377-380Crossref PubMed Scopus (22) Google Scholar] found similar false-positive results. These results may be due either to subclinical infection with environmental non-tuberculous mycobacteria that also express A60, or to the presence in the host of commensal nonpathogenic mycobacteria [26Cocito C Properties of the mycobacterial antigen complex A60 and its applications to the diagnosis and prognosis of tuberculosis.Chest. 1991; 100: 1687-1693Crossref PubMed Scopus (65) Google Scholar, 27Alifano M Sofia M Mormile M et al.IgA immune response against the mycobacterial antigen A60 in patients with active pulmonary tuberculosis.Respiration. 1996; 63: 292-297Crossref PubMed Scopus (27) Google Scholar]. The dysregulation of the humoral immune response might be another cause of non-tuberculous disease [26Cocito C Properties of the mycobacterial antigen complex A60 and its applications to the diagnosis and prognosis of tuberculosis.Chest. 1991; 100: 1687-1693Crossref PubMed Scopus (65) Google Scholar]. Dhand et al [28Dhand R Ganguly NK Vaishnavi C Gilhotra R Malýk SK False‐positive reactions with enzyme‐linked immunosorbent assay of Mycobacterium tuberculosis antigens in pleural fluid.J Med Microbiol. 1988; 26: 241-243Crossref PubMed Scopus (23) Google Scholar] reported that BCG and lung cancer cells shared common antigens, which could explain the false positivity observed for patients with lung cancer. We conclude that measurement of antibodies against A60, especially if molecular and new techniques for the diagnosis of tuberculosis are not available, may be considered a useful diagnostic tool in early active tuberculosis cases, as shown in a Turkish population. IgM antibody against A60 with high specificity could be used as a reliable test in the diagnosis of pulmonary tuberculosis when the result is positive.
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