Determination of humoral immunoglobulins M and G directed against mycobacterial antigen 60 failed to diagnose primary tuberculosis and mycobacterial adenitis in children.

Abstract

The serodiagnosis of primary tuberculosis (TB) and mycobacterial adenitis in children was tried using the Anda-Tb tests (Anda Biologicals, France) that measure immunoglobulins (Ig) M and G directed against mycobacterial antigen 60 (A60) by enzyme-linked immunosorbent assay. The 188 cases studied included 81 healthy or mycobacteria-unrelated diseased children with no reaction to tuberculin skin test (STN); 9 recent BCG vaccination (BCG); 35 asymptomatic (AsTB), 29 symptomatic (STB) primary TB and 11 adenitis caused by atypical mycobacteria from the group avium-intracellulare-scrofulaceum (MAIS) tested before treatment; and 23 past primary TB tested at different times after completion of specific treatment (past TB). The individual IgM and IgG levels largely overlapped whatever the clinical status of the children. Setting the normal upper limit at the 95th percentile of the STN values, which by definition gives 95% specificity, the highest IgM sensitivity was found in past TB (35%), AsTB showing 23%, STB 17%, and MAIS 18% sensitivity. IgG sensitivity was also the highest in past TB (26%) and was equal to 6, 14, and 9% in AsTB, STB, and MAIS, respectively. Positive and negative predictive values and the test efficiency (63 and 62% for IgM and IgG, respectively) were far too low. Combining positivity for IgM and/or IgG did not improve the results. In our study, the anti-A60 IgM and IgG measurements using the Anda-Tb tests in primary TB and mycobacterial adenitis in children did not prove of any diagnostic help.

Antibody Responses to Mycobacterial Antigens in Children with Tuberculosis: Challenges and Potential Diagnostic Value

“…Overall, Ab responses to mycobacterial antigens in childhood TB varied widely, with sensitivities and specificities ranging from 14% to 85% and from 86% to 100%, respectively. Even when evaluating the same commercially available test, such as the Anda-TB Kit (Anda Biologicals, Strasbourg, France), sensitivities for detecting childhood TB ranged from 14% to 71% and specificities ranged from 50% to 100%, with part of the variability being due to the different isotypes tested (22,24,29,66,67) (Table 1). Such wide ranges in accuracy of serologic assays have also been observed in adult TB, although many of the reasons for this variability differ (reviewed in references 62 to 64).…”

“…Thus, similar to studies with PPD or mycobacterial sonicates, studies with A60-based assays evaluate serological responses to a broad mixture of mainly nonspecific native mycobacterial antigens, which may result in considerable cross-reactivity. Five studies have evaluated IgG, IgA, and IgM responses to A60 in children using the Anda-TB kit, with reported sensitivities ranging from 14% to 71% and specificities ranging from 50% to 100% (22,24,29,66,67) (Table 1).…”

“…Studies including IgM evaluation frequently also found higher levels of IgM than IgG. However, most of those studies indicated little diagnostic value of IgM due to considerable overlap between pediatric TB cases and controls (4,22,24,67). The overlap of IgM responses to mycobacterial antigens in TB cases and controls is likely to reflect the response to initial infection with mycobacteria, including environmental organisms, in early childhood, regardless of progression to disease.…”

Rapid Diagnosis of Active Tuberculosis by Detecting Antibodies from Lymphocyte Secretions

“…The introduction of these antigens has resulted in a much higher sensitivity and specificity in cell response assays [23]. However, serological tests based on mycobacterial antigens to detect circulating antibodies have been hampered by decreased sensitivity and cross-reactivity with other mycobacteria [24][25][26][27][28], or have relatively limited utility in the diagnosis of TB in countries where TB is endemic [29]. Several molecular biological techniques have been proposed as indicators of disease activity in pulmonary and extrapulmonary TB [30,31] and are currently the most sensitive and specific diagnostic tests.…”

Opportunities for Improved Serodiagnosis of Human Tuberculosis, Bovine Tuberculosis, and Paratuberculosis

“…Many studies have used this antigen and found almost 100% specificity [42], with sensitivity ranging from 68 to 91% [43, 85]. Unfortunately, this molecule has also been found in nonpathogenic Nocardia and Corynebacterium species [83].…”