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A Subgroup of Latently Mycobacterium tuberculosis Infected Individuals Is Characterized by Consistently Elevated IgA Responses to Several Mycobacterial Antigens.

Baumann R, Kaempfer S, Chegou NN, Oehlmann W, Spallek R, Loxton AG, van Helden PD, Black GF, Singh M, Walzl G - Mediators Inflamm. (2015)

Bottom Line: Studies in the field focussed mainly on IgG antibodies.Based on a specificity of 100%, anti-NarL IgA antibodies achieved with 78.6% sensitivity the highest accuracy for the detection of active TB compared to healthy controls.The novel antigen NarL may also be promising for the antibody-based diagnosis of active TB cases.

View Article: PubMed Central - PubMed

Affiliation: DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa ; Lionex Diagnostics and Therapeutics, Salzdahlumer Straße 196, 38126 Braunschweig, Germany.

ABSTRACT
Elevated antibody responses to Mycobacterium tuberculosis antigens in individuals with latent infection (LTBI) have previously been linked to an increased risk for progression to active disease. Studies in the field focussed mainly on IgG antibodies. In the present study, IgA and/or IgG responses to the mycobacterial protein antigens AlaDH, NarL, 19 kDa, PstS3, and MPT83 were determined in a blinded fashion in sera from 53 LTBI controls, 14 healthy controls, and 42 active TB subjects. Among controls, we found that elevated IgA levels against all investigated antigens were not randomly distributed but concentrated on a subgroup of <30%-with particular high levels in a small subgroup of ~5% comprising one progressor to active TB. Based on a specificity of 100%, anti-NarL IgA antibodies achieved with 78.6% sensitivity the highest accuracy for the detection of active TB compared to healthy controls. In conclusion, the consistently elevated IgA levels in a subgroup of controls suggest higher mycobacterial load, a risk factor for progression to active TB, and together with high IgG levels may have prognostic potential and should be investigated in future large scale studies. The novel antigen NarL may also be promising for the antibody-based diagnosis of active TB cases.

No MeSH data available.


Related in: MedlinePlus

Quality control SDS-PAGE analysis (reduced) of the highly purified recombinant antigens (1 μg per lane). Lane 1: PstS3, Lane 3: AlaDH, Lane 5: MPT83, Lane 7: 19 kDa, Lane 9: NarL, Lanes 2, 4, 6, 8, and 10: molecular weight ladders (each corresponding to the antigen on the left side), Lanes 1–4: 15% Laemmli gels, and Lanes 5–10: 12% Laemmli gels. All stained with Coomassie brilliant blue R250.
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fig1: Quality control SDS-PAGE analysis (reduced) of the highly purified recombinant antigens (1 μg per lane). Lane 1: PstS3, Lane 3: AlaDH, Lane 5: MPT83, Lane 7: 19 kDa, Lane 9: NarL, Lanes 2, 4, 6, 8, and 10: molecular weight ladders (each corresponding to the antigen on the left side), Lanes 1–4: 15% Laemmli gels, and Lanes 5–10: 12% Laemmli gels. All stained with Coomassie brilliant blue R250.

Mentions: The 5 protein antigens NarL, AlaDH, 19 kDa, PstS3, and MPT83 (Table 1) were cloned and expressed in E. coli and purified using standard chromatographic methods. A Coomassie Brilliant Blue R-250 stained SDS-PAGE analysis of the 5 proteins is shown in Figure 1.


A Subgroup of Latently Mycobacterium tuberculosis Infected Individuals Is Characterized by Consistently Elevated IgA Responses to Several Mycobacterial Antigens.

Baumann R, Kaempfer S, Chegou NN, Oehlmann W, Spallek R, Loxton AG, van Helden PD, Black GF, Singh M, Walzl G - Mediators Inflamm. (2015)

Quality control SDS-PAGE analysis (reduced) of the highly purified recombinant antigens (1 μg per lane). Lane 1: PstS3, Lane 3: AlaDH, Lane 5: MPT83, Lane 7: 19 kDa, Lane 9: NarL, Lanes 2, 4, 6, 8, and 10: molecular weight ladders (each corresponding to the antigen on the left side), Lanes 1–4: 15% Laemmli gels, and Lanes 5–10: 12% Laemmli gels. All stained with Coomassie brilliant blue R250.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4546975&req=5

fig1: Quality control SDS-PAGE analysis (reduced) of the highly purified recombinant antigens (1 μg per lane). Lane 1: PstS3, Lane 3: AlaDH, Lane 5: MPT83, Lane 7: 19 kDa, Lane 9: NarL, Lanes 2, 4, 6, 8, and 10: molecular weight ladders (each corresponding to the antigen on the left side), Lanes 1–4: 15% Laemmli gels, and Lanes 5–10: 12% Laemmli gels. All stained with Coomassie brilliant blue R250.
Mentions: The 5 protein antigens NarL, AlaDH, 19 kDa, PstS3, and MPT83 (Table 1) were cloned and expressed in E. coli and purified using standard chromatographic methods. A Coomassie Brilliant Blue R-250 stained SDS-PAGE analysis of the 5 proteins is shown in Figure 1.

Bottom Line: Studies in the field focussed mainly on IgG antibodies.Based on a specificity of 100%, anti-NarL IgA antibodies achieved with 78.6% sensitivity the highest accuracy for the detection of active TB compared to healthy controls.The novel antigen NarL may also be promising for the antibody-based diagnosis of active TB cases.

View Article: PubMed Central - PubMed

Affiliation: DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa ; Lionex Diagnostics and Therapeutics, Salzdahlumer Straße 196, 38126 Braunschweig, Germany.

ABSTRACT
Elevated antibody responses to Mycobacterium tuberculosis antigens in individuals with latent infection (LTBI) have previously been linked to an increased risk for progression to active disease. Studies in the field focussed mainly on IgG antibodies. In the present study, IgA and/or IgG responses to the mycobacterial protein antigens AlaDH, NarL, 19 kDa, PstS3, and MPT83 were determined in a blinded fashion in sera from 53 LTBI controls, 14 healthy controls, and 42 active TB subjects. Among controls, we found that elevated IgA levels against all investigated antigens were not randomly distributed but concentrated on a subgroup of <30%-with particular high levels in a small subgroup of ~5% comprising one progressor to active TB. Based on a specificity of 100%, anti-NarL IgA antibodies achieved with 78.6% sensitivity the highest accuracy for the detection of active TB compared to healthy controls. In conclusion, the consistently elevated IgA levels in a subgroup of controls suggest higher mycobacterial load, a risk factor for progression to active TB, and together with high IgG levels may have prognostic potential and should be investigated in future large scale studies. The novel antigen NarL may also be promising for the antibody-based diagnosis of active TB cases.

No MeSH data available.


Related in: MedlinePlus