A Subgroup of Latently Mycobacterium tuberculosis Infected Individuals Is Characterized by Consistently Elevated IgA Responses to Several Mycobacterial Antigens.
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.
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.
Ralf
R
Baumann
Lionex Diagnostics and Therapeutics, Salzdahlumer Straße 196, 38126 Braunschweig, Germany.
Susanne
S
Kaempfer
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.
Novel N
NN
Chegou
Lionex Diagnostics and Therapeutics, Salzdahlumer Straße 196, 38126 Braunschweig, Germany.
Wulf
W
Oehlmann
Lionex Diagnostics and Therapeutics, Salzdahlumer Straße 196, 38126 Braunschweig, Germany.
Ralf
R
Spallek
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.
André G
AG
Loxton
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.
Paul D
PD
van Helden
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.
Gillian F
GF
Black
Lionex Diagnostics and Therapeutics, Salzdahlumer Straße 196, 38126 Braunschweig, Germany.
Mahavir
M
Singh
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.
Gerhard
G
Walzl
D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012189:Retrospective Studies; D055815:Young Adult
D000942:Antigens, Bacterial; D007070:Immunoglobulin A