Abstract
BackgroundA previous study demonstrated pleural fluid (PF) IgA immunodominance for the fused MT10.3:MPT64 protein in pleural tuberculosis (PLTB) cases. However, no clue on the role of IgA and IgG against this and other antigens in PF and serum concerning improved diagnosis is available. Thus, the aim of the present study was to validate PF IgA-MT10.3:MPT64 and evaluate PF and serum IgA and IgG reactivity against this protein, its peptides (F2) and single MPT64, MT10.3 and the PPE59 mycobacterial specific antigens. IgA and IgG ELISA were measured against the antigen in PLTB (n = 29) and other non-TB pleurisy (n = 39) patient samples.ResultsThe immunodominance of PF IgA-MT10.3:MPT64 was confirmed in PLTB (86.2%) followed by PPE59 (62%), while serum IgA-F2 exhibited 51.7% sensitivity. PF and serum IgG-MT10.3:MPT64 led to 65.5 and 51.7% sensitivity, respectively. However, MT10.3 and MPT64 displayed overall lower sensitivity (≤34.5) for both antibodies. All results at 95% fixed specificity. Combinatory results indicated 93.1% sensitivity for PF IgA-MT10.3:MPT64/−PPE59 and IgA/IgG-MT10.3:MPT64 at 92.3% specificity, followed by IgA-MT10.3:MPT64/−MPT64 or /−F2 (89.6%) without jeopardizing specificity (94.9%). The combinatory results of the PF adenosine deaminase test (ADA) and IgA-MT10.3:MPT64/−F2 demonstrated the highest sensitivity (96.6%), with a specificity of 92.3%.ConclusionsThe PF IgA-MT10:MPT64 immune dominance was validated in PLTB, and its combinatory results with PPE59 or MPT64 or F2 antigens as well as with IgG, are reported herein for the first time, improving their potential to assist diagnosis. Combining PF-ADA and IgA-MT10.3:MPT64/−F2 results achieved better accuracy. Moreover, serum IgG, although less accurate, displays potential beyond microbiological tests.
Highlights
A previous study demonstrated pleural fluid (PF) immunoglobulin A (IgA) immunodominance for the fused MT10.3:MPT64 protein in pleural tuberculosis (PLTB) cases
As other non-tuberculous pleurisy (OPL) patients were older (p < 0.001) and the cancer pathology was dominant (64.1%), male gender was the majority of PLTB (72.5%), no significant difference compared to OPL was observed (p = 0.12)
The combinatory results for PF (1:50) IgA MT10.3:MPT64/−protein chimera MT10.3(1 M-40S) (F2) and adenosine deaminase test (ADA) displays a double advantage, as, besides increasing sensitivity (96.6%), the PF can be used at the same dilution for both fused Ags when compared to the combinatory results of different PF dilutions used to obtain the same high sensitivity, making them suitable as a diagnosis test to aid in PLTB diagnosis
Summary
A previous study demonstrated pleural fluid (PF) IgA immunodominance for the fused MT10.3:MPT64 protein in pleural tuberculosis (PLTB) cases. No clue on the role of IgA and IgG against this and other antigens in PF and serum concerning improved diagnosis is available. The aim of the present study was to validate PF IgA-MT10.3:MPT64 and evaluate PF and serum IgA and IgG reactivity against this protein, its peptides (F2) and single MPT64, MT10.3 and the PPE59 mycobacterial specific antigens. IgA and IgG ELISA were measured against the antigen in PLTB (n = 29) and other non-TB pleurisy (n = 39) patient samples. Among extrapulmonary presentations pleural tuberculosis (PLTB) is the most frequent in many countries, representing 15% of the extrapulmonary cases globally reported in 2016 [1,2,3].
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