Concurrent evaluation of cytokines improves the accuracy of antibodies against Mycobacterium tuberculosis antigens in the diagnosis of active tuberculosis
Ruschca Jacobs, Dolapo Olaitan Awoniyi, Ralf Baumann, Kim Stanley, Shirley McAnda, Susanne Kaempfer, Stephanus T. Malherbe, Mahavir Singh, Gerhard Walzl, Novel N. Chegou, Novel N. Chegou, Gerhard Walzl, Novel N. Chegou, Novel N. Chegou, Magdalena Kriel, Gian van der Spuy, André G. Loxton, Kim Stanley, Stephanus T. Malherbe, Belinda Kriel, Jayne S. Sutherland, Olumuyiwa Owolabi, Abdou K. Sillah, Joseph Mendy, Awa Gindeh, Simon Donkor, Toyin Togun, Martin O. C. Ota, Amelia C. Crampin, Felanji Simukonda, Alemayehu Amberbir, Femia Chilongo, Rein M G J Houben, Desta Kassa, Atsbeha Gebrezgeabher, Getnet Mesfin, Yohannes Belay, Gebremedhin Gebremichael, Yodit Alemayehu, Marieta van der Vyver, Faustina N. Amutenya, Josefina N. Nelongo, Lidia Monye, Jacob Sheehama, Scholastica Iipinge, Harriet Mayanja‐Kizza, Anna Ritah Namuganga, Grace Muzanye, Mary Nsereko, Pierre Peters, Rawleigh Howe, Adane Mihret, Yonas Bekele, Bamlak Tessema, Lawrence Yamuah, Tom H. M. Ottenhoff, Annemieke Geluk, Kees L. M. C. Franken, Jolien J. van der Ploeg-van Schip, Paul L. A. M. Corstjens, Elisa M. Tjon Kon Fat, Claudia J. de Dood, Ida Rosenkrands, Claus Aagaard, Stefan H. E. Kaufmann, Maria M. Esterhuyse, Jacqueline M. Cliff, Hazel M. Dockrell
Abstract
BACKGROUND: Antibodies against mycobacterial proteins are highly specific, but lack sensitivity, whereas cytokines have been shown to be sensitive but not very specific in the diagnosis of tuberculosis (TB). We assessed combinations between antibodies and cytokines for diagnosing TB. METHODS: Immuoglubulin (Ig) A and IgM antibody titres against selected mycobacterial antigens including Apa, NarL, Rv3019c, PstS1, LAM, "Kit 1" (MTP64 and Tpx)", and "Kit 2" (MPT64, Tpx and 19 kDa) were evaluated by ELISA in plasma samples obtained from individuals under clinical suspicion for TB. Combinations between the antibody titres and previously published cytokine responses in the same participants were assessed for diagnosing active TB. RESULTS: Antibody responses were more promising when used in combination (AUC of 0.80), when all seven antibodies were combined. When anti-"Kit 1"-IgA levels were combined with five host cytokine biomarkers, the AUC increased to 97% (92-100%) with a sensitivity of 95% (95% CI, 73-100%), and specificity of 88.5% (95% CI, 68.7-97%) achieved after leave-one-out cross validation. CONCLUSION: When used in combination, IgA titres measured with ELISA against multiple Mycobacterium tuberculosis antigens may be useful in the diagnosis of TB. However, diagnostic accuracy may be improved if the antibodies are used in combination with cytokines.