TY - JOUR
T1 - Tuberculosis endotypes to guide stratified host-directed therapy
AU - DiNardo, Andrew R.
AU - Nishiguchi, Tomoki
AU - Grimm, Sandra L.
AU - Schlesinger, Larry S.
AU - Graviss, Edward A.
AU - Cirillo, Jeffrey D.
AU - Coarfa, Cristian
AU - Mandalakas, Anna M.
AU - Heyckendorf, Jan
AU - Kaufmann, Stefan H.E.
AU - Lange, Christoph
AU - Netea, Mihai G.
AU - Van Crevel, Reinout
N1 - Funding Information:
A.R.D. is supported by National Institute of Allergy and Infectious Diseases (NIAID) grant K23 AI141681-02 . C.C. is supported by Cancer Prevention Institute of Texas (CPRIT) grant RP170005 , National Institutes of Health (NIH) P30 shared resource grant CA125123 , and National Institute of Environmental Health Sciences (NIEHS) grants 1P30ES030285 and 1P42ES0327725 . A.M.M. is supported by NIH /NIAID grant R01AI137527-01A1 and NIH /U.S. Department of Defense (DOD) grant W81XWH1910026. C.L. is funded by the German Center for Infection Research (DZIF). J.D.C. is supported in part by funds provided by the Texas A&M University System and NIH grant AI104960 . M.G.N. is supported by a European Research Council (ERC) Advanced Grant ( 833247 ) and a Spinoza grant from the Netherlands Organisation for Scientific Research . Figures were created using BioRender.
Funding Information:
A.R.D. is supported by National Institute of Allergy and Infectious Diseases (NIAID) grant K23 AI141681-02. C.C. is supported by Cancer Prevention Institute of Texas (CPRIT) grant RP170005, National Institutes of Health (NIH) P30 shared resource grant CA125123, and National Institute of Environmental Health Sciences (NIEHS) grants 1P30ES030285 and 1P42ES0327725. A.M.M. is supported by NIH/NIAID grant R01AI137527-01A1 and NIH/U.S. Department of Defense (DOD) grant W81XWH1910026. C.L. is funded by the German Center for Infection Research (DZIF). J.D.C. is supported in part by funds provided by the Texas A&M University System and NIH grant AI104960. M.G.N. is supported by a European Research Council (ERC) Advanced Grant (833247) and a Spinoza grant from the Netherlands Organisation for Scientific Research. Figures were created using BioRender.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/3/12
Y1 - 2021/3/12
N2 - There is hope that host-directed therapy (HDT) for tuberculosis (TB) can shorten treatment duration, help cure drug-resistant disease, or limit immunopathology. Many candidate HDT drugs have been proposed, but solid evidence only exists for a few select patient groups. The clinical presentation of TB is variable, with differences in severity, tissue pathology, and bacillary burden. TB clinical phenotypes likely determine the potential benefit of HDT. Underlying TB clinical phenotypes, there are TB “endotypes,” defined as distinct molecular profiles, with specific metabolic, epigenetic, transcriptional, and immune phenotypes. TB endotypes can be characterized by either immunodeficiency or pathologic excessive inflammation. Additional factors, such as comorbidities (HIV infection, diabetes, helminth infection), structural lung disease, or mycobacterial virulence also drive TB endotypes. Precise disease phenotyping, combined with in-depth immunologic and molecular profiling and multimodal omics integration, can identify TB endotypes, guide endotype-specific HDT, and improve TB outcomes, similar to advances in cancer medicine.
AB - There is hope that host-directed therapy (HDT) for tuberculosis (TB) can shorten treatment duration, help cure drug-resistant disease, or limit immunopathology. Many candidate HDT drugs have been proposed, but solid evidence only exists for a few select patient groups. The clinical presentation of TB is variable, with differences in severity, tissue pathology, and bacillary burden. TB clinical phenotypes likely determine the potential benefit of HDT. Underlying TB clinical phenotypes, there are TB “endotypes,” defined as distinct molecular profiles, with specific metabolic, epigenetic, transcriptional, and immune phenotypes. TB endotypes can be characterized by either immunodeficiency or pathologic excessive inflammation. Additional factors, such as comorbidities (HIV infection, diabetes, helminth infection), structural lung disease, or mycobacterial virulence also drive TB endotypes. Precise disease phenotyping, combined with in-depth immunologic and molecular profiling and multimodal omics integration, can identify TB endotypes, guide endotype-specific HDT, and improve TB outcomes, similar to advances in cancer medicine.
KW - endotypes
KW - immune correlates of protection
KW - tuberculosis
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UR - http://www.scopus.com/inward/citedby.url?scp=85122728384&partnerID=8YFLogxK
U2 - 10.1016/j.medj.2020.11.003
DO - 10.1016/j.medj.2020.11.003
M3 - Review article
C2 - 34693385
AN - SCOPUS:85122728384
VL - 2
SP - 217
EP - 232
JO - Med
JF - Med
SN - 2666-6359
IS - 3
ER -