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 - 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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U2 - 10.1016/j.medj.2020.11.003
DO - 10.1016/j.medj.2020.11.003
M3 - Review article
C2 - 34693385
AN - SCOPUS:85122728384
SN - 2666-6359
VL - 2
SP - 217
EP - 232
JO - Med
JF - Med
IS - 3
ER -