Inflammatory biomarkers of asymptomatic and symptomatic tuberculosis
Abstract
Abstract A large proportion of individuals with tuberculosis (TB) are asymptomatic. The biological and inflammatory underpinnings of asymptomatic TB are unknown and may differ from symptomatic TB. We characterise blood transcriptomic and proteomic profiles in South African community screening vs. health facility-based triage cohorts. Asymptomatic TB shares core transcriptomic and proteomic features with symptomatic TB, including upregulation of innate, interferon and inflammatory pathways and downregulation of T and B cell pathways. Integration of transcriptomic and proteomic data from asymptomatic TB individuals identifies two distinct sub-clusters characterized by higher or lower bacterial burden, blood IFN-γ responses, BMI, and chest radiographic abnormalities, suggesting different disease severity. We identify a new blood transcriptomic signature of asymptomatic TB. However, diagnostic performance of transcriptomic and proteomic markers is weaker for asymptomatic TB than symptomatic TB, suggesting that policy development for community-based, asymptomatic TB screening should not adopt biomarkers developed for symptomatic TB triage without further optimization.
Article Details
Authors (233)
Denis Awany
Dominique T. Ariefdien
Simon C. Mendelsohn
Virginie Rozot
Humphrey Mulenga
Sarah Nyangu
Michele Tameris
Tumelo Moloantoa
Austin Katona
Fernanda Maruri
Firdows Noor
Ravindre Panchia
Khuthadzo Hlongwane
Kim Stanley
Yuri F. van der Heijden
Katie Hadley
Andrew- Fiore Gartland
Craig Innes
William Brumskine
Keertan Dheda
Shameem Jaumdally
Tahlia Perumal
Neil Martinson
Al Leslie
Bernard Fourie
Stephanus T. Malherbe
Gerhard Walzl
Kogieleum Naidoo
Gavin Churchyard
Novel N. Chegou
Timothy R. Sterling
Mark Hatherill
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, University of Cape Town, Cape Town, South Africa
Thomas J. Scriba
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Pathology, University of Cape Town, Cape Town, South Africa
Pattamukkil Abraham
Thakiera Allie
Cynthia Baard
Zainab Baig
John Belisle
Nicole Bilek
Gerard Cangelosi
Ace Carstens
Kevyna Chetty
Yolundi Cloete
Marwou de Kock
Gareta Dickman
Charity Dire
Karen Dobos
Stephany Norah Duda
Mzwandile Erasmus
Marina Cruvinel Figueiredo
Marika Flinn
Travis Harris
Ryan Johnson
Farina Karim
Masooda Kaskar
Nobulumko Khomba
Thandeka Khoza
Léanie Kleynhans
Tahira Kootbodien
Andrea Kotze
Belinda A. Kriel
Ané Kruger
Lorraine Lichakane
Ilze Louw
Angelique Luabeya
Candice Macdonald
Lindiwe Madziwa
Lebohang Makhethe
Sandisiwe Mangali
Linda Mbuthini
Carolina Mehaffy
Thabang Moloja
Angelique Mouton
Evans Muchiri
Mbusiseni Ngema
Hlengiwe Nkambule
Onke Nombida
Alaina Olson
Fajwa Opperman
Gregory Ording-Jespersen
Kennedy Otwombe
Will Ramsay
Tracy Richardson
Carmen Segelaar
Jane Shaw
Kimberly Shelton
Justin Shenje
Theresa Smit
Bronwyn Smith
Candice Snyders
Marcia Steyn
Sara Suliman
Floris Swanepoel
Lorraine Thobakgale
Susanne Tönsing
Nicolette Tredoux
Megan Turner
Petrus Tyambetyuv
Habibullah Valley
Lyle van de Berg
Gian van der Spuy
Ilana R. van Rensburg
Johanna E. van Rooyen
Hilary Vansell Riley
Ashley Veldsman
Lindsay Wilson
Rachel C. Wood
Lesley Workman
Heather Zar
Charmaine Abrahams
Hadn Africa
Petri Ahlers
Laudicia Tshenolo Bontsi
Obakeng Peter Booi
Natasja Botes
Mari Cathrin Botha
Samentra Braaf
Sivuyile Buhlungu
Alida Carstens
Nompumelelo Cetywayo
Kgomotso Violet Chauke
Tilagavathy Chinappa
Eva Chung
Michelle Chung
Alessandro Companie
Cara-Mia Corris
Mooketsi Theophillius Cwaile
Thobelani Cwele
Ilse Davids
Isabella Johanna Davies
Emilia De Klerk
Bongani Diamond
Celaphiwe Dlamini
Margareth Erasmus
Elizabeth Filander
Hennie Geldenhuys
Dhineshree Govender
Yolande Gregg
Goodness Khanyisile Gumede
Nonhlanhla Zanele Elsie Gwamanda
Roxane Herling
Andriëtte Hiemstra
Senzo Ralph Hlathi
Blanchard Mbay Iyemosolo
Zandile Patrica Jali
Ruwiyda Jansen
James Michael Jeleni
Fazlin Kafaar
Christian Mabika Kasongo
Sebaetseng Jeanette Kekana
Xoliswa Kelepu
Justine Khoury
Lucky Sipho Khoza
Gloria Keitumetse Kolobe
Belinda Kriel
Lerato Julia Lekagane
Sheiley Christina Lekotloane
Ilze Jeanette Louw
Andre Loxton
Sarah Teboso Lusale
Elizna Maasdorp
Perfect Tiisetso Maatjie
Kamogelo Fortunate Mabena
Simbarashe Mabwe
Lauren Mactavie
Johanna Thapelo Madikwe
Octavia Mahkosazana Madikwev
Rapontwana Letlhogonolo Maebana
Nomsitho Magawu
Malobisa Sylvester Magwasha
Bhavna Maharaj
Lebohgang Makhete
Vutlhari-I-Vunhenha Fairlord Manzini
Nonhle Bridgette Maphanga
Jabulisiwe Lethabo Maphanga
Isholedi Samuel Maroele
Omphile Petunia Masibi
July Rocky Mathabanzini
Tendamudzimu Ivan Mathode
Ellen Ditaba Matsane
Lungile Mbata
Siyabonga Mbatha
Nyasha Karen Mhandire
Thembisiwe Miga
Nosisa Charity Thandeka Mkhize
Caroline Mkhokho
Neo Hilda Mkwalase
Nondzakazi Mnqonywa
Brenda Matshidiso Modisaotsile
Patricia Pakiso Mokgetsengoane
Selemeng Matseliso Carol Mokone
Kegomoditswe Magdeline Molatlhegi
Thuso Andrew Molefe
Motlatsi Evelyn Molotsi
Tebogo Edwin Montwedi
Boikanyo Dinah Monyemangene
Hellen Mokopi Mooketsi
Atika Moosa
Razia Hassan Moosa
Miriam Moses
Tshplpfelo Mapula Mosito
Ireen Lesebang Mosweu
Banyana Olga Motlagomang
Funeka Nomvula Mthembu
Liesel Muller
Nambitha Nqakala
Ntombozuko Gloria Ntanjana
Sphelele Simo Nzimande
Christel Petersen
Themba Phakathi
Mapule Ozma Phatshwane
Patiswa Plaatjie
Victor Kgothatso Rameetse
Frances Ratangee
Susan Rossouw
Alicia Sato
Kelebogile Magdeline Segaetsho
Ni Ni Sein
Melissa Neo Senne
Sifiso Cornelius Shezi
Thandiwe Yvonne Shezi
Zibuyile Phindile Penlee Sing
Zona Sithetho
Bongiwe Stofile
Sonia Stryers
Liticia Swanepoel
Mando Mmakhora Thaba
Lethabo Collen Theko
Dimakatso Sylvia Tsagae
Petrus Tyambetyu
Elma Van Rooyen
Helen Veldtsman
Mbali Ignatia Zulu