Thymic Function as a Predictor of Immune Recovery in Chronically HIV-Infected Patients Initiating Antiretroviral Therapy

Frontiers in Immunology
Rita Rb-SilvaMargarida Correia-Neves

Abstract

Poor immunological responders (PIR) are HIV-infected patients with virologic suppression upon antiretroviral therapy (ART) but persistently low CD4+ T cell counts. Early identification of PIR is important given their higher morbimortality compared to adequate immune responders (AIR). In this study, 33 patients severely lymphopenic at ART onset, were followed for at least 36 months, and classified as PIR or AIR using cluster analysis grounded on their CD4+ T cell count trajectories. Based on a variety of immunological parameters, we built predictive models of PIR/AIR outcome using logistic regression. All PIR had CD4+ T cell counts consistently below 500 cells/μL, while all AIR reached this threshold. AIR showed a higher percentage of recent thymic emigrants among CD4+ T cells; higher numbers of sj-TRECs and greater sj/β TREC ratios; and significant increases in thymic volume from baseline to 12 months of ART. We identified mathematical models that correctly predicted PIR/AIR outcome after 36 months of therapy in 77-87% of the cases, based on observations made until 2-6 months after ART onset. This study highlights the importance of thymic activity in the immune recovery of severely lymphopenic patients, and may help to select t...Continue Reading

References

Nov 1, 1985·Scandinavian Journal of Immunology·G G SteinmannH K Müller-Hermelink
Jun 15, 1997·Annals of Internal Medicine·J W MellorsC R Rinaldo
Jun 17, 1998·The Journal of Clinical Investigation·J M McCuneR M Grant
Nov 28, 2001·JAMA : the Journal of the American Medical Association·R S HoggJ S Montaner
Oct 2, 2002·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Fernando DrondaAntonio Antela
Sep 15, 2004·The Journal of Experimental Medicine·Jason M BrenchleyDaniel C Douek
May 12, 2005·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Jeffrey M HarrisJoseph M McCune
Jul 12, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Gilbert R KaufmannUNKNOWN Swiss HIV Cohort Study
Aug 11, 2005·Current HIV/AIDS Reports·Rohan Hazra, Crystal Mackall
Apr 28, 2006·International Psychogeriatrics·Marie-Pierre SylvestreMichal Abrahamowicz
Jan 6, 2007·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Richard D Moore, Jeanne C Keruly
Sep 19, 2007·Methods in Molecular Biology·Marie-Lise DionRémi Cheynier
Dec 22, 2007·AIDS·Raphael Ho Tsong FangChristel H Uittenbogaart
Jan 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryan D KilpatrickBeth D Jamieson
Jun 28, 2008·Blood·Siegfried Kohler, Andreas Thiel
Jul 18, 2009·The Journal of Antimicrobial Chemotherapy·Sonia Molina-PineloManuel Leal
Oct 1, 2011·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Taisheng LiYanling Li
Nov 25, 2011·AIDS·Steven F L van LelyveldUNKNOWN ATHENA national observational cohort study
Mar 27, 2012·PLoS Medicine·UNKNOWN Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) Heiner Bucher
Mar 6, 2013·JAMA Internal Medicine·Matthew S FreibergAmy C Justice
Oct 11, 2013·Frontiers in Immunology·Donald B Palmer
Oct 31, 2013·Expert Review of Clinical Immunology·Marta MassanellaJulià Blanco
Jan 25, 2014·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Frederik N EngsigUNKNOWN Antiretroviral Therapy Cohort Collaboration (ART-CC) and the Collaboration of Observational HIV Epidemiological Research Eur

❮ Previous
Next ❯

Citations

Sep 3, 2019·AIDS Research and Human Retroviruses·Robert L FurlerDouglas F Nixon
Feb 28, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Christine KellySaye Khoo
Nov 7, 2019·Journal of Leukocyte Biology·Wlisses Henrique Veloso Carvalho-SilvaRafael Lima Guimarães
Sep 10, 2020·Frontiers in Immunology·Sinéad Kinsella, Jarrod A Dudakov
Mar 11, 2020·Frontiers in Cellular and Infection Microbiology·Tetsuo Tsukamoto
Aug 26, 2020·Environmental Health and Preventive Medicine·Mulugeta MelkuDegefaye Zelalem Anlay
Feb 21, 2021·Seminars in Immunopathology·David GranadierJarrod A Dudakov
Jan 24, 2021·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·C Serre-MirandaM Correia-Neves

❮ Previous
Next ❯

Methods Mentioned

BETA
Flow Cytometry
FACS
PCR

Software Mentioned

R
nlme
R traj package
R package traj
FlowJo
RStudio
FACS DIVA

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.