Graves’ disease as immune reconstitution disease in HIV-positive patients is associated with naive and primary thymic emigrant CD4+ T-cell recovery

Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication of antiretroviral therapy (ART) in countries with high rates of endemic TB, but data from South-East Asia are incomplete. Identification of prevalence, risk factors and treatment outcomes of TB-IRIS in Malaysia was sought. Methods: A 3-year retrospective study was conducted among TB-HIV co-infected patients treated at the University of Malaya Medical Centre. Simple and adjusted logistic regressions were used to identify the predictors for TB-IRIS while Cox regression was used to assess the influence of TB-IRIS on long-term CD4 T-cell recovery. Results: One hundred and fifty-three TB-HIV patients were enrolled, of whom 106 had received both anti-TB treatment (ATT) and ART. The median (IQR) baseline CD4 T-cell count was 52 cells μL–1 (13–130 cells μL–1). Nine of 96 patients (9.4%) developed paradoxical TB-IRIS and eight developed unmasking TB-IRIS, at a median (IQR) time of 27 (12–64) and 19 (14–65) days, respectively. In adjusted logistic regression analysis, only disseminated TB was predictive of TB-IRIS [OR: 10.7 (95% CI: 1.2–94.3), P = 0.032]. Mortality rates were similar for TB-IRIS (n = 1, 5.9%) and non-TB-IRIS (n = 5, 5.7%) patients and CD4 T-cell recovery post-ART was not different between the two groups (P = 0.363). Conclusion: Disseminated TB was a strong independent predictor of TB-IRIS in Malaysian HIV-TB patients after commencing ART. This finding underscores the role of a high pathogen load in the pathogenesis of TB-IRIS; so interventions that reduce pathogen load before ART may benefit HIV patients with disseminated TB.

Download Full-text

IL18 gene polymorphism and its influence on CD4+ T-cell recovery in HIV-positive patients receiving antiretroviral therapy

Infection Genetics and Evolution ◽

10.1016/j.meegid.2019.103997 ◽

2019 ◽

Vol 75 ◽

pp. 103997 ◽

Cited By ~ 1

Author(s):

José Leandro Andrade-Santos ◽

Wlisses Henrique Veloso Carvalho-Silva ◽

Antonio Victor Campos Coelho ◽

Fabrício Oliveira Souto ◽

Sergio Crovella ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Gene Polymorphism ◽

Cd4 T Cell ◽

Hiv Positive ◽

Cell Recovery ◽

Il18 Gene Polymorphism ◽

Il18 Gene

Download Full-text

The effect of age on CD4+ T-cell recovery in HIV-suppressed adult participants: a sub-study from AIDS Clinical Trial Group (ACTG) A5321 and the Bone Loss and Immune Reconstitution (BLIR) study

Immunity & Ageing ◽

10.1186/s12979-021-00260-x ◽

2022 ◽

Vol 19 (1) ◽

Author(s):

Jingxian Chen ◽

Kehmia Titanji ◽

Anandi N. Sheth ◽

Rajesh Gandhi ◽

Deborah McMahon ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Count ◽

Immune Activation ◽

Immune Reconstitution ◽

Elimination Rate ◽

Older Age ◽

Cd4 T Cell ◽

Cell Recovery ◽

Cd4 T Cell Count

AbstractOlder age could be a risk factor for suboptimal CD4+ T-cell recovery in HIV-infected patients despite successful viral suppression. However, evaluation of this effect could be confounded by age-related immune processes such as decreased thymus output, increased immune activation and exhaustion. Here, we established a semi-mechanistic population model simultaneously describing naïve and memory CD4+ T-cell trajectories in 122 participants. Covariate analysis accounting for immune activation showed that older age was significantly associated with faster apparent elimination rate of the naïve T-cells. In addition, female sex predicted slower apparent elimination rate of memory T-cells. Simulations showed that the median maximal CD4+ T-cell count on ART treatment was 593 cells/μL (IQR 442-794) in patients aged 50 years or above and 738 cells/μL (IQR 548-1002) in patients aged 18-35 years. The differences in the percentage of subjects achieving sufficient immune reconstitution (CD4+ T-cell count> 500 cells/μL) between the two age groups were 15, 21 and 26% at year 1, 4 years and steady state, respectively, suggesting that advanced age may have a greater impact on long-term CD4+ T-cell recovery.

Download Full-text

Dynamics of HIV reservoir decay and naïve CD4 T-cell recovery between immune non-responders and complete responders on long-term antiretroviral treatment

Clinical Immunology ◽

10.1016/j.clim.2021.108773 ◽

2021 ◽

pp. 108773

Author(s):

Lu-Xue Zhang ◽

Jin-Wen Song ◽

Chao Zhang ◽

Xing Fan ◽

Hui-Huang Huang ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Treatment ◽

Cd4 T Cell ◽

Cell Recovery ◽

Hiv Reservoir

Download Full-text

European mitochondrial haplogroups are associated with CD4+ T cell recovery in HIV-infected patients on combination antiretroviral therapy

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkt206 ◽

2013 ◽

Vol 68 (10) ◽

pp. 2349-2357 ◽

Cited By ~ 11

Author(s):

María Guzmán-Fulgencio ◽

Juan Berenguer ◽

Dariela Micheloud ◽

Amanda Fernández-Rodríguez ◽

Mónica García-Álvarez ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Cd4 T Cell ◽

Combination Antiretroviral Therapy ◽

Cell Recovery ◽

Mitochondrial Haplogroups

Download Full-text

BANA-Positive Plaque Samples Are Associated with Oral Hygiene Practices and Not CD4+ T Cell Counts in HIV-Positive Patients

International Journal of Dentistry ◽

10.1155/2012/157641 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Cathy Nisha John ◽

Lawrence Xavier Graham Stephen ◽

Charlene Wilma Joyce Africa

Keyword(s):

T Cell ◽

Periodontal Disease ◽

Oral Hygiene ◽

Periodontal Diseases ◽

Cd4 T Cell ◽

Hiv Positive ◽

Hygiene Practices ◽

Cell Counts ◽

Probing Depth ◽

Clinical Indices

Background. The “red complex” microorganisms, namely,Porphyromonas gingivalis,Treponema denticola, andTannerella forsythiaare considered as potential pathogens causing HIV-associated periodontal diseases. Moreover, it has been recognized that an association exists between CD4+ T cell counts and periodontal disease progression.Objective. To establish whether CD4+ T cell counts or oral hygiene plays a greater role in producing BANA-positive results in HIV-associated periodontal disease.Materials and Methods. One hundred and twenty HIV-positive patients participated in the study, and their CD4+ T cell counts were obtained from their medical records. The six Ramfjord teeth were used for evaluating periodontal clinical indices and subgingival plaque sampling. BANA test was used for the detection and prevalence of the “red complex” bacteria in plaque samples.Results. A majority of 69.17% HIV-positive patients were BANA-positive. No significant associations were found between BANA and CD4+ T cell counts. A highly significant association was found between BANA with probing depth and clinical attachment level (P≤0.0001) and between BANA and the use of interdental aids (P=0.0168).Conclusion. HIV-associated periodontal diseases are strongly related to oral hygiene practices rather than the effect of CD4+ T cell counts, and the use of interdental aids was marked as a significant predictor of BANA-negative plaque samples.

Download Full-text

Interleukin-7 levels before highly active antiretroviral therapy may predict CD4+ T-cell recovery and virological failure in HIV-infected children

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkl032 ◽

2006 ◽

Vol 57 (4) ◽

pp. 798-800 ◽

Cited By ~ 8

Author(s):

Salvador Resino ◽

Alicia Pérez ◽

Juan Antonio León ◽

Mª Dolores Gurbindo ◽

Mª Ángeles Muñoz-Fernández

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Virological Failure ◽

Highly Active Antiretroviral Therapy ◽

Cd4 T Cell ◽

Cell Recovery ◽

Interleukin 7 ◽

Highly Active

Download Full-text

Activation-Induced CD4+ T Cell Death in HIV-Positive Individuals Correlates with Fas Susceptibility, CD4+ T Cell Count, and HIV Plasma Viral Copy Number

AIDS Research and Human Retroviruses ◽

10.1089/088922299309793 ◽

1999 ◽

Vol 15 (17) ◽

pp. 1509-1518 ◽

Cited By ~ 32

Author(s):

D. H. Dockrell ◽

A. D. Badley ◽

A. Algeciras-Schimnich ◽

M. Simpson ◽

R. Schut ◽

...

Keyword(s):

Cell Death ◽

T Cell ◽

Cell Count ◽

Copy Number ◽

Cd4 T Cell ◽

Hiv Positive ◽

Viral Copy Number ◽

Viral Copy ◽

Cd4 T Cell Count

Download Full-text

Dynamical Systems Modeling of Early-Term Immune Reconstitution with Different Anti-Thymocyte Globulin (ATG) Administration Schedules in Allogeneic Stem Cell Transplantation.

10.1101/2021.05.21.21257336 ◽

2021 ◽

Author(s):

Viktoriya Zelikson ◽

Amir Ahmed Toor ◽

Gary Simmons ◽

Natasha Raman ◽

Elizabeth Krieger ◽

...

Keyword(s):

T Cell ◽

Clinical Outcomes ◽

Cell Transplantation ◽

Immune Reconstitution ◽

Cellular Therapy ◽

Immune Cell ◽

Chronic Gvhd ◽

T Cell Response ◽

Cell Recovery ◽

Early Term

Alloreactivity forms the basis of allogeneic hematopoietic cell transplantation (HCT), with donor derived T cell response to recipient antigens mediating clinical responses either in part or entirely. These encompass the different manifestations of graft vs. host disease (GVHD), infection risk as well as disease response. Whilst the latter is contingent upon disease biology and thus may be less predictable, the former two are more likely to be directly proportional to the magnitude of donor derived T cell recovery. Herein we explore the quantitative aspects of immune cell recovery following allogeneic HCT and clinical outcomes in two cohorts of HLA matched allograft recipients who received rabbit anti-thymocyte globulin (ATG) on different schedules (days -9 to -7 vs. -3 to -1). Monocyte as well as donor derived T cell (ddCD3) recovery was superior in those given ATG early in their course (days -9/-7). This difference was related to a more rapid rate of ddCD3 recovery, largely driven by CD3+/8+ cells in the first month following transplantation. Early monocyte recovery was associated with later T cell recovery, improved survival, and less chronic GVHD. In contrast rapid and early ddCD3 expansion out of proportion to monocyte recovery was associated with a high likelihood of acute GVHD and poor survival. This analytic methodology demonstrates that modeling 'early-term immune reconstitution' following HCT yields insights that may be useful in management of post-transplant immunosuppression and adaptive cellular therapy to optimize clinical outcomes.

Download Full-text

Immune Reconstitution After Gene Therapy Approaches in Patients With X-Linked Severe Combined Immunodeficiency Disease

Frontiers in Immunology ◽

10.3389/fimmu.2020.608653 ◽

2020 ◽

Vol 11 ◽

Author(s):

Elena Blanco ◽

Natalia Izotova ◽

Claire Booth ◽

Adrian James Thrasher

Keyword(s):

Gene Therapy ◽

T Cell ◽

Nk Cells ◽

Immune Reconstitution ◽

Lymphoblastic Leukemia ◽

Conditioning Regimen ◽

Cell Recovery ◽

Hematopoietic Stem ◽

Conditioning Treatment ◽

Immunodeficiency Disease

X-linked severe immunodeficiency disease (SCID-X1) is an inherited, rare, and life-threating disease. The genetic origin is a defect in the interleukin 2 receptor γ chain (IL2RG) gene and patients are classically characterized by absence of T and NK cells, as well as presence of partially-functional B cells. Without any treatment the disease is usually lethal during the first year of life. The treatment of choice for these patients is hematopoietic stem cell transplantation, with an excellent survival rate (>90%) if an HLA-matched sibling donor is available. However, when alternative donors are used, the success and survival rates are often lower. Gene therapy has been developed as an alternative treatment initially using γ-retroviral vectors to correct the defective γ chain in the absence of pre-conditioning treatment. The results were highly promising in SCID-X1 infants, showing long-term T-cell recovery and clinical benefit, although NK and B cell recovery was less robust. However, some infants developed T-cell acute lymphoblastic leukemia after the gene therapy, due to vector-mediated insertional mutagenesis. Consequently, considerable efforts have been made to develop safer vectors. The most recent clinical trials using lentiviral vectors together with a low-dose pre-conditioning regimen have demonstrated excellent sustained T cell recovery, but also B and NK cells, in both children and adults. This review provides an overview about the different gene therapy approaches used over the last 20 years to treat SCID-X1 patients, particularly focusing on lymphoid immune reconstitution, as well as the developments that have improved the process and outcomes.

Download Full-text