Article
Cytokine responses and progression to active tuberculosis in HIV-1-infected Ugandans: a prospective study.
Uganda Virus Research Institute, P.O. Box 49, Entebbe, Uganda.
Transactions of the Royal Society of Tropical Medicine and Hygiene (impact factor:
2.16).
11/2004;
98(11):660-70.
DOI:10.1016/j.trstmh.2004.01.007
pp.660-70
Source: PubMed
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Citations (0)
- Cited In (10)
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Article: Immune restoration diseases reflect diverse immunopathological mechanisms.
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ABSTRACT: Up to one in four patients infected with human immunodeficiency virus type 1 and given antiretroviral therapy (ART) experiences inflammatory or cellular proliferative disease associated with a preexisting opportunistic infection, which may be subclinical. These immune restoration diseases (IRD) appear to result from the restoration of immunocompetence. IRD associated with intracellular pathogens are characterized by cellular immune responses and/or granulomatous inflammation. Mycobacterial and cryptococcal IRD are attributed to a pathological overproduction of Th1 cytokines. Clinicopathological characteristics of IRD associated with viral infections suggest different pathogenic mechanisms. For example, IRD associated with varicella-zoster virus or JC polyomavirus infection correlate with a CD8 T-cell response in the central nervous system. Exacerbations or de novo presentations of hepatitis associated with hepatitis C virus (HCV) infection following ART may also reflect restoration of pathogen-specific immune responses as titers of HCV-reactive antibodies rise in parallel with liver enzymes and plasma markers of T-cell activation. Correlations between immunological parameters assessed in longitudinal sample sets and clinical presentations are required to illuminate the diverse immunological scenarios described collectively as IRD. Here we present salient clinical features and review progress toward understanding their pathogeneses.Clinical microbiology reviews 10/2009; 22(4):651-63. · 14.69 Impact Factor -
Article: Endogenously activated interleukin-4 differentiates disease progressors and non-progressors in tuberculosis susceptible families: a 2-year biomarkers follow-up study.
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ABSTRACT: Dynamic cytokine profiles from endogenously activated T cells in transit from lymph node to the infected sites via the blood compartment after recent exposure to Mycobacterium tuberculosis may differentiate disease progressors from non-disease progressors in a BCG-vaccinated population. Household contacts (N = 107) from families with (six families) or without (14 families) secondary cases were assessed for Types 1 and 2 cytokines serially in plasma of whole blood cultures without exogenous stimulation. "ARMS" PCR was carried out for detection of single nucleotide polymorphism T/A in IFN-γ +874. In the absence of IFN-γ expansion, raised IL-4 at 6 months was associated with disease progression in TB-susceptible families. Resistant families on the other hand showed overrepresentation of IFN-γ +874 A allele and expansion of IFN-γ secreting cells at 6 months followed by contraction at 12 months. Six months may be an important checkpoint for biomarker assessment in high-risk individuals post-exposure.Journal of Clinical Immunology 07/2011; 31(5):913-23. · 3.08 Impact Factor -
Article: Predictive value of interferon-γ release assays for incident active tuberculosis: a systematic review and meta-analysis.
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ABSTRACT: We aimed to assess whether interferon-γ release assays (IGRAs) can predict the development of active tuberculosis and whether the predictive ability of these tests is better than that of the tuberculin skin test (TST). Longitudinal studies of the predictive value for active tuberculosis of in-house or commercial IGRAs were identified through searches of PubMed, Embase, Biosis, and Web of Science and complementary manual searches up to June 30, 2011. Eligible studies included adults or children, with or without HIV, who were free of active tuberculosis at study baseline. We summarised incidence rates in forest plots and pooled data with random-effects models when appropriate. We calculated incidence rate ratios (IRR) for rates of disease progression in IGRA-positive versus IGRA-negative individuals. 15 studies had a combined sample size of 26 680 participants. Incidence of tuberculosis during a median follow-up of 4 years (IQR 2-6), even in IGRA-positive individuals, was 4-48 cases per 1000 person-years. Seven studies with no possibility of incorporation bias and reporting baseline stratification on the basis of IGRA results showed a moderate association between positive results and subsequent tuberculosis (pooled unadjusted IRR 2·10, 95% CI 1·42-3·08). Compared with test-negative results, IGRA-positive and TST-positive results were much the same with regard to the risk of tuberculosis (pooled IRR in the five studies that used both was 2·11 [95% CI 1·29-3·46] for IGRA vs 1·60 [0·94-2·72] for TST at the 10 mm cutoff). However, the proportion of IGRA-positive individuals in seven of 11 studies that assessed both IGRAs and TST was generally lower than TST-positive individuals. Neither IGRAs nor the TST have high accuracy for the prediction of active tuberculosis, although use of IGRAs in some populations might reduce the number of people considered for preventive treatment. Until more predictive biomarkers are identified, existing tests for latent tuberculosis infection should be chosen on the basis of relative specificity in different populations, logistics, cost, and patients' preferences rather than on predictive ability alone. Special Programme for Research and Training in Tropical Diseases (WHO), Wellcome Trust, Canadian Institutes of Health Research, UK Medical Research Council, and the European and Developing Countries Clinical Trials Partnership.The Lancet Infectious Diseases 08/2011; 12(1):45-55. · 17.39 Impact Factor
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Keywords
631 HIV-1-infected Ugandan adults
culture filtrate proteins [CFP]
diagnostic tools
disease promotes understanding
expected role
Identifying correlates
IFN-gamma responses
IL-2 responses
interleukin [IL]-2
mycobacterial antigens
pathogenesis
positive IL-5 responses
purified protein derivative [PPD]
rate ratios [RR]
type 1
type 1 cytokine responses
type 2 cytokines
type 2 responses
type 2/immunosuppressive
whole blood cultures
