Associations of Plasma Cytokine and Microbial Translocation Biomarkers With Immune Reconstitution Inflammatory Syndrome

George, Valérie; Harrison, Linda; Roach, Margaret; Li, Xiaodong; Tierney, Camlin; Fischl, Margaret A.; Aberg, Judith A.; Tebas, Pablo; Asmuth, David M.; Pollard, Richard B.; Godfrey, Catherine; Pahwa, Savita

doi:10.1093/infdis/jix460

Cited by 12 publications

(11 citation statements)

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“…Regarding TB-HIV co-infected individuals, there are few host factors associated with protection or susceptibility mechanisms. The immunological mechanisms underlying the development of IRIS are not yet clearly understood [4,37,64,65]. However, some authors have described potential biomarkers as predictors of IRIS development, for instance, interleukin-18 (IL-18) [4], CXCL10, and IFN-α2 [65].…”

Section: Discussionmentioning

confidence: 99%

“…The immunological mechanisms underlying the development of IRIS are not yet clearly understood [4,37,64,65]. However, some authors have described potential biomarkers as predictors of IRIS development, for instance, interleukin-18 (IL-18) [4], CXCL10, and IFN-α2 [65]. Similarly, Conesa-Botella et al reported that tumor necrosis factor (TNF), interferon-gamma (IFN-γ), IL-6, and IL-18 were significantly higher in patients with IRIS [66].…”

Section: Discussionmentioning

confidence: 99%

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Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

et al. 2020

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Background: Tuberculosis (TB) and AIDS are the leading causes of infectious disease death worldwide. In some TB-HIV co-infected individuals treated for both diseases simultaneously, a pathological inflammatory reaction termed immune reconstitution inflammatory syndrome (IRIS) may occur. The risk factors for IRIS are not fully defined. We investigated the association of HLA-B, HLA-C, and KIR genotypes with TB, HIV-1 infection, and IRIS onset. Methods: Patients were divided into four groups: Group 1-TB+/HIV+ (n = 88; 11 of them with IRIS), Group 2-HIV+ (n = 24), Group 3-TB+ (n = 24) and Group 4-healthy volunteers (n = 26). Patients were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. The HLA-B and HLA-C loci were typed using SBT, NGS, and KIR genes by PCR-SSP. Unconditional logistic regression models were performed for Protection/risk estimation. Results: Among the individuals with TB as the outcome, KIR2DS2 was associated with increased risk for TB onset (aOR = 2.39, P = 0.04), whereas HLA-B*08 and female gender were associated with protection against TB onset (aOR = 0.23, P = 0.03, and aOR = 0.33, P = 0.01, respectively). Not carrying KIR2DL3 (aOR = 0.18, P = 0.03) and carrying HLA-C*07 (aOR = 0.32, P = 0.04) were associated with protection against TB onset among HIV-infected patients. An increased risk for IRIS onset was associated with having a CD8 count ≤500 cells/mm 3 (aOR = 18.23, P = 0.016); carrying the KIR2DS2 gene (aOR = 27.22, P = 0.032), the HLA-B*41 allele (aOR = 68.84, P = 0.033), the KIR2DS1 + HLA-C2 pair (aOR = 28.58, P = 0.024); and not carrying the KIR2DL3 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), and the KIR2DL1 + HLA-C1/C2 pair (aOR = 43.04, P = 0.034), Conclusions: These results suggest the participation of these genes in the immunopathogenic mechanisms related to the conditions studied. This is the first study demonstrating an association of HLA-B*41, KIR2DS2, and KIR + HLA-C pairs with IRIS onset among TB-HIV co-infected individuals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

et al. 2020

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“…HIV targets subpopulations of CCR5-expressing CD4 + T cells, which are dense in the GI. Following this damage, microbial products translocate across the GI barrier and cause general activation of the immune system (9)(10)(11). In this context, it is noteworthy that HIV controller patients, who maintain high CD4 counts and good control of viremia, show low inflammation (12).…”

Section: Introductionmentioning

confidence: 99%

PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients

Pothlichet¹,

Rose²,

Bugault³

et al. 2020

Journal of Clinical Investigation

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“…Предполагается, что триггерным фактором развития СВИ является дисрегуляция иммунного ответа на воздействие антигенных стимулов на фоне начала АРВТ. Патофизиология процесса предполагает вовлечение нескольких факторов, таких как восстановление числа иммунокомпетентных клеток и функциональное перераспределение лимфоцитов, дефект в регуляторной функции, изменения Тhклеточного профиля, высокий уровень РНК ВИЧ, а также генетическая предрасположенность организма [32].…”

Section: патогенез свиunclassified

“…У пациентов с микобактериальным СВИ реже встречаются TNFα -308*2 и IL-6 -174*G. Эти аллели определяют низкую продукцию цитокинов. Наблюдения показали важную роль IL-12 в прогрессировании ЦМВ-СВИ, IL-6 и TNFα в развитии микобактериального СВИ [32,43]. Основные процессы формирования СВИ представлены на рисунке 1.…”

Section: патогенез свиunclassified

Immune Reconstitution Inflammatory Syndrome in Hiv Infection

Боева

Беляков

2018

Russian Journal of Infection and Immunity

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Antiretroviral therapy (ART) leads to suppression of HIV replication, contributes to increase in the number of CD4-lymphocytes count and partial restoration or activation of the immune system. The consequence is a reduction of incidence of opportunistic diseases, increase in the duration and quality of life of people living with HIV (PLHIV). However, in some patients with severe immunosuppression, this may be accompanied by a worsening of the condition and risks of formation of the immune reconstitution inflammatory syndrome (IRIS), which manifests itself in the development of new or previously treated opportunistic, secondary and exacerbating non- infectious diseases against a virologically effective ART. The frequency of the development of IRIS varies widely, in cases of tuberculosis-associated manifestation it can reach 50%. Risk factors for the development of IRIS are low initial CD4-lymphocyte count and a high load of HIV RNA in the blood, the presence of opportunistic infections during the initiation of ART. Discussed terminology issues, other possible risk factors for the development of the syndrome, regularities of the pathological process are considered. Epidemiological statistics of IRIS, pathogenetic bases, variants of clinical and laboratory manifestations of complications are given. The criteria for diagnosis of the syndrome, as well as the necessary conditions for its occurrence, are considered. Particular attention is paid to the most common opportunistic infections that cause the manifestation of IRIS, the peculiarities and polymorphism of clinical manifestations and the prevention of their occurrence. Currently, there is an increasing incidence of HIV infection in the late stages. Laboratory and clinical differences in the manifestations of acquired immunodeficiency syndrome (AIDS) and IRIS have been sanctified. In view of the blurring of the diagnostic criteria, in the Russian Federation specialists rarely expose IRIS to clinical or pathological diagnoses, therefore it is rather difficult to trace the frequency of occurrence of this condition. Clinical and laboratory manifestations are systematized, which allows to formulate this diagnosis on the basis of their totality. Prevention of IRIS is the prudent prescription of antiretroviral drugs. It is neces sary to conduct a qualitative and timely diagnosis of concomitant diseases of infectious and non-infectious nature before the initiation of ART and during treatment, the appointment of effective etiotropic therapy for opportunistic and secon dary infections. In order to improve the prognosis of HIV infection, preferably early onset of ART with stable CD4-lym phocyte counts and low HIV RNA levels in the blood.

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Associations of Plasma Cytokine and Microbial Translocation Biomarkers With Immune Reconstitution Inflammatory Syndrome

Cited by 12 publications

References 13 publications

Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients

Immune Reconstitution Inflammatory Syndrome in Hiv Infection

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