Gender biased immune-biomarkers in active tuberculosis and correlation of their profiles to efficacy of therapy

Chavez, Karina; Ravindran, Resmi; Dehnad, Ali; Khan, Imran

doi:10.1016/j.tube.2016.03.009

Cited by 17 publications

(13 citation statements)

References 34 publications

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“…Indeed, the male subjects had higher viral load, lower CD4 cell count, and higher proportion sputum smear and Xpert MTB/RIF-positive results, albeit none of these findings were significant. Chavez et al [48] described different cytokine profiles between males and females with TB. It is possible that different biomarkers are optimal for TB screening in men and women.…”

Section: Discussionmentioning

confidence: 99%

Plasma Profiles of Inflammatory Markers Associated With Active Tuberculosis in Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Positive Individuals

Olssón

Björkman

Jansson

et al. 2019

Open Forum Infectious Diseases

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BackgroundDiagnosis of tuberculosis (TB) in human immunodeficiency virus (HIV)-coinfected individuals is challenging. We hypothesized that combinations of inflammatory markers could facilitate identification of active TB in HIV-positive individuals.MethodsParticipants were HIV-positive, treatment-naive adults systematically investigated for TB at Ethiopian health centers. Plasma samples from 130 subjects with TB (HIV+/TB+) and 130 subjects without TB (HIV+/TB−) were tested for concentration of the following markers: CCL5, C-reactive protein (CRP), interleukin (IL)-6, IL12-p70, IL-18, IL-27, interferon-γ-induced protein-10 (IP-10), procalcitonin (PCT), and soluble urokinase-type plasminogen activator receptor (suPAR). Analyzed markers were then assessed, either individually or in combination, with regard to infection status, CD4 cell count, and HIV ribonucleic acid (RNA) levels.ResultsThe HIV+/TB+ subjects had higher levels of all markers, except IL12p70, compared with HIV+/TB− subjects. The CRP showed the best performance for TB identification (median 27.9 vs 1.8 mg/L for HIV+/TB+ and HIV+/TB−, respectively; area under the curve [AUC]: 0.80). Performance was increased when CRP was combined with suPAR analysis (AUC, 0.83 [0.93 for subjects with CD4 cell count <200 cells/mm3]). Irrespective of TB status, IP-10 concentrations correlated with HIV RNA levels, and both IP-10 and IL-18 were inversely correlated to CD4 cell counts.ConclusionsAlthough CRP showed the best single marker discriminatory potential, combining CRP and suPAR analyses increased performance for TB identification.

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Section: Discussionmentioning

confidence: 99%

Plasma Profiles of Inflammatory Markers Associated With Active Tuberculosis in Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Positive Individuals

Olssón

Björkman

Jansson

et al. 2019

Open Forum Infectious Diseases

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“…It has been reported that Bacillus Calmette-Guerin (BCG) unvaccinated males display a stronger IFN-γ response against the tuberculin purified protein derivative (PPD) than females, which suggests that males display a stronger immune response that could be associated with an uncontrolled inflammatory response and a poor prognosis during M. tuberculosis infection [ 105 ]. During tuberculosis infection, there is also a differential immune response characterized by females showing higher levels of the C-X-C Motif Chemokine Ligand 9 (CXCL9) and males showing higher levels of the Platelet Derived Growth Factor Subunit B (PDGFB), serum C-reactive protein, and specific antibodies against M. tuberculosis than their gender counterpart, highlighting a stronger innate and humoral immune response in males [ 106 , 107 ]. Furthermore, the plasmatic levels of the anti-tuberculosis drugs, isoniazid, and pyrazinamide are lower in adult males than in females.…”

Section: Bacterial Infections In the Respiratory Tractmentioning

confidence: 99%

Sexual dimorphism in bacterial infections

et al. 2018

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BackgroundSex differences are important epidemiological factors that impact in the frequency and severity of infectious diseases. A clear sexual dimorphism in bacterial infections has been reported in both humans and animal models. Nevertheless, the molecular mechanisms involved in this gender bias are just starting to be elucidated. In the present article, we aim to review the available data in the literature that report bacterial infections presenting a clear sexual dimorphism, without considering behavioral and social factors.Main bodyThe sexual dimorphism in bacterial infections has been mainly attributed to the differential levels of sex hormones between males and females, as well as to genetic factors. In general, males are more susceptible to gastrointestinal and respiratory bacterial diseases and sepsis, while females are more susceptible to genitourinary tract bacterial infections. However, these incidences depend on the population evaluated, animal model and the bacterial species. Female protection against bacterial infections and the associated complications is assumed to be due to the pro-inflammatory effect of estradiol, while male susceptibility to those infections is associated with the testosterone-mediated immune suppression, probably via their specific receptors. Recent studies indicate that the protective effect of estradiol depends on the estrogen receptor subtype and the specific tissue compartment involved in the bacterial insult, suggesting that tissue-specific expression of particular sex steroid receptors contributes to the susceptibility to bacterial infections. Furthermore, this gender bias also depends on the effects of sex hormones on specific bacterial species. Finally, since a large number of genes related to immune functions are located on the X chromosome, X-linked mosaicism confers a highly polymorphic gene expression program that allows women to respond with a more expanded immune repertoire as compared with men.ConclusionNotwithstanding there is increasing evidence that confirms the sexual dimorphism in certain bacterial infections and the molecular mechanisms associated, further studies are required to clarify conflicting data and to determine the role of specific hormone receptors involved in the gender bias of bacterial infections, as well as their potential as therapeutic targets.

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“…Significant decreases in IP-10 are correlated with a good treatment response at month 2 17 , 18 and correlate with sputum conversion 19 and treatment outcome 20 . A pilot study in Nigeria and Nepal showed that the likelihood of culture positivity at diagnosis could be predicted through a change from high to low IP-10 plasma levels after seven days of treatment 21 .…”

Section: Introductionmentioning

confidence: 96%

IP-10 Kinetics in the First Week of Therapy are Strongly Associated with Bacteriological Confirmation of Tuberculosis Diagnosis in HIV-Infected Patients

García‐Basteiro

Mambuque

Hertog

et al. 2017

Sci Rep

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Simple effective tools to monitor the long treatment of tuberculosis (TB) are lacking. Easily measured host derived biomarkers have been identified but need to be validated in larger studies and different population groups. Here we investigate the early response in IP-10 levels (between day 0 and day 7 of TB therapy) to identify bacteriological status at diagnosis among 127 HIV-infected patients starting TB treatment. All participants were then classified as responding or not responding to treatment blindly using a previously described IP-10 kinetic algorithm. There were 77 bacteriologically confirmed cases and 41 Xpert MTB/RIF® and culture negative cases. Most participants had a measurable decline in IP-10 during the first 7 days of therapy. Bacteriologically confirmed cases were more likely to have high IP-10 levels at D0 and had a steeper decline than clinically diagnosed cases (mean decline difference 2231 pg/dl, 95% CI: 897–3566, p = 0.0013). Bacteriologically confirmed cases were more likely to have a measurable decline in IP-10 at day 7 than clinically diagnosed cases (48/77 (62.3%) vs 13/41 (31.7%), p < 0.001). This study confirms the association between a decrease in IP-10 levels during the first week of treatment and a bacteriological confirmation at diagnosis in a large cohort of HIV positive patients.

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Gender biased immune-biomarkers in active tuberculosis and correlation of their profiles to efficacy of therapy

Cited by 17 publications

References 34 publications

Plasma Profiles of Inflammatory Markers Associated With Active Tuberculosis in Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Positive Individuals

Plasma Profiles of Inflammatory Markers Associated With Active Tuberculosis in Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Positive Individuals

Sexual dimorphism in bacterial infections

IP-10 Kinetics in the First Week of Therapy are Strongly Associated with Bacteriological Confirmation of Tuberculosis Diagnosis in HIV-Infected Patients

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