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Specific in vitro interferon-gamma and IL-2 production as biomarkers during treatment of chronic Q fever.

Schoffelen T, Wegdam-Blans MC, Ammerdorffer A, Pronk MJ, Soethoudt YE, Netea MG, van der Meer JW, Bleeker-Rovers CP, van Deuren M - Front Microbiol (2015)

Bottom Line: Treatment was considered successful when clinical recovery was observed, a positive PCR for C. burnetii DNA in blood became persistently negative, anti-phase I IgG showed a fourfold decrease or more, and imaging techniques showed disappearance of infectious foci.Overall, the IFN-γ/IL-2 ratio declined when patients experienced a successful treatment outcome.When treatment failed, IFN-γ/IL-2 ratios did not significantly decrease.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands.

ABSTRACT

Background: Antibiotic treatment of chronic Q fever is cumbersome and of long duration. To monitor treatment, there is a need for alternative biomarkers. Coxiella burnetii-specific interferon (IFN)-γ and interleukin (IL)-2 production reflect the type of effector and memory T-cell response. In chronic Q fever, C. burnetii-specific IFN-γ production is higher and IL-2 production is lower than in individuals with past Q fever. Here we explore whether C. burnetii-specific IFN-γ and IL-2 production correlate to treatment response.

Methods: We studied the longitudinal C. burnetii-specific IFN-γ/IL-2 ratio in fifteen proven chronic Q fever patients. All patients were followed for at least 18 months during antibiotic treatment. Treatment was considered successful when clinical recovery was observed, a positive PCR for C. burnetii DNA in blood became persistently negative, anti-phase I IgG showed a fourfold decrease or more, and imaging techniques showed disappearance of infectious foci.

Results: Overall, the IFN-γ/IL-2 ratio declined when patients experienced a successful treatment outcome. When treatment failed, IFN-γ/IL-2 ratios did not significantly decrease. The median (±IQR) slope of the longitudinal IFN-γ/IL-2 ratio with successful treatment was -2.10 (-7.02 to -0.06), and -0.15 (-1.13 to 0.25) with unsuccessful treatment (P = 0.19). Q fever endocarditis patients had higher IFN-γ/IL-2 ratios than patients with endovascular infections.

Conclusion: We propose that the IFN-γ/IL-2 ratio can be used as an additional biomarker for monitoring chronic Q fever treatment, with declining ratios being indicative of successful treatment.

No MeSH data available.


Related in: MedlinePlus

Non-linear regression to straight curves of the longitudinal IFN-γ/IL-2 ratios of chronic Q fever patients. Patients with successful treatment are shown in green, patients with unsuccessful treatment are shown in red. The median (±IQR) slope of the patients with successful treatment was -2.10 (-7.02 to -0.06), compared to -0.15 (-1.13 to 0.25) in patients with unsuccessful treatment (P = 0.19).
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Figure 3: Non-linear regression to straight curves of the longitudinal IFN-γ/IL-2 ratios of chronic Q fever patients. Patients with successful treatment are shown in green, patients with unsuccessful treatment are shown in red. The median (±IQR) slope of the patients with successful treatment was -2.10 (-7.02 to -0.06), compared to -0.15 (-1.13 to 0.25) in patients with unsuccessful treatment (P = 0.19).

Mentions: We studied the longitudinal IFN-γ/IL-2 ratio in fifteen chronic Q fever patients (Table 1). All were followed for at least 18 months during antibiotic treatment. In some cases, this included a period after completion of the treatment. For the purpose of this study, the data of all patients were analyzed according to start of antimicrobial therapy (t = 0), which was up to 35 months before inclusion. We divided the group in patients with successful treatment (n = 8) and those with unsuccessful treatment (n = 7; Figure 2). The latter group did not fulfill the success-criteria because of persistent PCR positivity for C. burnetii in blood (patient 9), less than a fourfold decrease in anti-phase I IgG titer (patient 3, 8, 11, 14), and/or persistent uptake on FDG-PET/CT (patient 3, 6, 7, 8, 14). As can be seen in Figure 2, the patients with successful treatment had higher maximum IFN-γ/IL-2 ratios than those with unsuccessful treatment. Moreover, the IFN-γ/IL-2 ratio of the patients with successful treatment showed a more pronounced decrease, each with an individual pattern, compared to the patients with unsuccessful treatment. We performed non-linear regression of the longitudinal IFN-γ/IL-2 ratios of each patient to a best-fit straight line (Figure 3). The median (±IQR) slope of the patients with successful treatment was -2.10 (-7.02 to -0.06), compared to -0.15 (-1.13 to 0.25) in patients with unsuccessful treatment (P = 0.19). Because the two main clinical manifestations of chronic Q fever may differ immunologically, the patients with endocarditis were also depicted separately from the patients with vascular (prosthesis) infection (Figure 4). Q fever endocarditis patients had overall higher IFN-γ/IL-2 ratios than the vascular Q fever patients.


Specific in vitro interferon-gamma and IL-2 production as biomarkers during treatment of chronic Q fever.

Schoffelen T, Wegdam-Blans MC, Ammerdorffer A, Pronk MJ, Soethoudt YE, Netea MG, van der Meer JW, Bleeker-Rovers CP, van Deuren M - Front Microbiol (2015)

Non-linear regression to straight curves of the longitudinal IFN-γ/IL-2 ratios of chronic Q fever patients. Patients with successful treatment are shown in green, patients with unsuccessful treatment are shown in red. The median (±IQR) slope of the patients with successful treatment was -2.10 (-7.02 to -0.06), compared to -0.15 (-1.13 to 0.25) in patients with unsuccessful treatment (P = 0.19).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325914&req=5

Figure 3: Non-linear regression to straight curves of the longitudinal IFN-γ/IL-2 ratios of chronic Q fever patients. Patients with successful treatment are shown in green, patients with unsuccessful treatment are shown in red. The median (±IQR) slope of the patients with successful treatment was -2.10 (-7.02 to -0.06), compared to -0.15 (-1.13 to 0.25) in patients with unsuccessful treatment (P = 0.19).
Mentions: We studied the longitudinal IFN-γ/IL-2 ratio in fifteen chronic Q fever patients (Table 1). All were followed for at least 18 months during antibiotic treatment. In some cases, this included a period after completion of the treatment. For the purpose of this study, the data of all patients were analyzed according to start of antimicrobial therapy (t = 0), which was up to 35 months before inclusion. We divided the group in patients with successful treatment (n = 8) and those with unsuccessful treatment (n = 7; Figure 2). The latter group did not fulfill the success-criteria because of persistent PCR positivity for C. burnetii in blood (patient 9), less than a fourfold decrease in anti-phase I IgG titer (patient 3, 8, 11, 14), and/or persistent uptake on FDG-PET/CT (patient 3, 6, 7, 8, 14). As can be seen in Figure 2, the patients with successful treatment had higher maximum IFN-γ/IL-2 ratios than those with unsuccessful treatment. Moreover, the IFN-γ/IL-2 ratio of the patients with successful treatment showed a more pronounced decrease, each with an individual pattern, compared to the patients with unsuccessful treatment. We performed non-linear regression of the longitudinal IFN-γ/IL-2 ratios of each patient to a best-fit straight line (Figure 3). The median (±IQR) slope of the patients with successful treatment was -2.10 (-7.02 to -0.06), compared to -0.15 (-1.13 to 0.25) in patients with unsuccessful treatment (P = 0.19). Because the two main clinical manifestations of chronic Q fever may differ immunologically, the patients with endocarditis were also depicted separately from the patients with vascular (prosthesis) infection (Figure 4). Q fever endocarditis patients had overall higher IFN-γ/IL-2 ratios than the vascular Q fever patients.

Bottom Line: Treatment was considered successful when clinical recovery was observed, a positive PCR for C. burnetii DNA in blood became persistently negative, anti-phase I IgG showed a fourfold decrease or more, and imaging techniques showed disappearance of infectious foci.Overall, the IFN-γ/IL-2 ratio declined when patients experienced a successful treatment outcome.When treatment failed, IFN-γ/IL-2 ratios did not significantly decrease.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Radboud University Medical Center Nijmegen, Netherlands.

ABSTRACT

Background: Antibiotic treatment of chronic Q fever is cumbersome and of long duration. To monitor treatment, there is a need for alternative biomarkers. Coxiella burnetii-specific interferon (IFN)-γ and interleukin (IL)-2 production reflect the type of effector and memory T-cell response. In chronic Q fever, C. burnetii-specific IFN-γ production is higher and IL-2 production is lower than in individuals with past Q fever. Here we explore whether C. burnetii-specific IFN-γ and IL-2 production correlate to treatment response.

Methods: We studied the longitudinal C. burnetii-specific IFN-γ/IL-2 ratio in fifteen proven chronic Q fever patients. All patients were followed for at least 18 months during antibiotic treatment. Treatment was considered successful when clinical recovery was observed, a positive PCR for C. burnetii DNA in blood became persistently negative, anti-phase I IgG showed a fourfold decrease or more, and imaging techniques showed disappearance of infectious foci.

Results: Overall, the IFN-γ/IL-2 ratio declined when patients experienced a successful treatment outcome. When treatment failed, IFN-γ/IL-2 ratios did not significantly decrease. The median (±IQR) slope of the longitudinal IFN-γ/IL-2 ratio with successful treatment was -2.10 (-7.02 to -0.06), and -0.15 (-1.13 to 0.25) with unsuccessful treatment (P = 0.19). Q fever endocarditis patients had higher IFN-γ/IL-2 ratios than patients with endovascular infections.

Conclusion: We propose that the IFN-γ/IL-2 ratio can be used as an additional biomarker for monitoring chronic Q fever treatment, with declining ratios being indicative of successful treatment.

No MeSH data available.


Related in: MedlinePlus