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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

Detailed overview of immunological parameters in (A) patient 1 (B) patient 2, and (C) patient 3 from start of antibiotic treatment to end of study follow-up. The IFN-γ and IL-2 concentrations (dotted lines) and the IFN-γ/IL-2 ratio (black diamant) are shown on the left y-axis, the anti-phase I IgG antibody-titer (black triangle) is shown on the right y-axis. The course of antibiotic treatment is depicted above each graph.
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Figure 1: Detailed overview of immunological parameters in (A) patient 1 (B) patient 2, and (C) patient 3 from start of antibiotic treatment to end of study follow-up. The IFN-γ and IL-2 concentrations (dotted lines) and the IFN-γ/IL-2 ratio (black diamant) are shown on the left y-axis, the anti-phase I IgG antibody-titer (black triangle) is shown on the right y-axis. The course of antibiotic treatment is depicted above each graph.

Mentions: A 30-years-old man with a medical history of traumatic rupture of the thoracic aorta, for which he had undergone vascular surgery receiving an endoprosthesis, suffered from new symptoms of malaise, night sweats, weight loss, and chills. Because of the preceding Q fever epidemic, serology for C. burnetii was performed, revealing chronic infection with very high IgG titers against phase I and II (both 1:65536). PCR on serum for C. burnetii DNA was positive. He was not aware of a preceding acute Q fever episode. FDG-PET/CT showed no signs of infection at the thoracic aortic prosthesis, nor elsewhere. Transesophageal echocardiogram (TEE) showed mild aortic valve insufficiency without vegetations. Although infection of the vascular prosthesis could not be detected with FDG-PET/CT, it was considered the most likely focus of infection. The patient started antimicrobial therapy with doxycycline and hydroxychloroquine after which he made a quick clinical recovery. PCR in serum became permanently negative 5 months after start of therapy. Although anti-phase I IgG titers had decreased from 1:131072 to 1:8192 in 24 months, titers did not decrease further and moxifloxacin was added to the therapy. This regimen was continued for another 14 months, after which it was decided to stop treatment and continue follow-up 3-monthly. The follow-up –6 months so far– was uneventful. This patient, having a good response on the antimicrobial therapy, showed peaking of the IFN-γ/IL-2 ratio during the first 9 months. Thereafter, the ratio declined and was stable at lower values during the last phase of the treatment, analog to the anti-phase I antibody titers (Figure 1A).


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)

Detailed overview of immunological parameters in (A) patient 1 (B) patient 2, and (C) patient 3 from start of antibiotic treatment to end of study follow-up. The IFN-γ and IL-2 concentrations (dotted lines) and the IFN-γ/IL-2 ratio (black diamant) are shown on the left y-axis, the anti-phase I IgG antibody-titer (black triangle) is shown on the right y-axis. The course of antibiotic treatment is depicted above each graph.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Detailed overview of immunological parameters in (A) patient 1 (B) patient 2, and (C) patient 3 from start of antibiotic treatment to end of study follow-up. The IFN-γ and IL-2 concentrations (dotted lines) and the IFN-γ/IL-2 ratio (black diamant) are shown on the left y-axis, the anti-phase I IgG antibody-titer (black triangle) is shown on the right y-axis. The course of antibiotic treatment is depicted above each graph.
Mentions: A 30-years-old man with a medical history of traumatic rupture of the thoracic aorta, for which he had undergone vascular surgery receiving an endoprosthesis, suffered from new symptoms of malaise, night sweats, weight loss, and chills. Because of the preceding Q fever epidemic, serology for C. burnetii was performed, revealing chronic infection with very high IgG titers against phase I and II (both 1:65536). PCR on serum for C. burnetii DNA was positive. He was not aware of a preceding acute Q fever episode. FDG-PET/CT showed no signs of infection at the thoracic aortic prosthesis, nor elsewhere. Transesophageal echocardiogram (TEE) showed mild aortic valve insufficiency without vegetations. Although infection of the vascular prosthesis could not be detected with FDG-PET/CT, it was considered the most likely focus of infection. The patient started antimicrobial therapy with doxycycline and hydroxychloroquine after which he made a quick clinical recovery. PCR in serum became permanently negative 5 months after start of therapy. Although anti-phase I IgG titers had decreased from 1:131072 to 1:8192 in 24 months, titers did not decrease further and moxifloxacin was added to the therapy. This regimen was continued for another 14 months, after which it was decided to stop treatment and continue follow-up 3-monthly. The follow-up –6 months so far– was uneventful. This patient, having a good response on the antimicrobial therapy, showed peaking of the IFN-γ/IL-2 ratio during the first 9 months. Thereafter, the ratio declined and was stable at lower values during the last phase of the treatment, analog to the anti-phase I antibody titers (Figure 1A).

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