Detection of IFN-γ Secretion by T Cells Collected Before and After Successful Treatment of Early Lyme Disease

Callister, Steven M.; Jobe, Dean A.; Stuparic-Stancic, Aleksandra; Miyamasu, Misato; Boyle, Jeff; Dattwyler, Raymond J.; Arnaboldi, Paul M.

doi:10.1093/cid/ciw112

Cited by 27 publications

(39 citation statements)

References 20 publications

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“…All but one of them [73] respected ESGBOR or IDSA clinical and microbiological definitions of LB. A QUADAS-2 quality assessment demonstrated low risk of bias and low applicability concerns for one study [67], low risk of bias and uncertainty regarding applicability for three studies [69,71,72], unclear risk of bias and unclear applicability concerns for one study [70], unclear risk of bias and high applicability concerns for two studies [66,68], and high risk of bias and high applicability concerns for one retrospective controlled study [73].…”

Section: Interferon-g Elispotmentioning

confidence: 99%

Unconventional diagnostic tests for Lyme borreliosis: a systematic review

Raffetin

Saunier²,

Bouiller

et al. 2020

Clinical Microbiology and Infection

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Background: Lyme borreliosis (LB) diagnosis currently relies mainly on serological tests and sometimes PCR or culture. However, other biological assays are being developed to try to improve Borrelia-infection diagnosis and/or monitoring. Objectives: To analyse available data on these unconventional LB diagnostic assays through a systematic literature review. Methods: We searched PubMed and Cochrane Library databases according to the PRISMA-DTA method and the Cochrane Handbook for Systematic Reviews of Interventions. We analysed controlled and uncontrolled studies (published 1983e2018) on biological tests for adults to diagnose LB according to the European Study Group for Lyme Borreliosis or the Infectious Diseases Society of America definitions, or identify strongly suspected LB. Two independent readers evaluated study eligibility and extracted data from relevant study reports; a third reader analysed full texts of papers to resolve disagreements. The quality of each included study was assessed with the QUADAS-2 evaluation scale. Results: Forty studies were included: two meta-analyses, 25 prospective controlled studies, five prospective uncontrolled studies, six retrospective controlled studies and two case reports. These biological tests assessed can be classified as: (i) proven to be effective at diagnosing LB and already in use (CXCL-13 for neuroborreliosis), but not enough to be standardized; (ii) not yet used routinely, requiring further clinical evaluation (CCL-19, OspA and interferon-a); (iii) uncertain LB diagnostic efficacy because of controversial results and/or poor methodological quality of studies evaluating them (lymphocyte transformation test, interferon-g, ELISPOT); (iv) unacceptably low sensitivity and/or specificity (CD57 þ natural killer cells and rapid diagnostic tests); and (v) possible only for research purposes (microscopy and xenodiagnoses). Discussion: QUADAS-2 quality assessment demonstrated high risk of bias in 25/40 studies and uncertainty regarding applicability for 32/40, showing that in addition to PCR and serology, several other LB diagnostic assays have been developed but their sensitivities and specificities are heterogeneous and/or under-evaluated or unassessed. More studies are warranted to evaluate their performance parameters.

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Section: Interferon-g Elispotmentioning

confidence: 99%

Unconventional diagnostic tests for Lyme borreliosis: a systematic review

Raffetin

Saunier²,

Bouiller

et al. 2020

Clinical Microbiology and Infection

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“…Other assays detect cytokines which are secreted by T cells upon stimulation with Borrelia antigens, such as the Quantiferon test described by Callister et al . or the enzym‐linked immunosorbent spot (ELISpot) assay (iSpot Lyme) described by Jin et al . .…”

Section: Introductionmentioning

confidence: 99%

“…Some of these assays are based on the proliferation of T cells, such as the lymphocyte transformation test (LTT) described by von Baehr et al [13] or the LTT-memory lymphocyte immunostimulation assay (MELISA) described by Valentine-Thon et al [14]. Other assays detect cytokines which are secreted by T cells upon stimulation with Borrelia antigens, such as the Quantiferon test described by Callister et al [15] or the enzym-linked immunosorbent spot (ELISpot) assay (iSpot Lyme) described by Jin et al [16]. Most studies on cellular assays have used poorly described study populations and lack clinical validations.…”

Section: Introductionmentioning

confidence: 99%

Prospective comparison of two enzyme-linked immunosorbent spot assays for the diagnosis of Lyme neuroborreliosis

Gorkom

Voet

Sankatsing

et al. 2020

Clinical and Experimental Immunology

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Summary Commercial cellular tests are used to diagnose Lyme borreliosis (LB), but studies on their clinical validation are lacking. This study evaluated the utility of an in‐house and a commercial enzyme‐linked immunosorbent spot (ELISpot) assay for the diagnosis of Lyme neuroborreliosis (LNB). Prospectively, peripheral blood mononuclear cells (PBMCs) were isolated from patients and controls and analysed using an in‐house Borrelia ELISpot assay and the commercial LymeSpot assay. B. burgdorferi B31 whole cell lysate and a mixture of outer surface proteins were used to stimulate the PBMCs and the numbers of interferon‐gamma‐secreting T cells were measured. Results were evaluated using receiver operating characteristic (ROC) curve analysis. Eighteen active and 12 treated LNB patients, 10 healthy individuals treated for an early (mostly cutaneous) manifestation of LB in the past and 47 untreated healthy individuals were included. Both assays showed a poor diagnostic performance with sensitivities, specificities, positive and negative predictive values ranging from 44.4–66.7%, 42.0–72.5%, 21.8–33.3% and 80.5–87.0%, respectively. The LymeSpot assay performed equally poorly when the calculation method of the manufacturer was used. Both the in‐house and the LymeSpot assay are unable to diagnose active LNB or to monitor antibiotic treatment success.

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“…In addition, IFN-γ and IFN-responsive genes are expressed in the joints of B. burgdorferi -infected mice [59, 60]. Surprisingly, the levels of IFN-γ did not correlate with the severity of other symptoms in a study performed by Callister et al [61]. …”

Section: Introductionmentioning

confidence: 99%

When a patient suspected with juvenile idiopathic arthritis turns out to be diagnosed with an infectious disease – a review of Lyme arthritis in children

2017

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The Lyme arthritis is a common manifestation of infection with Borrelia burgdorferi spirochete. Despite its infectious background, the inflammation clinically and histopatologically resembles juvenile idiopathic arthritis. As it affects a considerable number of Lyme disease patients, it should be routinely considered in differential diagnosis. Development of arthritis is partially dependent on spirochetal factors, including the ribosomal spacer type and the sequence of outer surface protein C. Immunological background involves Th1-related response, but IL-17 provides an additional route of developing arthritis. Autoimmune mechanisms may lead to antibiotic-refractory arthritis. The current diagnostic standard is based on a 2-step testing: ELISA screening and immunoblot confirmation. Other suggested methods contain modified two-tier test with C6 ELISA instead of immunoblot. An initial 28-day course of oral antibiotics (doxycycline, cefuroxime axetil or amoxicillin) is a recommended treatment. Severe cases require further anti-inflammatory management. Precise investigation of new diagnostic and therapeutic approaches is advisable.

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Detection of IFN-γ Secretion by T Cells Collected Before and After Successful Treatment of Early Lyme Disease

Abstract: Our findings suggest that measurement of IFN-γ after incubating blood with Borrelia antigens could be useful in the laboratory diagnosis of early Lyme disease. Also, after antibiotic treatment, this response appears to be short lived.

Cited by 27 publications

References 20 publications

Unconventional diagnostic tests for Lyme borreliosis: a systematic review

Unconventional diagnostic tests for Lyme borreliosis: a systematic review

Prospective comparison of two enzyme-linked immunosorbent spot assays for the diagnosis of Lyme neuroborreliosis

When a patient suspected with juvenile idiopathic arthritis turns out to be diagnosed with an infectious disease – a review of Lyme arthritis in children

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