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Can ELISPOT Be Applied to A Clinical Setting as A Diagnostic Utility for Neuroborreliosis?
Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
The Åland Borrelia Group, Åland, 22100 Mariehamn, Åland, Finland.
Center for Clinical Research (CKF) Dalarna, 791 36 Falun, Sweden.
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2012 (English)In: Cells, ISSN 2073-4409, Vol. 13, no 48, 153-167 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this prospective study was to investigate the diagnostic performance of Borrelia (Bb)-induced interferon (IFN)-γ secretion detected by ELISPOT modified to be feasible for clinical laboratories as a supplementary test to the laboratory diagnosis of Lyme neuroborreliosis (LNB) in an endemic setting. Between 2002 and 2004, patients with symptoms of suspected clinical LNB were included in a study conducted on the Åland islands in the Finnish archipelago, which is a hyper-endemic area for Lyme borreliosis (LB). Fourteen patients with confirmed LNB and 103 patients with non-LNB were included, and the numbers of spontaneous and Bb-induced IFN-γ-secreting cells were assayed by the ELISPOT test. The ELISPOT assay showed a weak diagnostic performance with a sensitivity of 36% and a specificity of 82%. The findings in this study show that this ELISPOT-assay modified to be feasible in clinical routine laboratories is not useful as a supplementary diagnostic tool in the laboratory diagnosis of patients with clinically suspected LNB.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI AG , 2012. Vol. 13, no 48, 153-167 p.
Keyword [en]
Borrelia burgdorferi; neuroborreliosis; ELISPOT; cerebrospinal fluid; diagnostic test; sensitivity; specificity
National Category
Other Clinical Medicine
URN: urn:nbn:se:liu:diva-80259DOI: 10.3390/cells1020153PubMedID: 24710421OAI: diva2:546329
Available from: 2012-08-23 Created: 2012-08-23 Last updated: 2015-10-23Bibliographically approved
In thesis
1. Tick-Borne Infections in Humans: Aspects of immunopathogenesis, diagnosis and co-infections with Borrelia burgdorferi and Anaplasma phagocytophilum
Open this publication in new window or tab >>Tick-Borne Infections in Humans: Aspects of immunopathogenesis, diagnosis and co-infections with Borrelia burgdorferi and Anaplasma phagocytophilum
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The tick-borne infectious agents, B. burgdorferi, A. phagocytophilum and the TBE-virus, can all cause clinical disease in humans and may all initially give rise to myalgia, arthralgia, headache and fever. The clinical manifestations of the infections range from subclinical or mild to severe, in some cases with a postinfectious sequel, and mixed infections may occur, confusing the clinical picture.

The aim of this thesis was to investigate the occurrence and co-existence of these infections in a Scandinavian context. A further aim was to study aspects of the immunopathogenesis of B. burgdorferi infection and possible effects on the immune response when previously exposed to A. phagocytophilum. Finally, an attempt was made to improve the laboratory diagnosis of Lyme neuroborreliosis (LNB).

In a prospective clinical study, patients were recruited based on two independent inclusion criteria; 1) patients with unspecific symptoms or fever, and 2) patients with erythema migrans (EM). Among 206 patients, we found 186 cases of Lyme borreliosis (LB) (174 with EM), 18 confirmed and two probable cases of human granulocytic anaplasmosis (HGA), and two cases of Tick-borne encephalitis (TBE). Thirteen of the HGA cases presented without fever. Furthermore, 22 of the EM patients had a subclinical co-infection with A. phagocytophilum, based on serology. Both TBE cases had co-infections, one with B. burgdorferi and one with A. phagocytophilum.

In another investigation, IL-12p70 secretion in patients with current LB was compared in patients with or without previous A. phagocytophilum infection. Patients with serological evidence of previous exposure to A. phagocytophilum had a lower B. burgdorferi-induced IL-12p70 secretion. Since IL-12p70 induces the Th1 response, this finding indicates a reduced Th1 response, possibly caused by A. phagocytophilum. In a separate study, we showed that patients with LNB had increased levels of cytokines associated with cytotoxicity in cerebrospinal fluid (CSF), including the recently described cytokine IL-17.

Since it is known that the adaptive immune system, especially the T cells, is activated during an infection with B. burgdorferi, a modified ELISPOT assay using cells from CSF was evaluated to be a useful complementary test in diagnosing LNB. However, we found that the diagnostic performance was too weak in our setting, and we could not recommend it for use in clinical laboratories at this stage.

In conclusion, tick-borne co-infections are probably quite common in Sweden. Our HGA cases were most often discovered as co-infections with LB and would probably have been missed during a routine consultation. They presented with mild symptoms and often without fever, which in previous reports has been part of the disease definition.

The immune response in LNB was shown to be compartmentalized to the target organ, also in terms of cytokine response. Furthermore, we found indications of possible long-term effects of A. phagocytophilum infection, demonstrated as a reduced IL-12p70 secretion in patients with ongoing LB. This could be a disadvantage when mounting a Th1 response to infection with B. burgdorferi. If this is so, the inter-play of these infectious agents in co-infections or consecutive infections may be of importance to clinical outcome.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 131 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1315
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-80260 (URN)978-91-7519-852-1 (ISBN)
Public defence
2012-09-07, Berzeliussalen, ingång 65, Campus US, Linköpings universitet, Linköping, 13:15 (Swedish)
Available from: 2012-08-23 Created: 2012-08-23 Last updated: 2013-08-29Bibliographically approved

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Nordberg, MarikaForsberg, PiaErnerudh, JanEkerfelt, Christina
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Infectious DiseasesFaculty of Health SciencesDepartment of Infectious DiseasesClinical ImmunologyDepartment of Clinical Immunology and Transfusion Medicine
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