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Antibody responses to borrelia IR6 peptide variants and the C6 peptide in Swedish patients with erythema migrans
Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
Haartman Institute, Helsinki.
Haartman Institute, Helsinki.
Lund University Hospital.
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2009 (English)In: International Journal of Medical Microbiology, ISSN 1438-4221, Vol. 299, no 6, 439-446 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to evaluate the antibody responses to different VlsE protein IR6 peptide variants and the synthetic C6 peptide in acute and convalescent (2-3 and 6 months) serum samples from Swedish patients with clinical erythema migrans (EM). Serum samples were prospectively collected from 148 patients with EM and compared to serum samples obtained from 200 healthy blood donors. The IgG responses to 3 IR6 peptide variants originating from Borrelia burgdorferi (B. burgdorferi) sensu stricto, B. garinii, and B. afzelii were measured by enzyme-linked immunosorbent assays (ELISAs) and compared to a commercial C6 peptide ELISA. Seropositivity rate in the IR6 or C6 peptide ELISAs ranged from 32% to 58% at presentation, 30-52% after 2-3 months, and 20-36% after 6 months. At presentation, positive antibodies in any of the 4 ELISAs were found in 66%. In 7/52 (13%), C6-negative EM cases, serological reaction was found to the B. burgdorferi sensu stricto-derived IR6 peptide. In patients reporting previous LB compared to those without previous LB, significantly higher seropositivity rates were noted for all IR6 peptides, but not for the C6 peptide. In the serology of EM in Europe, C6 ELISA does not seem to cover all cases. An ELISA using a mixture of B. burgdorferi sensu stricto IR6 peptide and the C6 peptide could be of value in the serodiagnosis of LB in Europe. Further studies on combinations of variant IR6 peptides and the C6 peptide in other manifestations of LB are needed to address this issue.

Place, publisher, year, edition, pages
2009. Vol. 299, no 6, 439-446 p.
Keyword [en]
C6; ELISA; Erythema migrans; IR6 peptide; Lyme borreliosis; Serology
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-21262DOI: 10.1016/j.ijmm.2008.10.006OAI: diva2:241040
Original Publication: Ivar Tjernberg, H. Sillanpaa, I. Seppala, I. Eliasson, Pia Forsberg and P. Lahdenne, Antibody responses to borrelia IR6 peptide variants and the C6 peptide in Swedish patients with erythema migrans, 2009, International Journal of Medical Microbiology, (299), 6, 439-446. Copyright: Elsevier Science B. V. Amsterdam Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2011-02-18
In thesis
1. Laboratory Diagnosis of Lyme Borreliosis: Anti-Borrelia Antibodies and the Chemokine CXCL13
Open this publication in new window or tab >>Laboratory Diagnosis of Lyme Borreliosis: Anti-Borrelia Antibodies and the Chemokine CXCL13
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lyme borreliosis (LB), the most common tick-borne disease in Europe and North America, is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. The spirochetes can invade several different organs, thereby causing many different symptoms and signs. Diagnosis of LB relies on patient history, physical examination, and detection of anti-Borrelia antibodies. However, anti-Borrelia antibodies are not always detectable, and they commonly persist even after LB is successfully treated or spontaneously healed.

The aim of my work was to study diagnostic aspects on clinical cases of LB and control subjects in an area endemic to LB, with a focus on newly developed anti-Borrelia antibody tests. A total of 617 patients with symptoms and/or signs consistent with LB, as well as 255 control subjects, were studied. The diagnostic panel included the following new LB tests: Immunetics Quick ELISA C6 Borrelia assay kit (C6), invariable region 6 peptide antibody assays (IR6), Liaison Borrelia CLIA (Li) and the chemokine CXCL13. Results were compared with the older Virotech Borrelia burgdorferi ELISA (VT) and with a Western blot method, the Virotech Borrelia Ecoline IgG/IgM Line Immunoblot (WB EL), when appropriate.

In general, no significant differences were noted between the C6, VT and Li tests regarding serosensitivity in various LB manifestations. However, the seropositivity rate was lower for the C6 test compared with the VT and Li tests 2–3 and 6 months after diagnosis of erythema migrans (EM), indicating normalization of antibody levels. In addition, EM patients reporting a previous LB episode had a C6 seropositivity rate similar to that of patients without a previous LB episode, and seroprevalence in healthy blood donors was lower in the C6 test than the VT and Li tests. Taken together, these results support the recommendation of the serum C6 test as a Borrelia serological test due to its ability to reflect ongoing or recent infection.

Although the majority of EM patients at presentation showed concordant serological responses to IR6 peptides representing the three main Borrelia species and the C6 peptide, there were also clinical EM cases that were C6-negative and could be detected mainly by a seroresponse to a B. burgdorferi sensu stricto-derived IR6 peptide. Thus, an antibody test combining antigens could be of value in the serodiagnosis of LB in Europe.

The serosensitivity of the C6 test in cases of Lyme neuroborreliosis (LNB) was shown to be associated with symptom duration. A serosensitivity rate of 93% was found in LNB patients ³ 12 years of age with a symptom duration of more than 30 days. Therefore, a negative C6 test in serum in such a patient argues against an LNB diagnosis.

The presence of chemokine CXCL13 in cerebrospinal fluid was confirmed to be a reliable marker of LNB. CXCL13 differentiated LNB from other conditions and also indicated a high probability of LNB in children with short symptom duration where anti-Borrelia antibodies were still lacking in the cerebrospinal fluid.

A two-tiered approach (C6 test in combination with WB EL) showed no significant improvement in specificity over the C6 test alone. However, WB EL may be useful in diagnosing suspected cases of acrodermatitis chronicum atrophicans and Lyme arthritis, usually displaying multiple IgG bands.

In conclusion, although the serodiagnosis of LB remains to be settled, this thesis provides some practical tools regarding the use and interpretation of Borrelia serology including proposed diagnostic routines.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 103 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1222
National Category
Infectious Medicine
urn:nbn:se:liu:diva-65728 (URN)978-91-7393-256-1 (ISBN)
Public defence
2011-03-18, Epidemin, Länssjukhuset i Kalmar, Kalmar, 13:00 (Swedish)
Available from: 2011-02-18 Created: 2011-02-18 Last updated: 2013-11-08Bibliographically approved

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