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Improved Laboratory Diagnostics of Lyme Neuroborreliosis in Children by Detection of Antibodies to New Antigens in Cerebrospinal Fluid

Skogman, Barbro H. MD*†; Croner, Stefan MD, PhD*#; Forsberg, Pia MD, PhD*; Ernerudh, Jan MD, PhD*; Lahdenne, Pekka MD, PhD‡; Sillanpää, Heidi MSc§; Seppälä, Ilkka MD, PhD§¶

Pediatric Infectious Disease Journal: July 2008 - Volume 27 - Issue 7 - pp 605-612
doi: 10.1097/INF.0b013e31816a1e29
Original Studies

Background: Laboratory diagnostics in Lyme neuroborreliosis need improvement. We hereby investigate 4 new recombinant or peptide Borrelia antigens in cerebrospinal fluid in children with neuroborreliosis to evaluate their performance as diagnostic antigens.

Methods: An enzyme-linked immunosorbent assay was used to detect IgG antibodies to recombinant decorin binding protein A (DbpA), BBK32, outer surface protein C (OspC), and the invariable region 6 peptide (IR6). The recombinant antigens originated from 3 pathogenic subspecies; Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi sensu stricto. Cerebrospinal fluid and serum from children with clinical features indicative for neuroborreliosis (n = 57) were analyzed. Classification of patients was based on clinical symptoms and laboratory findings. Controls were children with other neurologic diseases (n = 20) and adult patients with no proven infection (n = 16).

Results: Sensitivity for DbpA was 82%, for BBK32 70%, for OspC 58% and for IR6 70%. Specificities were 94%, 100%, 97%, and 97%, respectively. No single antigen was superior. When new antigens were combined in a panel, sensitivity was 80% and specificity 100%. The reference flagella antigen showed a sensitivity of 60% and a specificity of 100%. Over all, the B. garinii related antigens dominated.

Conclusions: Recombinant DbpA and BBK32 as well as the peptide antigen IR6 perform well in laboratory diagnostics of neuroborreliosis in children. New antigens seem to improve diagnostic performance when compared with the routine flagella antigen. If different antigens are combined in a panel to cover the antigenic diversity, sensitivity improves further and a specificity of 100% can be achieve.

From the *Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköoping University; †Center for Clinical Research Dalarna, Falun, Sweden; ‡Hospital for Children and Adolescents, Helsinki University Central Hospital; §Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki; ¶HUSLAB Laboratory Services, University Central Hospital, Helsinki, Finland. #Dr. Croner died November 29, 2007.

Accepted for publication January 22, 2008.

The study is supported by grants from the County Council in ÖstergÖtland, the Center for Clinical Research in Dalarna (CKF), the Lions Foundation, the Samariten Foundation, the Health Research Council in the South East of Sweden (FORSS), the Finnish National Agency for Technology (Tekes), and Helsinki University Central Hospital Research Funds, Finland.

Address for correspondence: Barbro H. Skogman, MD, Center for Clinical Research Dalarna, Nissersv. 3, SE-791 82 Falun, Sweden. E-mail: barbro.hedinskogman@ltdalarna.se.

© 2008 Lippincott Williams & Wilkins, Inc.