Improved laboratory diagnostics of Lyme neuroborreliosis in children by detection of antibodies to new antigens in cerebrospinal fluid.
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.
Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköoping University, Sweden. barbro.hedinskogman@ltdalarna.se
Barbro H
BH
Skogman
Stefan
S
Croner
Pia
P
Forsberg
Jan
J
Ernerudh
Pekka
P
Lahdenne
Heidi
H
Sillanpää
Ilkka
I
Seppälä
D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology; D000328:Adult; D000907:Antibodies, Bacterial / Q000134:cerebrospinal fluid*; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D025065:Borrelia burgdorferi / Q000235:genetics / Q000276:immunology; D015748:Borrelia burgdorferi Group / Q000235:genetics / Q000276:immunology; D002555:Cerebrospinal Fluid / Q000276:immunology*; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006801:Humans; D020852:Lyme Neuroborreliosis / Q000175:diagnosis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C112557:DdpB protein, Borrelia burgdorferi; C079616:OspC protein; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; C094442:cyclic peptide 24-41C; C106209:p35 antigen, Borrelia