Background: Current laboratory markers do not readily detect acute Lyme disease. We assessed the utility of complement and its split products as markers of Lyme disease in patients shortly after a tick bite. Methods: Thirty-one consecutive acute Lyme disease patients, 14 with and 17 without erythema migrans (EM) skin rash, seen by a physician within 96 h of a tick bite were matched with 24 consecutive tick bite patients without Lyme disease symptoms and 46 healthy control subjects. Complement and split products measured included factor B, Bb, C4, C3c, C3ades Arg, C4ades Arg, C1q- and C3d-containing immune complexes, and C2. Results: C2, C4, C3 and factor B levels were within normal ranges in all groups. C3a and C4a levels were significantly higher in acute Lyme disease patients than in tick bite and healthy control groups (both p < 0.001). All acute Lyme disease patients, regardless of EM, had elevated levels of C3a or C4a. Few tick bite controls had elevated levels of C3a (2/20) or C4a (5/24) and only 1 of the healthy control subjects had elevated C3a (0/46) or C4a (1/32). Conclusions: These findings suggest that C3a and C4a may be useful markers of Lyme disease in patients seen shortly after tick bite, even in those without EM.

1.
Steere AC, Coburn J, Glickstein L: The emergence of Lyme disease. J Clin Invest 2004;113:1093–1109.
2.
Barbour AG, Hayes SF: Biology of Borrelia species. Microbiol Rev 1986;50:381–400.
3.
Centers for Disease Control and Prevention (CDC): Lyme disease – United States, 2001–2002. MMWR Morb Mortal Wkly Rep 2004;53:365–369.
4.
Steere AC: Lyme disease. N Engl J Med 2001;345:115–125.
5.
Tibbles CD, Edlow JA: Does this patient have erythema migrans? JAMA 2007;297:2617–2627.
6.
Engstrom SM, Shoop E, Johnson R: Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. J Clin Microbiol 1995;33:419–427.
7.
Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP: Diagnosis of lyme borreliosis. Clin Microbiol Rev 2005;18:484–509.
8.
Schutzer SE, Coyle PK, Belman AL, Golightly MG, Drulle J: Sequestration of antibody to Borrelia burgdorferi in immune complexes in seronegative Lyme disease. Lancet 1990;335:312–315.
9.
Artsob H, Huibner S: Complement fixation test for the diagnosis of Lyme disease. J Clin Microbiol 1990;28:637–638.
10.
Brunner M, Sigal LH: Use of serum immune complexes in a new test that accurately confirms early Lyme disease and active infection with Borrelia burgdorferi. J Clin Microbiol 2001;39:3213–3221.
11.
Schutzer SE, Coyle PK, Reid P, Holland B: Borrelia burgdorferi-specific immune complexes in acute Lyme disease. JAMA 1999;282:1942–1946.
12.
Zhong W, Oshmann P, Wellensiek HJ: Detection and preliminary characterization of circulating immunocomplexes in patients with Lyme disease. Med Microbiol Immunol 1997;186:153–158.
13.
Nadelman RB, Nowakowski J, Fish D, Nadelman RB, Nowakowski J, Fish D, Falco RC, Freeman K, McKenna D, Welch P, Marcus R, Aguero-Rosenfeld ME, Dennis DT, Wormser GP, Tick Bite Study Group: Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodesscapularis tick bite. N Engl J Med 2001;345:79–84.
14.
Aronowitz R: Prevention of Lyme disease after tick bites. N Engl J Med 1993;328:136–139.
15.
Salazar JC, Pope CD, Sellati TJ, Feder HM Jr, Kiely TG, Dardick KR, Buckman RL, Moore MW, Caimano MJ, Pope JG, Krause PJ, Radolf JD, Lyme Disease Network: Coevolution of markers of innate and adaptive immunity in skin and peripheral blood of patients with erythema migrans. J Immunol 2003;171:2660–2670.
16.
Kochi S, Johnson R, Dalmasso A: Complement-mediated killing of the Lyme disease spirochete Borrelia burgdorferi: role of antibody in formation of an effective membrane attack complex. J Immunol 1991;146:3964–3970.
17.
Wooten RM, Ma Y, Yoder RA, Brown JP, Weis JH, Zachary JF, Kirschning CJ, Weis JJ: Toll-like receptor 2 is required for innate, but not acquired, host defense to Borreliaburgdorferi. J Immunol 2002;168:99–107.
18.
Kuo M, Lane R, Giclas P: A comparative study of mammalian and reptilian alternative pathway of complement-mediated killing of the Lyme disease spirochete (Borrelia burgdorferi). J Parasitol 2000;86:1223–1228.
19.
Kraiczy P, Sherka C Kirschfink M, Zipfel P, Brade V: Immune evasion of Borrelia burgdorferi: insufficient killing of pathogens by complement and antibody. Int J Med Microbiol 2002;33:141–146.
20.
Kraiczy P, Skerka C, Kirschfink M, Zipfel P, Brade V: Mechanism of complement resistance of pathogenic Borrelia burgdorferi isolates. Int Immunopharmacol 2001;1:393–401.
21.
Kraiczy P, Hartmann K, Hellwage J, Skerka C, Kirschfink M, Brade V, Zipfel PF, Wallich R, Stevenson B: Immunological characterization of the complement regulator factor H-binding CRASP and ERP proteins of Borreliaburgdorferi. Int J Med Microbiol 2004;293:152–157.
22.
Liang FT, Yan J, Mbow ML, Sviat SL, Gilmore RD, Mamula M, Fikrig E: Borrelia burgdorferi changes its surface antigenic expression in response to host immune responses. Infect Immunol 2004;72:5759–5767.
23.
Crother TR, Champion CI, Whitelegge JP, Aguilera R, Wu XY, Blanco DR, Miller JN, Lovett MA: Temporal analysis of antigenic composition of Borrelia burgdorferi during infection in rabbit skin. Infect Immunol 2004;72:5063–5072.
24.
Barbour A: Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med 1984;57:521–525.
25.
Bunikis J, Barbour A: Laboratory testing for suspected Lyme disease. Med Clin North Am 2002;86:311–340.
26.
Glovsky M, Ward P, Johnson K: Complement determinations in human disease. Ann Allergy Asthma Immunol 2004;93:513–525, 605.
27.
Gloor B, Stahel P, Muller C, Schmidt O, Buchler M, Uhl W: Predictive value of complement activation fragments C3a and sC5b-9 for development of severe disease in patients with acute pancreatitis. Scand J Gastroenterol 2003;38:1078–1082.
28.
Fitzgerald T: Activation of the classical and alternative pathways of complement by Treponema pallidum and Treponema vincentii. Infect Immun 1987;55:2066–2073.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.