C3- JA C4-TASOJEN NOUSU BORRELIOOSISSA

[Bb]

Lähettäjä: Soijuv Lähetetty: 18.7.2005 11:08


C3a and C4a: Complement Split Products Identify Patients with Acute Lyme disease


R. Shoemaker¹, P. Giclas², D. House¹ and M.M. Glovsky³

¹Center for Research on Biotoxin Associated Illnesses, Pocomoke, Md

²National Jewish Research and Medical Center, Denver, Colorado

³Quest Nichols Diagnostics, Inc, San Juan Capistrano California


Abstract:

Background: Lyme disease, caused in the USA by infection with the tick-borne spirochete Borrelia burgdorferi, is an increasingly prevalent infectious disease.

Immune mediated inflammatory responses, both innate and acquired, are important in the eradication of the spirochete. Measurements of innate immune responses, especially complement, could serve as a marker for illness in patients seen shortly after a tick bite. To understand innate immune responses to early infection in Lyme disease, we explored the complement system in patients with a tick bite.

Methods: Complement tests were determined by nephelometry: C3, C4, C1q-IC, C3q-IC and Factor B; and by double diffusion with specific antibodies to C2. C3a and C4a were determined using kits provided by Quidel Labs, San Diego, CA. 18 consecutive patients with an erythema chronicum migrans (ECM) skin rash seen by a physician within 48 hours of a tick bite, were matched with 18 consecutive tick bite patients without ECM and without symptoms > 3 and 85 normal patients evaluated for routine physical exams.

Results: Complement determinations C2, C4, C3, C1q-IC, C3q-IC and Factor B were similar in all 3 groups. C3a and C4a anaphylatoxins were significantly higher (p<.001) in the acute Lyme patients compared with the tick bite controls and normal patients.

Conclusions: In acute Lyme disease, highly elevated levels of C3a and C4a are found in all patients but in none of tick bite controls and normals. We conclude that elevated C3a and C4a levels measured within 48 hours of a tick bite can separate acute Lyme disease patients needing therapy from patients with tick bites but no illness.

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MMP9, visual contrast sensitivity, C3a and C4a: New diagnostic aids in acute and chronic Lyme disease

Ritchie C Shoemaker¹, Dennis House¹

Center for Research on Biotoxin Associated Illnesses, Pocomoke, Md

Abstract:

Background: Lyme disease, caused in the USA by infection with the tick-borne spirochete Borrelia burgdorferi, is an increasingly prevalent infectious disease.

Prompt diagnosis can lead to early intervention, reducing morbidity from the illness. We have previously shown that levels of C3a and C4a, rising within 48 hours after a tick bite, are markers for Lyme disease when an ECM rash is present. Here we report C3a, C4a, matrix metalloproteinase-9 (MMP9) and visual contrast sensitivity (VCS) in patients with tick bite 3-14 days of presentation but without ECM as markers for acute Lyme disease. Following antibiotic treatment of cases identified by C3a, C4a, MMP9 and VCS, symptoms resolved in all non-ECM patients except for those patients with HLA DRB1-15, DQ-6-DRB5-51.

Methods: Baseline symptoms, VCS and labs were obtained in 20 consecutive patients with no history of Lyme disease presenting for evaluation of tick bite without ECM. Following informed consent, patients were treated with 21 days of antibiotics. Follow-up data were compared to baseline and to 85 matched non-bite patients.

Results: Symptoms, VCS deficits, elevation of C3a, C4a and MMP-9 were normal in non-bite controls and those with tick bite but less than 4 symptoms (n=9). In patients with symptoms > 4 after a tick bite (n=11), 9 had elevation of C3a, C4, MMP9 and a VCS deficit; two had C4a and VCS only. Eight patients in this group improved after antibiotics. The 3 non-responders each had HLA DR by PCR DRB1-15, DQ-6, DRB5-51. Subsequent treatment with cholestyramine (CSM) eliminated symptoms and returned lab values to equal controls.

Conclusions: In tick bite patients without ECM rash, a diagnosis of acute Lyme disease can be made before antibody testing would be of benefit by finding symptoms > 4 together with elevated levels of MMP-9, C3a and C4a and deficits in VCS. MMP9 and VCS were previously shown to be of little diagnostic benefit in case of tick bite less than 72 hours duration. Antibiotic therapy should be instituted in patients with multiple symptoms, awaiting lab results. For those patients with elevated markers but no response to therapy, HLA DR by PCR is indicated.