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M T Philipp

Publications and source records attributed to M T Philipp.

40 records · Page 3Linked to original sources

Borrelia burgdorferi antigens that are targeted by antibody-dependent, complement-mediated killing in the rhesus monkey.

We identified surface antigens of Borrelia burgdorferi that are targeted by antibody-dependent, complement-mediated killing (ADCK) in the rhesus monkey. For this purpose, we had available serum samples from three animals infected with B. burgdorferi JD1 by needle inoculation and from two monkeys that were infected with the same B. burgdorferi strain by Ixodes scapularis tick bite. Sera from monkeys from the first group contained antibodies to OspA and OspB detectable by Western blot (immunoblot) using whole B. burgdorferi antigens, whereas serum samples from animals in the second group did not. The targeting of OspA and OspB by functional antibodies was demonstrated directly by showing that ADCK was partially inhibited when antibodies were preincubated with an excess of soluble recombinant OspA or OspB. Simultaneous addition of OspA and OspB did not result in an additive inhibitory effect on ADCK, a result that suggests that the epitopes on OspA and that on OspB targeted by antibody in this mechanism are the same, or at least cross-reacting. The targeting of non-OspA, non-OspB surface antigens was inferred from the fact that sera from tick-inoculated animals, which did not contain detectable anti-OspA or anti-OspB antibodies, were able to effect ADCK. This killing effect was not inhibitable by the addition of recombinant OspA or OspB or both proteins together. We also showed that both immunoglobulin G and M antibodies participate in the ADCK mechanism in the rhesus monkey. Rhesus complement does not kill B. burgdorferi in vitro in the absence of antibody, and antibody alone is effective in killing only at serum dilutions lower than 1:15. However, such "complement-independent" antibodies were not present in all bleeds. Two main conclusions may be drawn from the analysis of our results. First, both OspA and OspB are targeted by the ADCK mechanism in the rhesus monkey. Second, one or more B. burgdorferi surface antigens that are neither OspA nor OspB also participate in ADCK.

Animals↗

Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans.

We demonstrate that Borrelia burgdorferi infection in the rhesus monkey mimics the early and early disseminated phases of human Lyme disease. Clinical, bacteriological, immunological, and pathological signs of infection were investigated during 13 weeks after inoculation of the spirochete. Three animals were given B. burgdorferi (strain JD1) by needle inoculations, six animals were exposed to the bite of B. burgdorferi-infected Ixodes dammini ticks, and three animals were uninfected controls. B. burgdorferi could be recovered from all animals that were given the spirochete. Bacteria were detectable until week 6 postinoculation (p.i.) in blood, until week 8 p.i. in skin biopsies, and at 10 weeks p.i. in the conjunctiva of one of two animals which developed conjunctivitis. Erythema migrans (EM) appeared in one of the three animals infected by needle inoculation and in five of the six animals infected by ticks. Deep dermal perivascular lymphocytic infiltrations (characteristic of human EM) were observed in all animals showing EM clinically. Both EM and conjunctivitis were documented concomitantly with the presence of the spirochete. Lethargy, splenomegaly, and cerebrospinal fluid pleocytosis were also noted in some animals, but the direct connection of these signs with the infection was not shown. The appearance rate of immunoglobulin M and immunoglobulin G antibodies to B. burgdorferi, as well as the antigen spectra recognized, were remarkably similar to those seen in humans. Serum antibodies from infected animals were able to kill B. burgdorferi in vitro in the presence of rhesus complement. The rhesus monkey model appears to be useful for the investigation of the immunology and pathogenesis of Lyme disease and for the development of immunoprophylactic, diagnostic, and chemotherapeutic protocols.

Animals↗

Positive IgG Western blot for Borrelia burgdorferi in Colombia.

In order to evaluate the presence of specific IgG antibodies to Borrelia burgdorferi in patients with clinical manifestations associated with Lyme borreliosis in Cali, Colombia, 20 serum samples from patients with dermatologic signs, one cerebrospinal fluid (CSF) sample from a patient with chronic neurologic and arthritic manifestations, and twelve serum samples from individuals without clinical signs associated with Lyme borreliosis were analyzed by IgG Western blot. The results were interpreted following the recommendations of the Centers for Diseases Control and Prevention (CDC) for IgG Western blots. Four samples fulfilled the CDC criteria: two serum specimens from patients with morphea (localized scleroderma), the CSF from the patient with neurologic and arthritic manifestations, and one of the controls. Interpretation of positive serology for Lyme disease in non-endemic countries must be cautious. However these results suggest that the putative "Lyme-like" disease may correlate with positivity on Western blots, thus raising the possibility that a spirochete genospecies distinct from B. burgdorferi sensu stricto, or a Borrelia species other than B. burgdorferi sensu lato is the causative agent. Future work will focus on a survey of the local tick and rodent population for evidence of spirochete species that could be incriminated as the etiologic agent.

Antibodies, Bacterial↗