To further study the mechanisms responsible for the Borrelia induced inhibition of antigen presentation and the impaired immuneresponse in Lyme disease pat¡ents, we would like to assess the immunological changes that occur in patients with a…
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Brief title
Condition
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess immunological changes in patients with acute, early Lyme borreliosis.
The main parameters and endpoints are immunological determinants such as the
expression of antigen presentation markers (e.g.
CD74, HLA-DR, HLA-DM) and the adaptive immune response by measuring cytokine
production.
Secondary outcome
1) To determine the role and mechanism of antigen presentation inhibition in
the development of acute, early Borrelia infection and
disseminated Lyme disease in patients.
2) To assess thê impact of immunological changes on acute, localized, early and
late disseminated Lyme borreliosis.
3) To study the effect of Borrelia-induced antigen presentation inhibition on
the adaptive immune response.
4) To evaluate which changes in confirmed patients are still existent several
months after diagnosis and/or treatment.
Background summary
One olthe major clinical needs for Lyme disease is a robust diagnostic assay to
identify Lyme disease in patients. Pathogenomic
signs such as the development of an erythema migrans (EM) are currently used to
diagnose patients with Lyme disease, however,
these signs don't develop in all patients. Standard serological tests (ELISA
and Western blot) for diagnosing Lyme disease have
limitations, such as a low sensitivity in acute, early infection, and lgG
positivity for years after infection. Current data suggest the
presence of an impaired or weak immune response toward B. burgdorferi sensu
lato. ln vitro and ex vivo data demonstrate that
Borrelia bacteria strongly downregulate genes and proteins involved in antigen
presentation. Antigen presentation by monocytes,
macrophages and DCs was inhibited, interfering with crucial steps for optimal
T-cell and B-cell response, towards Borrelia bacteria
and/or Borrelia antigens. Providing a possible explanation for why Lyme disease
patients do not develop an effective immune
response and thus leading to survival of the Borrelia spirochetes.
Study objective
To further study the mechanisms responsible for the Borrelia induced inhibition
of antigen presentation and the impaired immune
response in Lyme disease pat¡ents, we would like to assess the immunological
changes that occur in patients with a specifìc focus
on Borrelia-induced inhibition of antigen presentation innate immune cells,
their communication with and effects on the development
of an adaptive immune response.
Study design
This is a prospective cohort study with a three- till twelve month follow-up,
depending on the early findings, and a total duration of 1
year.
Study burden and risks
Minimal, there is a small chance of developing a hematoma or vasovagal reaction
at blood withdrawal. The participants will fill out
questionnaires at each measurement point. There is no direct benefit for
participating in the study.
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
Patients with acute localized infection:
- Patients must be 18 years or older;
- Must have a confirmed erythema migrans (EM) with a diameter of more than or 5
cm that has been present for
less than a week, the diagnosis being confirmed by the treating physician after
inclusion;
- Have not yet started treatment for the lyme borreliosis (LB) at the moment of
inclusion or at most one week prior
to the moment of inclusion;
- Do not have signs or symptoms at inclusion attributed to a previous episode
of Lyme borreliosis;
- If the patient has presented with EM's or Lyme borreliosis related symptoms
before inclusion, but no longer have,
this will be recorded in their patient file/through the questionnaire.
Patients with disseminated or post-treatment lyme borreliosis syndrome (PTLBS):
- Patients must be 18 years or older;
- Must have a conflrmed diagnosis of Lyme borreliosis, with clinical and
laboratory criteria largely based on the
case definitions of ESGBOR and published by Stanek et al.;
- Must have started treatment at most 1 week before inclusion.
Healthy controls:
- Patients must be 18 years or older;
- Patients must have bacterial skin/soft tissue infections (e.g. erysipelas,
cellulitis) and they must have a confirmed
diagnosis according to the leading guidelines.
Cross-reactive controls:
- Patients must be 18 years or older;
- Patients must be diagnosed with either erysipelas or cellulitis
Exclusion criteria
Patients with acute and localized LB or disseminated LB/PTLBS:
- Suffering from other tick-borne or infectious diseases;
- Suffering from severe immunological deficiencies that result in consistent
immunosuppression;
- The use of immunosuppressive medication before, during and/or after infection;
- The use of immunomodulating medication including > 7,5 mg prednisone daily,
methotrexate, biologicals;
- Unable to give informed consent or do not have a thorough command of the
Dutch language.
Healthy controls:
- Unable to give informed consent or do not have a thorough command of the
Dutch language;
- Suffering from other tick-borne or infectious diseases, HIV seropositivity if
known, active syphilis or leptospirosis,
an active infection with EBV/CMV;
- Suffering from auto-immune disease if known
- The use of immunosuppressive medication before, during and after Borrelia
infection occurred;
- The use of immunomodulating medication including > 7,5 mg prednisone daily,
methotrexate, biologicals;
- Severe immunological defìciencies that result in consistent immunosuppression.
- Known (severe) immunodeficiencies, hematologic malignancies in the medical
history or chemotherapy in the
last year;
- Current LB with typical symptoms;
- Other co-morbidities such as auto-immune diseases, severe acute and chronic
infections.
Cross-reactive controls:
- Unable to give informed consent or do not have a thorough command of the
Dutch language;
- Suffering from other tick-borne diseases;
- The use of immunomodulating medication including > 7,5 mg prednisone daily,
methotrexate, biologicals,
consistent immunosuppression;
- Other co-morbidities.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL69332.091.19 |