Conditions that promote IL-10 producing B cells in humans are still ill defined. In this project our aim is to investigate the frequnecy of IL-10 producing B cells in healthy volunteers. Next, we aim to compare this to the frequency of IL-10…
ID
Source
Brief title
Condition
- Allergic conditions
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
IL-10 producing B cells in PBMC
IL-4 producing T cells (Th2 cells) in reaction to relevant allergens
Secondary outcome
Total IgE and allergen-specific IgE, IgG1, IgG2a, IgG4, IgA in plasma and nose
washings.
Affinity of allergen-specific IgE molecules
TNFalpha and IL-10 in plasma and nose washings.
Molecular profiling of B cell populations with ATACseq
Background summary
In the last few decades, the incidence of childhood allergic asthma and
rhinitis has strongly increased. A possible explanation is the decreased
exposure to microbial molecules due to a decreased frequencies of childhood
infections. The hypothesis is that some of these microbial substances are able
to avoid immunity by active induction of tolerance. Simultaneously also
tolerance is raised against bystanders antigens, such as allergens. New
therapies could benefit from the use of microbial molecules to induce tolerance.
One example of a protective pathogen is the infection by parasitc worm
infections, associated with reduced frequencies in allergy and asthma.
Parasitic worms can suppress the immune system of the host for their own
survival. The hypothesis is that they not onlysuppress immune responses to
their own antigens, but also to bystander antigens such as allergens. Knowlegde
on how parasitic worm infections suppress the immune system can help to desing
new therapies and drugs to prevent or suppress allergic asthma or rhinitis.
Recently, our laboratory has found evidence for a new regulatory cell for
suppression of experimental allergic airway inflammation. These new findings
point towards an emerging role for IL-10 producing B cells in protection
against allergic asthma and rhinitis.
Study objective
Conditions that promote IL-10 producing B cells in humans are still ill
defined. In this project our aim is to investigate the frequnecy of IL-10
producing B cells in healthy volunteers. Next, we aim to compare this to the
frequency of IL-10 producing B cells in peripheral blood of allergic asthma or
rhinitis patients before and at different time points after the start of
immunotherapy, and at the same time investigate their inhibitory potential of
allergen-specific immune responses. Finally, we aim to investigate whether
worm-derived molecules are able to increase the frequency and activity of IL-10
producing B cells in peripheral blood cells from allergic asthma or rhinitis
patients in vitro, with the ultimate goal to suppress asthmatic and/or allergic
symptoms in vivo.
Study design
Healthy controls, allergic rhinitis and allergic asthma patients are
cross-sectional compared. Subsequently, allergic asthma and rhinitis patients
will be studied during a longitudinal follow-up at several time points after
the start of immunotherapy.
Study burden and risks
Standardized lung function tests are applied worldwide for the examination of
patients with asthma and are proven to be save. Nose washings are routinely
taken, are save and non-invasive. Venous blood for the laboratory assessment
will be collected by professionals.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
General inclusion criteria:
- Written informed consent
- Male and female persons, aged >= 18 years and <= 55 years;Specific inclusion criteria:
Group 1 (allergic rhinitis):
- moderate/severe allergic rhinitis (ARIA guidelines)
- PC20 of histamine > 16 mg/ml
- specific IgE >= 0.7 kU/l for tree or grass pollen and/or house dust mite (HDM)
- positive skin prick test response ( wheal > 5 mm) for tree or grass pollen and/or HDM
- total IgE >30 < 700 Iu/ml;Group 2 (allergic asthma):
- Clinical controlled asthma for at least 6 months according GINA guidelines, without severe exacerbations in the previous 6 months
- FEV1> 70% (short-acting β2-agonists if needed)
- History of episodic symptoms of wheezing, breathlessness, cough or chest tightness (>12 months)
- PC20 of histamine < 8 mg/ml
- a positive skin prick test response ( wheal > 5 mm) for tree or grass pollen and/or HDM
- specific IgE >= 0.7 kU/l for tree or grass pollen and/or house dust mite (HDM)
- total IgE >30 < 700 IU/ml;Group 3(healthy control group):
- negative SPT
- PC20 of histamine > 16 mg/ml
- Specific IgE < 0.7 kU/l for tree or grass pollen and/or house dust mite (HDM)
- Total IgE <100 IU/ml
Exclusion criteria
age < 18 yrs
smoking
pregnancy
airway infection
Severe/ instable chronic asthma
Specific IgE >= 0.7 kU/l for animals to which the patients has daily contact with
Immunotherapy for the last 5 years
Anatomical abnormalities of the nose
Contraindications for immunotherapy according to international guidelines
anti-IgE treatment previously
systemic steroids or suffered exacerbations in the last year
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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In other registers
| Register | ID |
|---|---|
| CCMO | NL28786.058.09 |