To describe the prevalence of enteropathogenic viruses in children with primary (CVID and CVID-like disease) and secundary immunodeficiencies and a potential relation between this prevalence and the development of auto-/allo-immune enteropathy.
ID
Source
Brief title
Condition
- Gastrointestinal infections
- Immunodeficiency syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. The prevalence of enteropathogenic virus infections in children and
adolescents with CVID(-like disease) and SCT patients
2. An association between viral excretion and auto-/allo-immune enteropathy
Secondary outcome
1. The prevalence of symptomatic and asymptomatic enteropathogenic viral
infections in CVID(-like disease)
2. If any viruses are found: to assess
a. Duration of infection
b. Specification of the pathogen
c. Association between pathogen and clinical findings of the patient
3. To explore the potential differences in prevalence between the pediatric
CVID population, 'CVID-like disease' population and healthy
children/adolescents.
Background summary
Common Variable Immunodeficiency (CVID) is an immunodeficiency of unknown cause
that is characterised by an impaired B lymphocyte function, leading to e.g.
recurrent bacterial and viral gastrointestinal infections. It is known that
patients with such humoral immunodeficiencies can excrete viruses for several
years.
Additionally, a considerable subgroup of CVID and CVID-like patients suffers
from dysregulation of immune responses, causing chronic inflammation and/or
autoimmunity, such as auto-immune enteropathy. Recent clinical findings suggest
that chronic enteropathogenic viral infections can play a role in the
development of auto-immune enteropathy in CVID(-like disease).
These dysregulated immune responses are also recognized in children with
secondary immunodeficiency after stem cell transplantation. It is well-known
that these patients are at risk of developing an allo-immune enteropathy or
enteral Graft versus Host Disease. The recent finding of an association between
plasma human herpes virus 6 and the development of pulmonal GVHD, combined with
our own pilot findings of a substantial prevalence of gastrointestinal viruses
in the stools of SCT patients, led us to hypothesize that chronic carriership
of gastrointestinal viruses is associated with allo-immune enteropathy in SCT
patients.
Study objective
To describe the prevalence of enteropathogenic viruses in children with primary
(CVID and CVID-like disease) and secundary immunodeficiencies and a potential
relation between this prevalence and the development of auto-/allo-immune
enteropathy.
Study design
Follow up study in CVID and CVID-like disease patients aged 4-18 years, SCT
patients aged 0-17 years and a healthy control group, consisting of minimally
two and maximally 5 times an assessment of gastrointestinal complaints (not for
SCT patients and faecessampling (after 3-6-12 and 18/24 months, maximal
duration 2 years). De faeces samples will be screened by real time RT-PCR for
enteropathogenic viruses: adeno-, rota-, entero-, noro-, parecho-, astro- and
sapovirus. In addition, calprotectin will be tested, which is a parameter of
protein loss via the stool used regularly in patient care. PCR positivity will
lead to recurrent sampling to assess chronicity of the infection, and this will
be correlated to the gastrointestinal complaints. Data on the development of
auto-immune enteropathy will be extracted from the medical files and correlated
to the previously mentioned data.
The protocol for SCT patients is slightly different, as they do not have to
fill out questionnaires and faeces sampling will already be performed weekly
during their peri-SCT hospital admission. The only additional faecessampling
that will take place in the research setting is at 12 and 24 weeks post-SCT.
Study burden and risks
There are no risks associatied with the participation in this study.
Additionally, the burden of participation is very low: only 30 minutes or less
in two years, with no invasive procedures. On the other hand, there is no
direct benefit for the patients either.
Lundlaan 6 KC 03.063.0
Utrecht 3508 AB
NL
Lundlaan 6 KC 03.063.0
Utrecht 3508 AB
NL
Listed location countries
Age
Inclusion criteria
CVID: diagnosed according to the ESID criteria:
Normal to low numbers of B lymphocytes.
Impaired specific antibody production after immunisation (less than 4-fold titer increase after polysaccharide vaccination)
Low (<-2SD) serum immunoglobulin titers.
CVID-like disease: patients who do not fulfill the ESID criteria for CVID, but suffer from a similar clinical picture: at least one of the serum immunoglobulin(subclasses) is decreased (<-2SD), or there is insufficient antibody synthesis after immunisation less than 4-fold titer increase after polysaccharide vaccination). Secondly, patients suffer from recurrent infections, for which they are or have been treated with immunoglobulin substitution therapy for at least 6 months.
Healthy children: age 4-18 years
SCT patients: children aged 0-17 who will receive a stem cell transplantation (SCT) at the Wilhelmina Children's Hospital in order to treat their underlying disease, e.g. hematological malignancy, inborn metabolic disease such as Hurler's disease.
Exclusion criteria
For all patient groups: a proven primary immunodeficiency other than CVID, e.g. X-linked agammaglobulinemia (XLA) or hyper-IgM syndrome (HIGM), or a strong suspicion of one of these diseases.
For the healthy controls and SCT patients: immune disease, pre-existent gastrointestinal tract disease (e.g. Morbus Crohn, celiac disease, ulcerative colitis)
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 | NL25746.041.08 |