Common Variable Immunodeficiency
Conditions
Keywords
common variable immunodeficiency, peripheral helper T cells, B cells
Brief summary
The aim is to determine whether whether Tph could support non-infectious complications through providing help to pathological B-cells.
Detailed description
Common variable immunodeficiency (CVID), the most common symptomatic primary immunodeficiency in adults, can associate recurrent infections with severe non-infectious complications. Unfortunately, there is still no absolute biomarker predicting which CVID patient will develop non-infectious complications. Thus, novel biomarkers which could help refining CVID patient prognosis require further investigations. Moreover, the immune mechanisms driving non-infectious complications remain elusive. Therefore, further insight into CVID pathophysiology is needed to discover new treatments for CVID patients with non-infectious complications (CVIDc). The preliminary results show that CVIDc patients have an increase of circulating peripheral helper T-cells (Tph) , in comparison with patients with infectious manifestations only (CVIDi) and healthy individuals (HI). Recently described, Tph express CXCR3, help memory B-cells and are found in inflamed tissues in auto-immune diseases. They represent a major reservoir of auto-reactive T-cells, suggesting that Tph are key to drive auto-immune processes. Some authors hypothesized that Tph can help atypical memory B-cells (ABCs), a B-cell subset which is involved in auto-immune disease pathophysiology and which is also expanded in CVIDc patients. The investigators observed that CXCR3+ cells were increased in the spleen of CVIDc patients in comparison with non-CVID controls. These CXCR3+ cells could correspond to Tph supporting extra-follicular reaction and then B-cell tolerance loss. The hypothesis is that alterations in T-B cell collaboration leads to the amplification of Tph in CVID patients. Tph could support non-infectious complications in target tissues through providing help to pathological B-cells such as ABCs. Using peripheral blood from CVIDc/CVIDi patients and HI, the investigators will determine whether Tph support pathological B cell activation in CVIDc patients using T-B co-cultures. Patients will be included during their routine follow-up, for one day.
Interventions
OTHERblood sample
48 ml whole blood for Peripheral blood mononuclear cell (PBMC) and serum isolation
Sponsors
University Hospital, Bordeaux
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female; * Age ≥ 18 years; * Standard criteria will be applied to diagnose CVID, specifically requiring: 1) low serum IgG level \<5 g/L, combined with low IgM- and/or IgA-isotype concentrations \<0.4 g/L or \<0.7 g/L, respectively; 2) poor antibody responses to immunization or infection; and 3) exclusion of other defined forms of secondary hypogammaglobulinemias. Patients meeting the definitional criteria for CVID will be included, regardless of the duration of the disease or the treatment received (gammaglobulins substitution or not); * Being affiliated to health insurance; * Willing to participate and to sign informed consent.
Exclusion criteria
* Patients on corticosteroids and/or immunosuppressants; * Patients with a primary immunodeficiency genetically characterized, such as Bruton disease our HyperIgM syndrome; * Patients with an active chronic infection; * Pregnant or breastfeeding women; * Persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ability of Tph to promote differentiation and antibody production by memory B cells (B-T co-culture) | At baseline (Day 0) |
Countries
France
Contacts
CONTACTJean-François VIALLARD, Prof
CONTACTCarine LOPEZ
PRINCIPAL_INVESTIGATORJean-François VIALLARD, Prof
University Hospital, Bordeaux
STUDY_DIRECTORJonathan VISENTIN, Prof
University Hospital, Bordeaux
Outcome results
None listed