Peripheral Helper T-cells in Common Variable ImmunoDeficiency (TAPDI)

Deciphering the Role of Peripheral Helper T-cells in Common Variable ImmunoDeficiency Pathophysiology in Patients With Non-infectious Complications

The aim is to determine whether whether Tph could support non-infectious complications through providing help to pathological B-cells.

Study Overview

• Status: Not yet recruiting
• Conditions: Common Variable Immunodeficiency
• Intervention / Treatment: Other: blood sample

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jean-François VIALLARD, Prof; Phone Number: +33 (0)5.57.65.64.83; Email: jean-françois.viallard@chu-bordeaux.fr
• Study Contact Backup: Name: Carine LOPEZ; Phone Number: +33 (0)5.24.54.91.32; Email: carine.lopez@chu-bordeaux.fr

Study Locations

• France
  • Pessac, France
    • CHU de Bordeaux - service de médecine interne
    • Sub-Investigator: Estibaliz LAZARO, Prof
    • Sub-Investigator: Camille PROT-LEURENT, MD
    • Sub-Investigator: Pierre DUFFAU, Prof
    • Principal Investigator: Jean-François VIALLARD, Prof
    • Sub-Investigator: Carine GREIB, MD
    • Contact: Jean-François VIALLARD, Prof; Phone Number: +33 (0)5.57.65.64.83; Email: jean-françois.viallard@chu-bordeaux.fr
    • Contact: Carine LOPEZ; Phone Number: +33 (0)5.24.54.91.32; Email: carine.lopez@chu-bordeaux.fr
    • Sub-Investigator: Emmanuel RIBEIRO, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Controls; Healthy controls	Other: blood sample; 48 ml whole blood for Peripheral blood mononuclear cell (PBMC) and serum isolation
Experimental: Common variable immunodeficiency	Other: blood sample; 48 ml whole blood for Peripheral blood mononuclear cell (PBMC) and serum isolation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ability of Tph to promote differentiation and antibody production by memory B cells (B-T co-culture)	At baseline (Day 0)

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Jean-François VIALLARD, Prof, University Hospital, Bordeaux; Study Director: Jonathan VISENTIN, Prof, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: November 19, 2025
• First Posted (Estimated): November 28, 2025

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: B cells; common variable immunodeficiency; peripheral helper T cells
• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes; Common Variable Immunodeficiency; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: CHUBX 2025/037

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No