Neurologic and Immunologic Characteristics of CTLA-4 and LRBA Hereditary Deficiency

NCT05040256 | Completed

• 1 other identifier: RECHMPL21_0290
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

CTLA4 and LRBA deficiencies are rare genetic disorders, recently described, and associated with multiple clinical features. It ranges from recurrent infections, auto-immunity, and organ infiltration with lymphocytes. Neurologic syndroms are described in up to 30% of patients, yet they are poorly defined to date. Early recognition of a specific pattern can be important, given that there is a targeted therapy in this situation.

Conditions

CTLA4 Haploinsufficiency

Keywords

LRBA deficiency; Primary immunodeficiency; Neuroinflammation; Genetic diseases; Autoimmune diseases

Outcome Measures

Primary Outcomes (1)

• Number of Neurologic impairment

  Neurologic signs and symptoms (headaches, seizures…), cerebral MRI features, lumbar puncture, histopathology

  1 day

Secondary Outcomes (1)

• Presence of reccurent infections

  1 day

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients listed with CTLA4 or LRBA deficiency in the register of the national reference center for primary immunodeficiencies.

You may qualify if:

• \- Patients diagnosed with CTLA4 or LRBA mutation

You may not qualify if:

• \- Age \< 12 years

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

Uhmontpellier

Montpellier, 34295, France

Location

Related Publications (3)

• Schindler MK, Pittaluga S, Enose-Akahata Y, Su HC, Rao VK, Rump A, Jacobson S, Cortese I, Reich DS, Uzel G. Haploinsufficiency of immune checkpoint receptor CTLA4 induces a distinct neuroinflammatory disorder. J Clin Invest. 2020 Oct 1;130(10):5551-5561. doi: 10.1172/JCI135947.

  PMID: 32955488 RESULT

• Ayrignac X, Goulabchand R, Jeziorski E, Rullier P, Carra-Dalliere C, Lozano C, Portales P, Vincent T, Viallard JF, Menjot de Champfleur N, Rieux-Laucat F, Besnard C, Koenig M, Guissart C, Labauge P, Guilpain P. Two neurologic facets of CTLA4-related haploinsufficiency. Neurol Neuroimmunol Neuroinflamm. 2020 Jun 4;7(4):e751. doi: 10.1212/NXI.0000000000000751. Print 2020 Jul.

  PMID: 32499327 RESULT

• Schubert D, Bode C, Kenefeck R, Hou TZ, Wing JB, Kennedy A, Bulashevska A, Petersen BS, Schaffer AA, Gruning BA, Unger S, Frede N, Baumann U, Witte T, Schmidt RE, Dueckers G, Niehues T, Seneviratne S, Kanariou M, Speckmann C, Ehl S, Rensing-Ehl A, Warnatz K, Rakhmanov M, Thimme R, Hasselblatt P, Emmerich F, Cathomen T, Backofen R, Fisch P, Seidl M, May A, Schmitt-Graeff A, Ikemizu S, Salzer U, Franke A, Sakaguchi S, Walker LSK, Sansom DM, Grimbacher B. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med. 2014 Dec;20(12):1410-1416. doi: 10.1038/nm.3746. Epub 2014 Oct 20.

  PMID: 25329329 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Insulin-Dependent, 12; Primary Immunodeficiency Diseases; Neuroinflammatory Diseases; Genetic Diseases, Inborn; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Xavier Ayrignac, MD

  University Hospital, Montpellier

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: September 10, 2021
• Study Start: February 1, 2021
• Primary Completion: August 1, 2021
• Study Completion: September 30, 2021
• Last Updated: November 15, 2021

Record last verified: 2021-11

Locations

FR (1)