Ignite Creation Date:
2024-05-06 @ 2:37 PM
Last Modification Date:
2024-10-26 @ 1:34 PM
Study NCT ID:
NCT04377867
Status:
UNKNOWN
Last Update Posted:
2020-05-08
First Post:
2020-05-03
Brief Title:
New Biomarkers for Diagnosis and Follow-up of Patients With LRBA or CTLA4 Deficiencies
Sponsor:
Marmara University
Organization:
Marmara University
Study Overview
Official Title:
Identification of New Immunopathogenic Mechanisms Associated With LRBA or CTLA4 Deficiencies
Status:
UNKNOWN
Status Verified Date:
2020-05
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Primary immune deficiencies PID are a group of chronic diseases characterized by recurrent infections Apart from recurrent infections in some of PIDs autoimmunity allergy or malignancy could be accompanied to the diseases Recently the advanced sequencing technologies have led to the identification of a growing number of novel PIDs including the immune dysregulation syndromes caused by loss of function mutations in the LRBA encoding lipopolysaccharide-responsive beige like anchor protein and CTLA4 encoding cytotoxic T lymphocyte antigen 4 genes which are in common associated with autoimmunity in addition to a predisposition to recurrent infections PIDs with autoimmune components usually tend to have a more protracted clinical course and poorer prognosis rendering early diagnosis and treatment more crucial The accurate diagnosis largely relies on the molecular diagnosis due to the significant overlaps between the phenotypic expression of these various genetic defects The project aims to provide better and early diagnosis for LRBA CTLA4 deficiencies by using basic and advanced immunological genetic and molecular assays and rendering an early targeting therapy for patients discover disease related new pathways and biomarkers that can be helpful during diagnosis and monitoring abatacept targeted therapy responses
Detailed Description:
Lipopolysaccharide-responsive beige-like anchor LRBA and cytotoxic T lymphocyte protein-4 CTLA-4 deficiencies are primary immunodeficiency characterized by recurrent sinopulmonary infections with hypogammaglobulinemia lymphoproliferation and immunodysregulation which presents by enteropathy cytopenias and autoimmune endocrinopathy LRBA plays a pivotal role in the intracellular trafficking of by CTLA4 re-routing it away from lysosomal degradation and back to the cell surface CTLA-4 is an key immune checkpoint protein that is constitutively expressed on fork-head box P3 FOXP3 regulatory T Treg cells and is also induced upon activation of conventional T cells LRBA deficiency results in very low CTLA4 expression which explains the phenotypic overlap between LRBA and CTLA4 deficient subjects Furthermore reduced Treg cells number and function have been demonstrated in LRBA-deficient patients Consequent upon this LRBA deficiency may manifest as an IPEX like disease with early onset autoimmunity
LRBA was originally described as a common variable immune deficiency CVID-like disease with autoimmunity To date different agents have been applied in the treatment of LRBA and CTLA4 deficiencies including corticosteroids intravenous immunoglobulin therapy IVIG sirolimus infliximab rituximab and azathioprine Some patients also benefit from hematopoietic stem cell transplantation HSCT which can be curative More recently studies have suggested the effectiveness of abatacept a CTLA4-Ig fusion protein in controlling disease-related immune dysregulatory phenotypes In addition some biomarkers like soluble CD25 and circulating T Follicular helper cTFH cells were described as useful to monitor patients disease activity Nevertheless the long-term effectiveness of abatacept is not well documented Also there is no established consensus as to the dose and frequency of abatacept therapy for the treatment of those diseases and which biomarker is most reliable for follow up of patients
Aims of this current study include
1 Provide better and early diagnosis for LRBA CTLA4 deficiencies by using basic and advanced immunological genetic and molecular assays and rendering an early targeting therapy for patients
2 Discover disease related new pathways and biomarkers that can be helpful during diagnosis and monitoring abatacept targeted therapy responses
LRBA was originally described as a common variable immune deficiency CVID-like disease with autoimmunity To date different agents have been applied in the treatment of LRBA and CTLA4 deficiencies including corticosteroids intravenous immunoglobulin therapy IVIG sirolimus infliximab rituximab and azathioprine Some patients also benefit from hematopoietic stem cell transplantation HSCT which can be curative More recently studies have suggested the effectiveness of abatacept a CTLA4-Ig fusion protein in controlling disease-related immune dysregulatory phenotypes In addition some biomarkers like soluble CD25 and circulating T Follicular helper cTFH cells were described as useful to monitor patients disease activity Nevertheless the long-term effectiveness of abatacept is not well documented Also there is no established consensus as to the dose and frequency of abatacept therapy for the treatment of those diseases and which biomarker is most reliable for follow up of patients
Aims of this current study include
1 Provide better and early diagnosis for LRBA CTLA4 deficiencies by using basic and advanced immunological genetic and molecular assays and rendering an early targeting therapy for patients
2 Discover disease related new pathways and biomarkers that can be helpful during diagnosis and monitoring abatacept targeted therapy responses
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None