Association of TNFAIP3 With Immune-mediated TTP (A20iTTP)

Association of the TNFAIP3 Genomic Locus With Immune-mediated TTP

This study aims to investigate whether genetic variation in the TNFAIP3 locus is associated with immune-mediated thrombotic thrombocytopenic purpura (iTTP), and whether such association is mediated by decreased expression of A20 (TNFAIP3). The study includes a case-control design to assess genotype-expression association and a cohort study to evaluate clinical outcomes such as disease relapse.

Study Overview

• Status: Recruiting
• Conditions: Thrombotic Thrombocytopenic Purpura, Acquired
• Intervention / Treatment: Procedure: blood sampling

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ilaria Mancini, PhD; Phone Number: +390255035414; Email: ilaria.mancini@guest.unimi.it

Study Locations

• Italy
  • Milan, Italy, 20122
    • Recruiting
    • Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
    • Contact: Ilaria Mancini, PhD; Phone Number: +390255035414; Email: ilaria.mancini@guest.unimi.it
    • Principal Investigator: Ilaria Mancini, PhD
    • Sub-Investigator: Andrea Artoni, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Patients:

Inclusion Criteria:

• Diagnosis of iTTP
• Above 12 years of age
• Caucasian, Italian origin
• Written informed consent to participate in the study

Exclusion Criteria:

• Patients who do not meet the above-listed criteria will be excluded from participation in the study.

Controls will be healthy Italian volunteers of Caucasian ethnicity, with no history of thrombotic thrombocytopenic purpura, frequency-matched to cases by age and sex, and who have provided written informed consent to participate in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients with iTTP; Intervention: blood sampling during standard collection for routine testing, with additional sample for experimental analyses.	Procedure: blood sampling; Blood sampling for experimental analyses.
Other: Healthy donors; Intervention: blood sampling during standard donation, with an additional sample collected for experimental analyses.	Procedure: blood sampling; Blood sampling for experimental analyses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Allele frequency of TNFAIP3 variants in cases vs controls	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TNFAIP3 (A20) mRNA expression levels in peripheral blood	TNFAIP3 (A20) mRNA expression levels in peripheral blood of cases versus controls	Baseline
Association between TNFAIP3 genotype and gene expression		Baseline
Clinical relapse rate of iTTP during follow-up	Association between TNFAIP3/A20 variation and iTTP relapse in iTTP patients	Baseline
Severity of acute iTTP episodes	Association between TNFAIP3/A20 variation and the severity of acute iTTP (composite endpoint including death, treatment refractoriness, exacerbation, and prolonged disease course)	Baseline
Age at iTTP onset	Association between TNFAIP3/A20 variation and age at onset in iTTP patients	Baseline

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Investigators: Principal Investigator: Ilaria Mancini, PhD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2025
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: April 7, 2025
• First Submitted That Met QC Criteria: April 7, 2025
• First Posted (Actual): April 15, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: iTTP; A20; TNFAIP3
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Thrombocytopenia; Thrombophilia; Thrombotic thrombocytopenic purpura, acquired; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: A20iTTP; 2022-0469 (Other Grant/Funding Number: Fondazione Cariplo)

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
• product manufactured in and exported from the U.S.: No