Autoantibodies Against Type I Interferon in Patients Affected With Ph-negative Myeloproliferative Neoplasms (MPN-IFN Study)

Active, not recruiting

• Conditions: Myeloproliferative Disease; COVID - 19

• Registration Number: NCT07204366
• Lead Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Brief Summary

The classic Ph-negative myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic disorders caused by a dysregulated JAK/STAT signal transduction because of acquired somatic mutations of JAK2, CALR or MPL genes. Chronic inflammation may predispose to MPN development.

SARS-CoV-2 infection displays extreme interindividual clinical variability, ranging from asymptomatic infection to life-threatening coronavirus disease (COVID-19). Age is a major risk factor for severe disease. Male sex and medical comorbidities have minor impact. It was demonstrated that at least 3.5% of patients with life-threatening COVID-19 have monogenic inborn errors of TLR3- or TLR7-dependent type I interferons (IFN-I) immunity. It has also been described that at least 15% of patients with life-threatening COVID-19 have neutralizing autoantibodies (AAbs) against IFN-I, that precede SARS-CoV-2 infection.

As regard MPN, COVID-19 is associated with a mortality as high as 33%. Patients with MF had the highest mortality (48%), while patients with ET had the greatest risk of venous thromboembolism (16.7%).

In this prospective study, we want to search for AAbs against IFN-I in a cohort of MPN patients to evaluate their prevalence in the MPN population and to look for clinical correlations, including COVID-19 severity.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-05-06
• Status Verified: 2025-09
• Study First Submitted: 2025-09-24
• Study First Submitted QC: 2025-09-24
• Last Update Submitted: 2025-09-24
• Study First Posted: 2025-10-02
• Last Update Posted: 2025-10-02
• Primary Completion: 2030-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 219

Inclusion Criteria

• A diagnosis of PV, ET, prePMF, overt PMF or MPN-U according to 2016 WHO criteria
• Characterization of the MPN driver mutation performed at any moment before enrolment
• A peripheral blood (PB) sample collected at the enrolment visit suitable for plasma extraction and functional evaluation of anti-cytokine auto-Abs

Exclusion Criteria

• None

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate for the prevalence of AAbs neutralizing IFN-I in a cohort of Ph-neg MPN patients.	2 years

Secondary Outcome Measures

Name	Time	Method
To compare the prevalence of AAbs neutralizing IFN-I in a cohort of Ph-neg MPN patients to that estimated in the general population.	2 years
To check for association between the presence/subtype/title of AAbs to IFN-I and both clinical and molecular features of MPN patients	2 years
To check for association between use of specific cytoreductive therapy and the presence of AAbs to IFN-I in MPN patients	2 years
To check for association between presence/subtype/title of AAbs to IFN-I and COVID-19 severity among MPN patients who get SARS-CoV-2 infection	2 years

Trial Locations

Locations (1)

Fondazione IRCCS Policlinico San Matteo; 🇮🇹 Pavia, Lombardy, Italy