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

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.

Sex

All

Minimum age

18 Years

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