AUTHOR=Valencic Erica , Da Lozzo Prisca , Tornese Gianluca , Ghirigato Elena , Facca Francesco , Piscianz Elisa , Faletra Flavio , Taddio Andrea , Tommasini Alberto , Magnolato Andrea 

TITLE=Clinical and Cytometric Study of Immune Involvement in a Heterogeneous Cohort of Subjects With RASopathies and mTORopathies

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 9 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.703613

DOI=10.3389/fped.2021.703613

ISSN=2296-2360

ABSTRACT=RASopathies and mTORopathies are groups of genetic syndromes associated with increased activation of the RAS-MAPK or the PI3K-AKT-mTOR pathway, resulting in altered cell proliferation during embryonic and postnatal development.
The RAS-MAPK and the PI3K-AKT-mTOR pathways are connected to each other and play a crucial role in adaptive immunity. However, with the exception of APDS, immune function has not been deeply studied in these disorders. 
We collected clinical and immunophenotypic data of a cohort of patients with RASopathies and mTORopathies.
Overall, we enrolled 47 patients (22 females, 25 males, age 2-40 years): 33 with neurofibromatosis type 1, 11 Noonan syndrome and 3 Bannayan-Riley-Ruvalcaba syndrome.
8 patients reported a history of invasive infections requiring hospitalization and intravenous antibiotic therapy. Only 3 patients reported a history of unusual, difficult-to-treat or deep-seated infection. Adenotonsillectomy was performed in 11 patients (24%). However, in most cases (83%) patients’ parents did not perceive their child as more prone to infections than their peers.
Lymphocyte subpopulations were analyzed in 37 of the 47 patients (16 female, 21 males, age 1-40 years). Among the studied lymphocyte subsets, the only consistent alteration regarded an increased percentage of immature B cells (recent bone marrow emigrants) in 34 out of 37 (91,9%) patients, and an increased percentage of double negative T cells in 9 patients.
In conclusion, although borderline immune abnormalities were present in a significant proportion of subjects and adenotonsillectomy was performed more frequently than expected for the general population, no major immune disturbance was found in this cohort of patients.