ESPE Abstracts

Background: ROHHAD(NET) syndrome has been proposed as an acquired neuroimmunological dysfunction. Aim of the study is to compare the phenotype of lymphocyte subpopulations in patients vs controls and to evaluate the plasma levels of pro-inflammatory cytokines/chemokines in ROHHADNET syndrome.

Patients and Methods: We included 14 patients (9F;5M), selected by clinical criteria, matched with 11 controls with simple obesity (7F;4M). Median BMI at sample day was respectively +3.8 SDS and +3.1 SDS. Lymphocyte subpopulations and pro-inflammatory cytokines/chemo kines were analyzed by Flow Cytometry performed on peripheral blood (PB) in the two groups. Furthermore, soluble HLA-G (sHLA-G) and soluble HLA-E (sHLA-E) were assessed through Enzyme-Linked Immunosorbent Assay (ELISA) both in patients and in controls.

Results: Phenotypical analysis of PB samples revealed that T lymphocytes are significantly increased in ROHHADNET patients, compared to obese controls (cells/µl, mean±SD:1859±450,5 vs 1544±441,8, P=0.04) with a prevalence of CD4-T cells (1129±394,4 vs 749,3±316,2, P=0.03) and a lower number of activated CD8-T cells (90,90±47,15 vs 204,1±113,1, P=0.02). Considering regulatory cell subsets, patients displayed an increase of regulatory B cells (Breg) (30,61±11,75 vs 19,07±14,44, P=0.05) and a significantly increased Type-1 regulatory T cell subset (Tr1) (4,880±2,740 vs 2,205±1,735, P=0.03). Among CD8-T cells, we observed a lower number of T effector memory (TEM) (20,56±15,15 vs 57,66±35,47, P=0.02) in patients than in controls. In contrast, among CD4-T cells, we observed higher number of T naïve (826,1±413,9 vs 383,1±304,1 P=0.04) and T effector (TEFF) (34,32±26,53 vs7,59±3,82, P=0.0008) in ROHHAD(NET) patients. Furthermore, in ROHHAD(NET) patients, we found a significantly increased serum level of IL-8 (Pg/ml, mean±SDS:58,35±120,7 vs 30,03±72,43, P=0.008) and MCP-1(86,91±68,74 vs 28,15±16,59, P=0.01). No differences were shown in other chemokines tested (IP-10, MIG and RANTES). Finally, sHLA-G was significantly lower in ROHHAD(NET) vs controls (ng/ml:1,31±3,09 vs 9,56±14,83, P=0.03), whereas sHLA-E concentration was similar between the two groups.

Conclusions: In agreement with published data, our findings seem to support the immune-dysregulation hypothesis in ROHHAD(NET) syndrome in comparison to simple obesity. If these assumptions are confirmed by larger and multicentric studies, there might be a rationale for therapeutic trials with immunosuppressors or immunomodulators in this syndrome.