Blood Lymphocyte Subsets and Proinflammatory Cytokine Profile in ROHHAD(NET) and non-ROHHAD(NET) Obese Individuals

Daniela Fava; Fabio Morandi; Ignazia Prigione; Alessia Angelelli; Paola Bocca; Angela Pistorio; Stefano Volpi; Giuseppa Patti; Carlotta Pepino; Emilio Casalini; Anna Elsa Maria Allegri; Natascia Di Iorgi; Giuseppe d'Annunzio; Flavia Napoli; Mohamad Maghnie

doi:10.1210/jendso/bvad103

Blood Lymphocyte Subsets and Proinflammatory Cytokine Profile in ROHHAD(NET) and non-ROHHAD(NET) Obese Individuals

J Endocr Soc. 2023 Aug 3;7(9):bvad103. doi: 10.1210/jendso/bvad103. eCollection 2023 Aug 1.

Authors

Daniela Fava^{1

2}, Fabio Morandi³, Ignazia Prigione⁴, Alessia Angelelli¹, Paola Bocca⁴, Angela Pistorio⁵, Stefano Volpi^{1

4}, Giuseppa Patti^{1

2}, Carlotta Pepino¹, Emilio Casalini¹, Anna Elsa Maria Allegri², Natascia Di Iorgi^{1

2}, Giuseppe d'Annunzio², Flavia Napoli², Mohamad Maghnie^{1

2}

Affiliations

¹ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16132 Genoa, Italy.
² Department of Pediatrics, Pediatric Endocrinology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.
³ UOSD Cell Factory, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.
⁴ Center for Autoinflammatory Diseases and Immunodeficiencies, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.
⁵ Scientific Direction, Epidemiology and Biostatistics Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.

Abstract

Context: Rapid-onset obesity with central hypoventilation, hypothalamic dysfunction, and autonomic dysregulation with neural crest tumors (ROHHAD-NET) syndrome pathophysiology remains elusive. Acquired neuroimmunological dysfunction has been proposed as a possible pathogenetic pathway.

Objective: The aim of our study was to characterize lymphocyte subpopulations subsets in peripheral blood (PB) and to evaluate a panel of proinflammatory cytokines/chemokines in ROHHAD(NET) patients vs controls.

Methods: We included 11 ROHHAD(NET) patients, 7 ROHHAD and 4 ROHHAD-NET, selected by clinical criteria. Controls were 11 simple obese children, matched for age and sex. Flow cytometric analysis and enzyme-linked immunosorbent assay were performed on PB and serum samples of the 2 groups.

Results: Analysis revealed that T lymphocytes are significantly increased in ROHHAD(NET) patients (P = .04) with a prevalence of CD4-T cells (P = .03) and a lower number of activated CD8-T cells (P = .02). With regard to regulatory subset, patients displayed increased regulatory B cells (P = .05) and type-1 regulatory T cells (P = .03). With regard to CD8-T cells, a lower number of T effector memory was observed (P = .02). In contrast, among CD4-T cells, we found a higher number of T naive (P = .04) and T effector (P = .0008). Interleukin-8 (IL-8) levels and monocyte chemotactic protein-1 were increased in patients vs controls (P = .008 and P = .01, respectively). Furthermore, IL-8 levels were higher in the subgroup with neural tumor (P = .0058) (ROHHAD-NET) than in patients without neural tumor (ROHHAD). Soluble HLA-G was significantly lower in patients vs controls (P = .03).

Conclusion: Our findings contribute to support the hypothesis of immune dysregulation, which may underlie this complex, often fatal disease. Because ROHHAD(NET) syndrome is an ultra-rare disease, multicentric studies are needed to improve the effect of our data in the management of this condition.

Keywords: ROHHAD; ROHHAD-NET; chemokines; cytokines; immune phenotype.