Fava Daniela, Morandi Fabio, Prigione Ignazia, Angelelli Alessia, Bocca Paola, Pistorio Angela, Volpi Stefano, Patti Giuseppa, Pepino Carlotta, Casalini Emilio, Allegri Anna Elsa Maria, Di Iorgi Natascia, d'Annunzio Giuseppe, Napoli Flavia, Maghnie Mohamad
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, 16132 Genoa, Italy.
Department of Pediatrics, Pediatric Endocrinology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.
J Endocr Soc. 2023 Aug 3;7(9):bvad103. doi: 10.1210/jendso/bvad103. eCollection 2023 Aug 1.
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.
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.
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.
Analysis revealed that T lymphocytes are significantly increased in ROHHAD(NET) patients ( = .04) with a prevalence of CD4-T cells ( = .03) and a lower number of activated CD8-T cells ( = .02). With regard to regulatory subset, patients displayed increased regulatory B cells ( = .05) and type-1 regulatory T cells ( = .03). With regard to CD8-T cells, a lower number of T effector memory was observed ( = .02). In contrast, among CD4-T cells, we found a higher number of T naive ( = .04) and T effector ( = .0008). Interleukin-8 (IL-8) levels and monocyte chemotactic protein-1 were increased in patients vs controls ( = .008 and = .01, respectively). Furthermore, IL-8 levels were higher in the subgroup with neural tumor ( = .0058) (ROHHAD-NET) than in patients without neural tumor (ROHHAD). Soluble HLA-G was significantly lower in patients vs controls ( = .03).
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.
快速进展性肥胖伴中枢性低通气、下丘脑功能障碍及神经嵴肿瘤相关自主神经失调（ROHHAD-NET）综合征的病理生理学仍不清楚。获得性神经免疫功能障碍被认为是一种可能的发病机制。
我们研究的目的是对ROHHAD（NET）患者外周血中的淋巴细胞亚群进行特征分析，并评估一组促炎细胞因子/趋化因子在ROHHAD（NET）患者与对照组中的情况。
我们纳入了11例根据临床标准选取的ROHHAD（NET）患者，其中7例ROHHAD患者和4例ROHHAD-NET患者。对照组为11名年龄和性别匹配的单纯肥胖儿童。对两组的外周血和血清样本进行流式细胞术分析和酶联免疫吸附测定。
分析显示，ROHHAD（NET）患者的T淋巴细胞显著增加（P = 0.04），以CD4-T细胞为主（P = 0.03），活化的CD8-T细胞数量较少（P = 0.02）。关于调节亚群，患者的调节性B细胞增加（P = 0.05），1型调节性T细胞增加（P = 0.03）。关于CD8-T细胞，观察到效应记忆T细胞数量较少（P = 0.02）。相反，在CD4-T细胞中，我们发现幼稚T细胞数量较多（P = 0.04），效应T细胞数量较多（P = 0.0008）。与对照组相比，患者的白细胞介素-8（IL-8）水平和单核细胞趋化蛋白-1增加（分别为P = 0.008和P = 0.01）。此外，有神经肿瘤的亚组（ROHHAD-NET）中的IL-8水平高于无神经肿瘤的患者（ROHHAD）（P = 0.0058）。患者的可溶性人类白细胞抗原G显著低于对照组（P = 0.03）。
我们的研究结果有助于支持免疫失调的假说，这可能是这种复杂且通常致命疾病的基础。由于ROHHAD（NET）综合征是一种极为罕见的疾病，需要多中心研究来提高我们的数据在这种疾病管理中的作用。
