Daniel Briac, Acquaviva Eric, Bader-Meunier Brigitte, Belot Alexandre, Dingulu Glory, Dumaine Cecile, Faye Albert, Frémond Marie-Louise, Lavialle Laura, Meinzer Ulrich, Quartier Pierre, Vinit Caroline, Delorme Richard, Melki Isabelle, Ellul Pierre
Excellence Centre for Autism & Neuro-developmental Disorders, Department of Child and Adolescent Psychiatry, APHP, Robert Debré Hospital, Université Paris-Cité, Boulevard Sérurier, Paris, France.
Pediatric Hematology-Immunology and Rheumatology Department, AP-HP, and Reference centre for inflammatory Rheumatism, AutoImmune disease and Systemic interferonopathies in childrEn (RAISE), Hôpital Necker-Enfants Malades, Université Paris-Cité, Paris, France.
Pediatr Rheumatol Online J. 2025 Jun 2;23(1):62. doi: 10.1186/s12969-025-01103-5.
The immune system is physiologically involved in brain development and homeostasis. Consequently, early immune-mediated events are known risk factors for neurodevelopmental disorders (NDD). We recently found that early systemic autoimmune and autoinflammatory disorders (ESAID) are associated with an increased risk of neurodevelopmental disorders due to the direct impact of inflammation on brain development. However not all ESAID patient will develop NDD. In this study, we aimed to better characterized the natural history of the NDD comorbidity and investigate the influence of others NDD risk factors in ESAID patients with ADHD (ESAID+/ADHD+; n = 14) compared to patient with ESAID without ADHD (ESAID+/ADHD-; n = 14) and patient with ADHD without ESAID (ESAID-/ADHD + = 35).
We did a case control study using a cohort of ESAID patients (ARTEMIS) and an ADHD cohort (Robert Debre) and found that the onset of ADHD in patients with ESAID is associated with global cognitive brain impairment that does not appear to be due to shared genetic risk factors, reinforcing the hypothesis of an immune-mediated mechanism. Regarding the etiopathogenesis of this comorbidity, we found that low birth weight, a known risk factor for NDD, contributes to the development of ADHD in ESAID patients.
Pediatricians, and in particular pediatric rheumatologists, need to be aware of the frequency of ADHD-related comorbidities in ESAID patients. They should therefore systematically look for NDD in ESAID patients, particularly in cases of low birth weight. Early detection and management of NDD is the only way to limit its impact on morbidity and life trajectory.
免疫系统在大脑发育和内环境稳定中发挥着生理作用。因此，早期免疫介导的事件是神经发育障碍（NDD）的已知危险因素。我们最近发现，早期全身性自身免疫性和自身炎症性疾病（ESAID）由于炎症对大脑发育的直接影响，与神经发育障碍风险增加有关。然而，并非所有ESAID患者都会发展为NDD。在本研究中，我们旨在更好地描述NDD合并症的自然病史，并调查其他NDD危险因素对患有注意力缺陷多动障碍（ADHD）的ESAID患者（ESAID+/ADHD+；n = 14）的影响，与没有ADHD的ESAID患者（ESAID+/ADHD-；n = 14）和没有ESAID的ADHD患者（ESAID-/ADHD+ = 35）进行比较。
我们使用一组ESAID患者队列（ARTEMIS）和一个ADHD队列（Robert Debre）进行了病例对照研究，发现ESAID患者中ADHD的发作与整体认知脑损伤有关，这似乎不是由于共同的遗传危险因素所致，这强化了免疫介导机制的假设。关于这种合并症的病因，我们发现低出生体重是NDD的已知危险因素，它促成了ESAID患者中ADHD的发展。
儿科医生，尤其是儿科风湿病学家，需要意识到ESAID患者中与ADHD相关合并症的发生率。因此，他们应该系统地在ESAID患者中寻找NDD，特别是在低出生体重的情况下。NDD的早期检测和管理是限制其对发病率和生命轨迹影响的唯一方法。
