Min Zhang, YiRan Wu, ZhaoXu Lu, MeiYan Song, XiaoLan Huang, LaLa Mi, Jian Yang, Xiaodai Cui. Clin Psychopharmacol Neurosci 2023;21:240-51. https://doi.org/10.9758/cpn.2023.21.2.240

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical manifestations and the pathogenesis of SLE is still unclear. Various omics results have been reported for SLE, but the molecular hallmarks of SLE, especially in patients with different disease activity, using an integrated multi-omics approach have not been fully investigated. Here, we collected blood samples from 10 healthy controls (HCs) and 40 SLE patients with different clinical activity including inactive (IA), low activity (LA), and high activity (HA). Using an integrative analysis of proteomic, metabolomic and lipidomic profiles, we report the multi-omics landscape for SLE. The molecular changes suggest that both the complement system and the inflammatory response were activated in SLEs and were associated with disease activity. Additionally, activation of the immunoglobulin mediated immune response were observed in the LA stage of the disease, however this immune response was suppressed slightly in the HA stage. Finally, an imbalance in lipid metabolism, especially in sphingolipid metabolism, accompanied with dysregulated apolipoproteins were observed to contribute to the disease activity of SLE. The multi-omics data presented in this study and the characterization of peripheral blood from SLE patients may thus help provide important clues regarding the pathogenesis of SLE.

Background: Langerhans cell histiocytosis (LCH) is a rare neoplastic disease that occurs in both children and adults, and BRAF V600E is detected in up to 64% of the patients. Several studies have discussed the associations between BRAF V600E mutation and clinicopathological manifestations, but no clear conclusions have been drawn regarding the clinical significance of the mutation in pediatric patients. Results: We retrieved the clinical information for 148 pediatric LCH patients and investigated the BRAF V600E mutation using next-generation sequencing alone or with droplet digital PCR. The overall positive rate of BRAF V600E was 60/148 (41%). The type of sample (peripheral blood and formalin-fixed paraffin-embedded tissue) used for testing was significantly associated with the BRAF V600E mutation status (p-value = 0.000 and 0.000). The risk of recurrence declined in patients who received targeted therapy (p-value = 0.006; hazard ratio 0.164, 95%CI: 0.046 to 0.583). However, no correlation was found between the BRAF V600E status and gender, age, stage, specific organ affected, TP53 mutation status, masses close to the lesion or recurrence. Conclusions: This is the largest pediatric LCH study conducted with a Chinese population to date. BRAF V600E in LCH may occur less in East Asian populations than in other ethnic groups, regardless of age. Biopsy tissue is a more sensitive sample for BRAF mutation screening because not all of circulating DNA is tumoral. Approaches with low limit of detection or high sensitivity are recommended for mutation screening to avoid type I and II errors.

Variants in NAA15 are closely related to neurodevelopmental disorders (NDDs). In this study, we investigated the spectrum and clinical features of NAA15 variants in a Chinese NDD cohort of 769 children. Four novel NAA15 pathogenic variants were detected by whole-exome sequencing, including three de novo variants and one maternal variant. The in vitro minigene splicing assay confirmed one noncanonical splicing variant (c.1410+5G>C), which resulted in abnormal mRNA splicing. All affected children presented mild developmental delay, and catch-up trajectories were noted in three patients based on their developmental scores at different ages. Meanwhile, the literature review also showed that half of the reported patients with NAA15 variants presented mild/moderate developmental delay or intellectual disability, and possible catch-up sign was indicated for three affected patients. Taken together, our study expanded the spectrum of NAA15 variants in NDD patients. The affected patients presented mild developmental delay, and possible catch-up developmental trajectories were suggested. Studying the natural neurodevelopmental trajectories of NDD patients with pathogenic variants and their benefits from physical rehabilitations are needed in the future for precise genetic counseling and clinical management.