BackgroundGiven their similar appearance and histology, halo nevi (HN) were considered as a type of vitiligo. However, whether HN have stronger immune response than stable vitiligo (VL) remains unclear. In addition, the molecular alterations in HN compared with normal nevocytic nevi (NN) and primary cutaneous melanoma (MM) must be determined. This study aimed to systematically characterize the molecular immunological features of HN.MethodsSkin samples from patients with HN, VL, NN, and MM were obtained with informed consent. Each of the four groups underwent transcriptome sequencing and data analysis were for pairwise comparison. Quantitative real-time PCR (RT-qPCR) was conducted to confirm the transcriptional expression of some differentially expressed genes (DEGs) that were closely related to immunity.ResultsA total of 441 and 1507 DEGs were found in the HN/NN and HN/MM groups, respectively. Compared with those of VL, HN lesions contained 162 up-regulated DEGs and 12 down-regulated DEGs. Bioinformatics analysis showed that the up-regulated genes in HN were substantially enriched in immune response, immune deficiency, and immune rejection; biological stimulation (virus, bacteria); and proliferation and activation of immune cells. Immune cell composition analysis also confirmed high expression levels of multiple immunocytes in HN.ConclusionThe molecular immune mechanisms of HN and VL were similar, but the immune activity of HN was stronger than that of VL. Innate and adaptive immunity were involved in the pathogenesis and progression of HN and VL.