RESUMO
BACKGROUND AND OBJECTIVES: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population. METHODS: We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls. RESULTS: Our genome-wide association analysis identified a strong association at the IFIH1 locus on chromosome 2q24.2 (rs3747517, p = 1.06 × 10-8, OR = 1.55, 95% CI, 1.34-1.80), outside of the human leukocyte antigen (HLA) region. Furthermore, through a fine-mapping study of the MHC region, we discovered associations for 3 specific HLA class I and II alleles. Notably, HLA-DQB1*05:02 (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59) demonstrates the strongest association among classical HLA alleles, closely followed by HLA-A*11:01 (p = 4.36 × 10-7; OR, 1.52; 95% CI 1.29-1.79) and HLA-A*02:07 (p = 1.28 × 10-8; OR, 1.87; 95% CI 1.50-2.31). In addition, we uncovered 2 main HLA amino acid variation associated with anti-NMDAR encephalitis including HLA-DQß1-126H (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59), exhibiting a predisposing effect, and HLA-B-97R (p = 3.40 × 10-8; OR, 0.63; 95% CI 0.53-0.74), conferring a protective effect. Computational docking analysis suggested a close relationship between the NR1 subunit of NMDAR and DQB1*05:02. DISCUSSION: Our findings indicate that genetic variation in IFIH1, involved in the type I interferon signaling pathway and innate immunity, along with variations in the HLA class I and class II genes, has substantial implications for the susceptibility to anti-NMDAR encephalitis in the Chinese Han population.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Cadeias beta de HLA-DQ , Helicase IFIH1 Induzida por Interferon , Humanos , Encefalite Antirreceptor de N-Metil-D-Aspartato/genética , Estudo de Associação Genômica Ampla , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/genética , Antígenos HLA-A/genética , Cadeias beta de HLA-DQ/genética , Helicase IFIH1 Induzida por Interferon/genéticaRESUMO
Inflammatory myofibroblastic tumor (IMT) in the liver is an uncommon lesion of uncertain pathogenesis. In most cases, symptomatological imaging and clinical studies suggest malignancy. We report a case of liver IMT with imaging findings from positron emission tomography/computed tomography (PET/CT), contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasonography (CEUS). This report was the first to depict a PET/CT scan of a liver IMT that revealed an inhomogeneous, intense (fluorine 18)-fluoro-2-deoxy-D-glucose uptake. The CECT and CEUS images showed a hepatic artery supplying blood to the mass and necrosis. The characteristic histopathological features and the presence of spindle cells expressing smooth muscle actin, collagen fibers and lymphocytes allowed for the diagnosis of liver IMT. Recognizing such findings will help to achieve a correct diagnosis and may prevent inappropriate treatment.