Proteomic Analysis Reveals Oxidative Phosphorylation and JAK-STAT Pathways Mediated Pathogenesis of Pemphigus Vulgaris.

Pemphigus vulgaris (PV) stands as a rare autoimmune bullous disease, while the precise underlying mechanism remains incompletely elucidated. High-throughput proteomic methodologies, such as LC-MS/MS, have facilitated the quantification and characterisation of proteomes from clinical skin samples, enhancing our comprehension of PV pathogenesis. The objective of this study is to elucidate the signalling mechanisms underlying PV through proteomic analysis. Proteins and cell suspension were extracted from skin biopsies obtained from both PV patients and healthy volunteers and subsequently analysed using LC-MS/MS and scRNA-seq. Cultured keratinocytes were treated with PV serum, followed by an assessment of protein expression levels using immunofluorescence and western blotting. A total of 880, 605, and 586 differentially expressed proteins (DEPs) were identified between the lesion vs. control, non-lesion vs. control, and lesion vs. non-lesion groups, respectively. The oxidative phosphorylation (OXPHOS) pathway showed activation in PV. Keratinocytes are the major cell population in the epidermis and highly expressed ATP5PF, ATP6V1G1, COX6B1, COX6A1, and NDUFA9. In the cellular model, there was a notable increase in the expression levels of OXPHOS-related proteins (V-ATP5A, III-UQCRC2, II-SDHB, I-NDUFB8), along with STAT1, p-STAT1, and p-JAK1. Furthermore, both the OXPHOS inhibitor metformin and the JAK1 inhibitor tofacitinib demonstrated therapeutic effects on PV serum-induced cell separation, attenuating cell detachment. Metformin notably reduced the expression of V-ATP5A, III-UQCRC2, II-SDHB, I-NDUFB8, p-STAT1, p-JAK1, whereas tofacitinib decreased the expression of p-STAT1 and p-JAK1, with minimal impact on the expression of V-ATP5A, III-UQCRC2, II-SDHB, and I-NDUFB8. Our results indicate a potential involvement of the OXPHOS and JAK-STAT1 pathways in the pathogenesis of PV.

TMEM52B Isoforms P18 and P20 Differentially Promote the Oncogenesis and Metastasis of Nasopharyngeal Carcinoma.

Transmembrane protein 52B (TMEM52B), a newly identified tumor-related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B-P18 and TMEM52B-P20, differing in their N-terminals. While both isoforms exhibit similar pro-oncogenic roles and contribute to drug resistance in NPC, TMEM52B-P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B-P18 is confined to the cytoplasm, while TMEM52B-P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane-localized TMEM52B-P20 promotes E-cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B-P18 and TMEM52B-P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis.

A case report of dermatomyositis mimicking myasthenia gravis.

RATIONALE: Patients who have myasthenia gravis or dermatomyositis show clinical signs of muscular weakening. Ocular muscle involvement is uncommon, and symmetrical proximal limb weakness is the typical presentation of dermatomyositis. However, the earliest and most noticeable sign in those with myasthenia gravis is extraocular muscular paralysis. Dermatomyositis is frequently complicated by malignancy, and the common malignancies associated with dermatomyositis vary by region and ethnicity, while thymoma is relatively rare. About 10% to 15% of people with myasthenia gravis have thymoma, which is involved in the etiology of the disease. PATIENT CONCERNS: A 68-year-old female presented with ocular muscle weakness for 10 days that manifested as bilateral blepharoptosis with the phenomenon of "light in the morning and heavy in the evening." Imaging examination showed anterior mediastinal thymic tumor with metastasis. DIAGNOSES: After a thorough physical examination, we discovered bilateral upper limbs with grade IV muscle strength and the typical rash of dermatomyositis. In combination with elevated serum kinase levels and electromyography suggesting myogenic damage, the patient was finally diagnosed as dermatomyositis with multiple metastases of thymoma. INTERVENTIONS: The patient received oral hydroxychloroquine sulfate, topical corticosteroids, and tacrolimus ointment, but these did not work very well. Subsequently, the patient underwent surgery combined with radiotherapy for the thymoma. OUTCOMES: Muscle weakness in the patient improved after effective treatment of tumor, and the rash mostly disappeared. CONCLUSION: Ocular muscle weakness and thymoma are more common in myasthenia gravis, but we cannot ignore the possibility of dermatomyositis. To further establish the diagnosis, a thorough physical examination and laboratory findings are required. Further tumor screening should be performed for patients with dermatomyositis. Early detection and management of possible tumors are essential to the treatment of dermatomyositis linked to malignancies.

[Clinical analysis of the treatment of maxillary odontogenic cyst by nasal endoscope fenestration through nasal base].

Objective:To investigate the feasibility and clinical effect of the surgical approach and method of transnasal fenestration under nasal endoscope for the treatment of maxillary odontogenic cyst. Methods:The clinical data of 23 cases with maxillary odontogenic cysts treated by nasal endoscopy through nasal fenestration were retrospectively analyzed. All cases underwent nasal endoscopy and CT examination before the operation. The mucosal membrane of the parietal wall of the cyst was excised through fenestration of the nasal base. The cyst fluid was removed by decompression, and the bony opening of the nasal base was trimmed and enlarged to the edge of the cyst. The intraoperative and postoperative effects were observed. Results:All cases were well exposed under the direct vision of nasal endoscope. The top wall of the cyst was removed to maximize the communication between the cyst cavity and the nasal floor. There were no complications such as nasolacrimal duct injury, turbinate atrophy, necrosis, and facial numbness. All patients were followed up for 6-12 months, and the clinical symptoms gradually disappeared after surgery. The inferior turbinate was in good shape, the cyst cavity was smooth, the cyst wall was determined, and no cyst recurrence was observed. Conclusion:The treatment of odontogenic cyst of maxilla under nasal endoscope through nasal fenestration is convenient. It has less trauma, fewer complications and a satisfactory curative effect, which is worthy of clinical promotion.

Clinical and economic benefits of image-guided system in functional endoscopicsinus surgery: a retrospective chart review study in China.

BACKGROUND: Image-guided system (IGS) has been gradually applied in the field of rhinology, making functional endoscopic sinus surgery (FESS) a truly minimally invasive and precise surgery. This study was based on real-world data from China hospitals and aimed to evaluate the clinical and economic benefits of the IGS navigation system in FESS. METHODS: This was a two-center retrospective chart review of patients with chronic rhinosinusitis who underwent FESS, including open frontal sinus between July 1, 2018 and December 31, 2019 in China. The intervention group consisted of 100 patients who underwent FESS with the IGS navigation system (IGS group), and the control group consisted of 100 patients who underwent conventional FESS (Non-IGS group). Data were collected from surgical notes and hospital medical records. The primary endpoints for clinical effectiveness and safety were avoid rehospitalization due to bleeding, avoid reoperation due to bleeding, and avoid reoperation due to recurrence. RESULTS: There were no cases of rehospitalization due to bleeding, reoperation due to bleeding, and reoperation due to recurrence in the IGS group, with an avoidance rate of 100%. In the non-IGS group, there were four cases of rehospitalization and reoperation due to bleeding, with an avoidance rate 96.00% (P = 0.121). No cases of reoperation due to recurrence were in the non-IGS group. The total hospitalization cost was 17,391.51 CNY in the IGS group and 17,742.41 CNY in the non-IGS group per patient, with no statistical difference between the two groups (P = 0.715). Compared with the non-IGS group, the IGS group had an overall cost saving of 350.90 CNY per patient. Although the procedure-related medical costs of IGS group were increased by 1,286.12 CNY compared with the non-IGS group, this was more than offset by other costs. CONCLUSION: The results of the study indicated that the IGS may avoid occurrence of rehospitalization and reoperation due to postoperative bleeding. Although the use of navigation technology increased the cost of surgery, its clinical effectiveness brought other medical cost savings, resulting in no significant difference in the overall cost of navigation surgery compared to conventional surgery. The IGS should be considered cost-effectiveness in the treatment of FESS.

Bullous Pemphigoid After Vaccination With the Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine: Two Cases in China.

BACKGROUND: Coronavirus disease-2019 (COVID-19) led to a global pandemic in March 2020 that has involved tens of millions of people. To date, prophylactic vaccines have been found to be the most effective method to contain the pandemic. Bullous pemphigoid (BP) is an autoimmune skin disease that mainly affects older individuals. CASE REPORTS: The authors report 2 confirmed cases of BP in patients with history of cerebral infarction who received the inactivated severe acute respiratory syndrome coronavirus 2 vaccine. A 67-year-old woman was hospitalized for a generalized rash that appeared 7 days after the first dose of inactivated COVID-19 vaccine. The rash was aggravated after the second dose. The second patient was a 66-year-old woman who was hospitalized for a generalized rash that appeared 10 days after the first dose of inactivated COVID-19 vaccine. There were no abnormalities in the baseline blood tests. Laboratory and histologic examinations confirmed the diagnosis of BP. The patients were treated with systemic glucocorticoids, antibiotics, topical corticosteroids, and emollients, which resulted in a significant reduction in pruritus and regression of lesions after 2 weeks. CONCLUSION: Two patients with a genetic background of HLA-DQB1*0302 had BP after vaccination in China. However, there is not enough evidence to indicate a requirement for genetic screening before receiving inactivated severe acute respiratory syndrome coronavirus 2 vaccines.

OFF-State Leakage Suppression in Vertical Electron-Hole Bilayer TFET Using Dual-Metal Left-Gate and N+-Pocket.

In this paper, an In0.53Ga0.47As electron-hole bilayer tunnel field-effect transistor (EHBTFET) with a dual-metal left-gate and an N+-pocket (DGNP-EHBTFET) is proposed and systematically studied by means of numerical simulation. Unlike traditional transverse EHBTFETs, the proposed DGNP-EHBTFET can improve device performance without sacrificing the chip density, and can simplify the manufacturing process. The introduction of the dual-metal left-gate and the N+-pocket can shift the point-tunneling junction and adjust the energy band and the electric field in it, aiming to substantially degrade the OFF-state current (IOFF) and maintain good ON-state performance. Moreover, the line tunneling governed by the tunneling-gate and the right-gate can further regulate and control IOFF. By optimizing various parameters related to the N+-pocket and the gate electrodes, DGNP-EHBTFET's IOFF is reduced by at least four orders of magnitude, it has a 75.1% decreased average subthreshold swing compared with other EHBTFETs, and it can maintain a high ON-state current. This design greatly promotes the application potential of EHBTFETs.

Effect of multifunctional laser photoelectricity platform combined with hydroxychloroquine treatment sensitive facial skin.

To observe the clinical efficacy of a multifunctional laser photoelectric platform combined with hydroxychloroquine in the treatment of l sensitive facia skin. A total of 226 patients with sensitive facial skin treated from March 2019 to November 2021 were randomly divided into two groups. Both groups were given an external moisturizer (shumin moisturizer) once in the morning and once in the evening as basic skin care treatment for the disease. The control group received hydroxychloroquine sulfate tablets (0.2 g), twice a day; The observation group was treated with multifunctional laser photoelectric platform combined with hydroxychloroquine orally, and the clinical effects of the two groups were compared. The effective rates of the observation group were 48.67%, 73.45%, and 93.80% at the first, second and fourth weekend of treatment, respectively, which were significantly higher than those of the control group (15.93%, 30.97%, and 38.93%, respectively), with statistical significance (p < 0.05). On the basis of skin care with an external moisturizer, using a multifunctional laser photoelectric platform combined with hydroxychloroquine can significantly improve the clinical efficacy of facial sensitive skin, superior to hydroxychloroquine alone, with high safety and worthy of clinical application.

The Effect of Eco-Friendly Inhibitors on the Corrosion Properties of Concrete Reinforcement in Harsh Environments.

In the present research, the synergistic effect of Arabic and guar gum inhibitors on the corrosion efficiency of concrete reinforcement was investigated. Thus, eight types of Arabic and guar gum combinations with 100, 250, 500, 750, and 1000 ppm were added to the steel reinforcement for 1, 7, 28, 48, and 72 days. The corrosion behavior of the samples was investigated by the electrochemical impedance (EIS) test. Water transmissibility, electrical resistivity, and compressive strength of concrete were also studied. The results showed that adding inhibitors generally increased the compressive strength of concrete. It was also found that water transmissibility was reduced by the addition of inhibitors. The electrical resistivity of the samples increased slightly with increasing time up to 72 days. EIS and Tafel results have demonstrated that Arabic and guar gums are effective inhibitors for reinforced concrete structures. Furthermore, scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) utilized to analyze the samples indicated that inhibitor grain size was enhanced by enhancing the concentration of the inhibitor combination, showing that the guar and Arabic inhibitor combinations were properly absorbed on the reinforcement surface. Results showed that a sample with 250 ppm Arabic gum and 250 ppm guar gum having a properly distributed inhibitor combination on the reinforcement surface creates a desirable cathode current.

Combined microbiome and metabolome analysis of gut microbiota and metabolite interactions in chronic spontaneous urticaria.

Background: The pathogenesis of chronic spontaneous urticaria (CSU) is unclear, and it turned out to be involved in biological processes, such as autoimmunity, autoallergy, inflammation, and coagulation. The gut microbiota plays an important role in immune and inflammatory diseases. However, the relationship between chronic spontaneous urticaria and the gut microbiota remains unknown. Methods: The stool and serum samples were taken from 15 CSU patients and 15 normal controls. Changes in the composition of gut microbiota and serum metabolism in CSU patients and normal controls were analyzed by 16S ribosomal RNA (rRNA) gene sequencing and untargeted metabolomics. Results: The results of 16S rRNA gene sequencing showed that compared with normal controls, CSU patients had increased α-diversity of gut microbiota and significant differences in ß-diversity. At the phylum level, the relative abundance of Firmicutes increased and the relative abundance of Bacteroidetes and Proteobacteria decreased in CSU patients compared with healthy controls. At the genus level, six kinds of bacteria were significantly enriched in CSU patients and five in normal controls. Metabolomic analysis revealed altered levels of metabolites such as unsaturated fatty acids and purines. Correlation analysis of gut microbiota and metabolites showed that Lachnospira was negatively correlated with arachidonic acid, and Gemmiger was also negatively correlated with (±)8-HETE. Conclusion: This study suggests that changes in gut microbiota and metabolites may play a role in immune and inflammatory pathways in the pathogenesis of CSU patients.

LncRNA HOXC-AS1 promotes nasopharyngeal carcinoma (NPC) progression by sponging miR-4651 and subsequently upregulating FOXO6.

The incidence rate of nasopharyngeal carcinoma (NPC) is the highest among the malignant tumors of otorhinolaryngology, posing a huge burden to public health. Long noncoding RNAs (lncRNAs) exert an important role in tumorigenesis and the progression of various cancers. The present study found that HOXC-AS1 was highly expressed in NPC and in NPC cell lines, suggesting a critical role of HOXC-AS1 in NPC progression. In addition, the abundance of HOXC-AS1 was negatively correlated with the prognosis of NPC. To molecularly dissect the mechanism of HOXC-AS1 in NPC progression, we knocked down the expression of HOXC-AS1 in HNE1 and C666-1 cells. Then, we employed CCK8, colony-formation experiment and Transwell to investigate how the cell performed when HOXC-AS1 was knocked down. It could be observed that HOXC-AS1 knockdown decreases cell proliferation, migration and invasion, but induces cell apoptosis in NPC. We found that HOXC-AS1 could sponge miR-4651 subsequently binding FOXO6 and inhibiting its expression. Therefore, HOXC-AS1/miR-4651/FOXO6 may form a competing endogenous RNA (ceRNA) network that promotes NPC progression. In conclusion, our study demonstrates that HOXC-AS1 promotes NPC progression by sponging miR-4651 and regulating FOXO6 expression, thus providing potential pharmaceutical targets for developing new NPC treatments.

Treatment of Recurrent Undifferentiated Pleomorphic Sarcoma of Infratemporal Fossa by Surgery Combined With Carbon Ion Radiotherapy: One Case Report.

We retrospectively analyzed the diagnosis and treatment process of one patient with recurrent undifferentiated pleomorphic sarcoma (UPS) of infratemporal fossa and made a definite diagnosis by combining the imaging and pathological examination results. After treatment failure with 2 cycles of chemotherapy and several surgeries, UPS was eventually treated by surgery + carbon ion radiotherapy, and MRI reexamination showed no relapse. Head and neck UPS is located deeply, easily recurs after operation, and difficult to be resected completely by surgery, with a gradually shortened interval of relapse over the number of surgeries, which becomes a treatment challenge. After the last surgery, the patient received carbon ion radiotherapy, with a good therapeutic effect, and no sign of relapse just before sending this article. Based on the above advantages, we have concluded that surgery + carbon ion radiotherapy is a new effective pathway to treat head and neck UPS.

[Functional nasolacrimal duct decompression for chronic dacryocystitis].

Objective:To investigate the feasibility of endoscopic nasolacrimal decompression for chronic dacryocystitis. Method:22 patients with chronic dacryocystitis hospitalized at Longgang ENT hospital were participated in this study. An injection of 30% iohexol was administered to conduct lacrimal sac angiography. The injection was stopped when the agent reflux from the lacrimal duct, and a computed tomography（CT） scan of the lacrimal duct was performed immediately. Sinuses Trachea Isoftware was used to reconstruct a three-dimensional（3D） view of the lacrimal passage and its surrounding structures. The software was used to simulate the "cutting" of the lacrimal sac and nasolacrimal duct; the lacrimal sac and nasal lacrimal duct were removed after 1/2-3/4 circumferences to decompress the passage and expose the membranous nasolacrimal duct. CT scans were performed on ten adult frozen cadaveric heads, and the nasolacrimal duct decompression operation was simulated. Then, the bone of the nasolacrimal duct was removed, membranous nasolacrimal duct was exposed, and the capsular nasolacrimal duct was dilated. Result:①The lacrimal angiography study revealed that lacrimal duct obstruction occurred in the nasolacrimal duct segment, accounting for 72.7%（16/22） of the study cases. ② The anatomical examination showed that the outer sidewall of the nasolacrimal duct was composed of the tear groove of the maxilla, and the inner wall was composed of the descending process of the lacrimal bone. ③ In cadaveric heads, decompression of the osseous nasolacrimal duct was performed, exposing the membranous nasolacrimal duct. ④ A balloon catheter could dilate the membranous nasolacrimal duct and allow the lacrimal passage to be flushed. Conclusion:Endoscopic nasolacrimal decompression preserves the integrity of the lacrimal duct, allows drainage of the lacrimal duct, and avoids obstruction of the lacrimal duct by preventing lacrimal granulation.

Direct Transcavernous Sinus Approach for Endoscopic Endonasal Resection of Intracavernous Sinus Tumors.

OBJECTIVE: Because of its vascular supply and neurovascular contents, the cavernous sinus (CS) is a challenging area to dissect in the setting of skull base tumors with intracavernous extension or invasion. In the present study, we report the clinical outcomes of 14 patients with tumors with CS invasion that were surgically treated using a direct transcavernous sinus approach for endoscopic endonasal resection of their intracavernous sinus tumors. METHODS: Fourteen patients had undergone surgery using a direct endoscopic endonasal transcavernous sinus approach. The pathologic entities included Knosp grade 3-4 pituitary adenomas (n = 8), meningioma (n = 3), squamous cell carcinoma (n = 2), and chondrosarcoma (n = 1). The indications, surgical technique, and outcomes are discussed. RESULTS: Gross total resection was achieved in 11 patients (78.6%). All patients experienced resolution or improvement of symptoms. One patient experienced a transient oculomotor nerve palsy, which had resolved within 2 months postoperatively. No other complications occurred. For those tumors that had been grossly resected, no recurrence developed in any patient (mean follow-up, 40.4 ± 24.8 months; range 10-84). CONCLUSIONS: Depending on the space created by intracavernous sinus tumors, use of the transanterior wall for the CS approach in endoscopic endonasal surgery could adequately treat most patients in our case series. This approach provided good visualization of the CS and can be used to treat tumors with favorable outcomes and a low incidence of complications in appropriately evaluated patients.

Fine mapping and subphenotyping implicates ADRA1B gene variants in psoriasis susceptibility in a Chinese population.

AIM: A genomic region on 5q33.3 lies between and encompasses the IL12B and PTTG1 genes, and contains many potential psoriasis causal variants. We aimed to further examine the influence of variants in and around this region. MATERIALS & METHODS: We used least absolute shrinkage and selection operator (LASSO)-based regression analysis to assess independent contributions of 2171 variants to psoriasis susceptibility and tested them for association with different clinical psoriasis subtypes. RESULTS: We found that ADRA1B gene variants contribute to psoriasis in Chinese population. ADRA1B gene variants have a stronger association with moderate-to-severe disease group and an earlier age at onset of psoriasis than IL-12B and PTTG1 variants. CONCLUSION: The association of variants in the ADRA1B gene with psoriasis could explain why variants in the IL-12B, ADRA1B and PTTG1 gene regions are associated with psoriasis.

Application of remifentanil combined with propofol in the diagnosis of colon cancer with awakening painless digestive endoscopy.

Anesthetic effect of remifentanil combined with propofol in awakening painless endoscopy was analyzed. Retrospective analysis of 120 cases of colon cancer were treated in Dongying People's Hospital from June 2015 to December 2017. All of them were treated by awakening painless digestive endoscopy, divided into 60 cases in observation group (combined with remifentanil and propofol anesthesia), and 60 cases in control group (combined intravenous anesthesia of finanib and propofol). The data were respectively recorded at time-points of oxygen inhalation, intubation for 10 min, awakening time, waking time, and the time-points for each represented as the time-points of T1, T2, T3, T4, T5 and recorded the diastolic blood pressure (DBP), respiratory rate (RR) and heart rate (HR), and compared the awakening effect and the occurrence of adverse reaction. There was no significant difference in the DBP index between the two groups at time-point T1 (P>0.05). The time-points of T2, T3, T4 and T5 were significantly different from the observation group (P<0.05). There was no significant difference in RR index between the two groups and between the same groups (P>0.05). Compared with the control group, the awakening time and consciousness recovering of the observation group is lower (P<0.05). The incidence of adverse reactions after awakening operation between the two groups was statistically significant (P<0.05). The local pain rate in the observation group after the awakening operation was lower than the control group. The combined use of trace remifentanil and small dose propofol in the awakening painless digestive endoscopy can make the patients with colon cancer more stable when they are in the awakening state, so as to improve the safety of awakening painless digestive endoscopy. It is worth promoting in clinical practice.

Association Study and Fine-Mapping Major Histocompatibility Complex Analysis of Pemphigus Vulgaris in a Han Chinese Population.

To identify possible additional genetic susceptibility loci for pemphigus vulgaris (PV), we performed a genome-wide association study of 240 PV patients and 1,031 control individuals, and we selected the top single nucleotide polymorphisms for replication in independent samples, with 252 patient samples and 1,852 control samples. We identified rs11218708 (P = 3.1 × 10-8, odds ratio = 1.54) at chromosome locus 11q24.1 as significantly associated with PV. A fine-mapping analysis of PV risk in the major histocompatibility complex region showed three independent variants predisposed to PV using stepwise analysis: HLA-DRB1*14:04 (P = 2.47 × 10-38, odds ratio = 6.28), rs7454108 at the TAP2 gene (P = 2.78 × 10-12, odds ratio = 3.25), and rs1051336 at the HLA-DRA gene (P = 3.06 × 10-6, odds ratio = 0.33). A systematic evaluation using gene- and pathway-based analyses showed a high tendency for PV susceptibility genes to be associated with autoimmunity. Our study highlights the involvement of immune-mediated processes in the pathophysiology of PV and illustrates the value of imputation to identify variants in the major histocompatibility complex region.

Author Correction: Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis.

This corrects the article DOI: 10.1038/ncomms7793.

Exome-wide association study identifies four novel loci for systemic lupus erythematosus in Han Chinese population.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of considerable genetic predisposition. Genome-wide association studies have identified tens of common variants for SLE. However, the majority of them reside in non-coding sequences. The contributions of coding variants have not yet been systematically evaluated. METHODS: We performed a large-scale exome-wide study in 5004 SLE cases and 8179 healthy controls in a Han Chinese population using a custom exome array, and then genotyped 32 variants with suggestive evidence in an independent cohort of 13 246 samples. We further explored the regulatory effect of one novel non-coding single nucleotide polymorphism (SNP) in ex vivo experiments. RESULTS: We discovered four novel SLE gene regions (LCT, TPCN2, AHNAK2 and TNFRSF13B) encompassing three novel missense variants (XP_016859577.1:p.Asn1639Ser, XP_016859577.1:p.Val219Phe and XP_005267356.1:p.Thr4664Ala) and two non-coding variants (rs10750836 and rs4792801) with genome-wide significance (pmeta <5.00×10-8). These variants are enriched in several chromatin states of primary B cells. The novel intergenic variant rs10750836 exhibited an expression quantitative trait locus effect on the TPCN2 gene in immune cells. Clones containing this novel SNP exhibited gene promoter activity for TPCN2 (P=1.38×10-3) whose expression level was reduced significantly in patients with SLE (P<2.53×10-2) and was suggested to be further modulated by rs10750836 in CD19+ B cells (P=7.57×10-5) in ex vivo experiments. CONCLUSIONS: This study identified three novel coding variants and four new susceptibility gene regions for SLE. The results provide insights into the biological mechanism of SLE.