Immune checkpoint-targeted immunotherapy has achieved unprecedented success, yet its limitations remain evident. Human leukocyte antigen-G (HLA-G), a novel immune checkpoint, exhibits restricted physiologic expression but is broadly expressed in various tumors, conferring systemic immune suppressive functions via different types of immune inhibitory receptors, and is associated with a poor prognosis for patients with cancer, making it an attractive tumor-site-agnostic candidate target for cancer immunotherapy. Since 2020, clinical trials employing different strategies of HLA-G-targeted immunotherapy for various advanced solid cancers have been conducted. Herein, the molecular characteristics of HLA-G, HLA-G-receptor binding interactions, and HLA-G-targeted preclinical investigations and clinical trials for solid cancer immunotherapy are highlighted, and the challenges associated with translating these findings into clinical settings are also discussed.

IntroductionThe concept that human leukocyte antigen-G (HLA-G) expression is specifically in various malignant lesions but absent in adjacent normal tissues has been well documented, and HLA-G is acknowledged as a novel immune checkpoint.MethodsIn this study, HLA-G expression in 523 gastric cancer (GC) lesions and 283 case-matched peritumoral tissues (PTTs) was analyzed by immunohistochemistry. The clinical significance of HLA-G expression in GC lesions and case-matched PTTs was evaluated, and a specific HLA-G-positive subpopulation in PTTs was identified.ResultsData showed that HLA-G expression was significantly different between GC lesions (370/523, 70.7%) and PTTs (238/283, 84.1%; p<0.001). HLA-G in GC lesions was more frequently observed in older patients (76.2% vs. 65.3%, p=0.006), and HLA-G in PTTs was more commonly observed in female patients (92.0% vs. 80.5%, p=0.014). Survival analysis revealed that HLA-G expression in PTTs (overall survival: 42.0 months vs. 56.7 months, p=0.023), but not in GC lesions (52.1 months vs. 50.9 months, p=0.623), is significantly associated with poor prognosis. The fundic gland mucous neck cells were the only subpopulation that expressed HLA-G.DiscussionOur findings, for the first time, suggest that fundic gland mucous neck cell HLA-G expression in PTTs is associated with GC progression.

Background:Human leukocyte antigen (HLA)-G has multiple isoforms with unique molecular structures and receptor-binding specificities. Different HLA-G isoform(s) may have distinct clinical relevance. Because of the lack of isoform-specific monoclonal antibodies (mAbs), the clinical significance of HLA-G isoforms (HLA-G1 to HLA-G7), except HLA-G1 and HLA-G5, remains largely unknown. Methods:In this study, mAbs against HLA-G2/6 and HLA-G1/4/5 isoforms were generated and characterized. Expression of HLA-G2/6 and HLA-G1/4/5 isoforms was analyzed by immunohistochemistry, and clinical significance was evaluated retrospectively in 345 patients with colorectal cancer (CRC). Results:The expression rate of HLA-G2/6 (90/345, 26.1%) was significantly lower than that of HLA-G1/4/5 (275/345, 79.7%; p < 0.001). Patients with HLA-G2/6 expression had significantly poorer overall survival (OS) (median OS: 6.3 years [95% CI: 4.1-8.5] vs. 10.0 years [95% CI: 7.6-12.4]; p = 0.008). Multivariate Cox proportional-hazard model results indicated that HLA-G2/6 was an independent prognostic factor for CRC (hazard ratio [HR] = 1.530, 95% CI: 1.125-2.081; p = 0.007). Moreover, HLA-G2/6 expression showed stratified prognostic significance among several CRC patient subgroups, specifically in female patients (p = 0.003), younger patients (<66 years p < 0.001), patients with colon cancer (p = 0.045), those at stage pT3 (p = 0.008), pN1 (p = 0.020), pM0 (p = 0.009), and AJCC stage III (p = 0.005). However, no statistical significance was found between HLA-G1/4/5 isoform expression and patient prognosis in CRC. Conclusions:This is the first study to generate mAbs for the HLA-G2/6 and HLA-G1/4/5 isoforms. Our findings reveal that HLA-G2/6-but not HLA-G1/4/5-expression is an independent prognostic indicator for patients with CRC. In the context of precision medicine, our study also suggests that HLA-G isoform typing may be necessary for HLA-G-targeted cancer immunotherapy.

The prognostic significance of metastasis-associated in colon cancer-1 (MACC1) has been explored in a variety of malignancies. However, its clinical relevance in patients with gastric cancer (GC) is limited, also remains controversial. In this study, we retrospectively evaluated the prognostic value of lesion MACC1 expression in 347 GC patients. Lesion MACC1 expression was analyzed with immunohistochemistry and grouped as MACC1low (n = 172) and MACC1high (n = 175) cases. Data revealed that the degree of MACC1 expression is not related to patient sex, age and disease stage (all p > 0.05). Survival analysis showed that only post-operation advanced pT (p = 0.018), pN (p < 0.001), pM (p = 0.001) and AJCC stages (p < 0.001) are significantly associated with shorter survival, while no obvious difference was observed between MACC1low and MACC1high cases (p = 0.158). However, we found that survival for female (p = 0.032), older (p = 0.028), and early disease stage (pT stage I + II, p = 0.033) patients with MACC1high are remarkably worse than those with MACC1low. In summary, our findings revealed that, though MACC1 expression is not associated with the survival of the whole cohort, the prognostic risk stratification value of lesion MACC1 expression in subgroups of patients with gastric cancer should be noted.

Although detailed underlying mechanisms for the pathogenesis of autoimmune diseases remain largely unknown, multiple factors such genetic and epigenetic background, environmental inducers, and dysregulation of immune tolerance for self-antigens have been considered to be associated with a variety of autoimmune diseases. Human leukocyte antigen (HLA) system, the most polymorphic complex in human genome, functions fundamental roles in immune homeostasis by interaction with both immune activating and inhibitory receptors expressed on different types of immune cells. In line with this, an increasing evidence of genetic predisposition and molecular functions of the non-classical HLA class I antigen HLA-G has been revealed in the clinical significance of autoimmune diseases. Tissue HLA-G expression was firstly observed on the extravillous cytotrophoblasts, and later its immune suppressive features have become well documented. In contrast to its high polymorphic classical HLA class I (HLA-A, HLA-B, and HLA-C) counterparts, HLA-G is with very limited genetic variations, while at least four membrane-bound (HLA-G1–HLA-G4) and three soluble (HLA-G5–HLA-G7) isoforms have been identified, which differs either in extracellular domains or in intracellular cytoplasmic tails generated by HLA-G primary transcript alternative splicing. Functionally, HLA-G can induce profound immune inhibition by interacting with a panel of HLA-G-binding immune receptors such as immunoglobulin-like transcripts (ILT)-2, ILT-4, and killer inhibitory receptor (KIR) 2DL4 differentially expressed on autoimmune diseases related T cells, natural killer cells (NK), B cells, dendritic cells (DCs), or macrophages. In this context, induction of HLA-G expression could have a protective effect to diminish auto-reactive immune responses among autoimmunity. In this chapter, we focus on the genetic association, molecular function, and mechanisms of HLA-G-mediated immune tolerance in autoimmune diseases.

ObjectiveTo evaluate the prognostic significance of peripheral lymphocyte count and its derived inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), in a cohort of patients with gastric cancer (GC).MethodsIn this retrospective study, the clinical characteristics and follow-up information, both pre- and post-operative within one week of laboratory findings, of 338 patients with GC who underwent radical gastrectomy were retrieved, and their prognostic significance was evaluated.ResultsBoth lower pre- and post-operative lymphocyte counts and higher NLR and SSI were significantly related to advanced tumour (pT) and disease stages (American Joint Committee on Cancer [AJCC]) in patients with GC. Log-rank survival analysis showed that, in addition to traditional pT, pN, pM, and AJCC stages, both lower pre- (p = 0.041) and post-operative (p = 0.002) lymphocyte counts and higher NLR (ppre < 0.001 and ppost = 0.008) and SSI (ppre = 0.014 and ppost = 0.145) were associated with worse survival. Cox proportional hazards analysis revealed that pre-operative NLR (p = 0.018; hazard ratio = 1.778) was an independent predictor of prognosis in patients with GC. Moreover, when the pre-operative NLR was divided into NLRlow and NLRhigh, NLRhigh showed stratified prognostic value for patient sex (male, p = 0.001; female, p = 0.044), age (younger, p = 0.005; older, p = 0.005), and AJCC stage III (p = 0.007).ConclusionPre-operative NLR is an independent prognostic factor for patients with GC and has stratified prognostic value for patients with AJCC stage III GC.

ObjectiveHuman leukocyte antigen-G (HLA-G) and its receptors, including immunoglobulin-like transcripts (ILT)-2 and ILT-4, are closely associated with cancer development and clinical outcomes of patients. However, the clinical significance of HLA-G and ILT-2/-4 in gastric cancer (GC) is limited.MethodsIn this study, the percentage of HLA-G-, ILT-2 and ILT-4 positive tumor cells in 127 GC lesion suspensions of tumor cells gated for epithelialcelladhesionmolecule(EpCAM) was determined using multicolor flow cytometry and their clinical significance was evaluated.ResultsOur data showed that the median percentages of HLA-G-, ILT-2, and ILT-4 expressing GC cells were 18.0%, 67.80%, and 1.42%, respectively, and co-expression of HLA-G/ILT-2, HLA-G/ILT-4, and ILT-2/ILT-4 was 16.9%, 1.42%, and 1.70%, respectively. Kaplan-Meier survival results revealed that besides post-operation N status (p = 0.006), M status (p = 0.001), and AJCC clinical stage (p < 0.001), only high percentage of ILT-4+ GC cells was a significant factor for worse survival of patients with GC (overall survival [OS]: 42.9 months vs. 84.5 months; p = 0.031). However, among female patients with GC (n = 31), high percentage of either HLA-G+ (OS: 18.5 months vs. 89.3 months; p = 0.001) or ILT-4+ (OS: 17.9 months vs. 85.8 months; p = 0.002) GC cells was markedly associated with a poor prognosis.ConclusionOur findings revealed that among HLA-G, ILT-2, and ILT-4, only a high percentage of ILT-4+ GC cells was significantly related to poor prognosis in the entire cohort of patients with GC. However, high percentage of HLA-G+ and ILT-4+ GC cells is associated with poor clinical outcome among female patients with GC.

Immune checkpoint inhibitors (ICIs) have become a promising area of research for cancer treatment. In addition to the well-known ICIs targeting PD-1/PD-L1, HLA-G/ILT-2/-4 is relatively new immune checkpoint that has been evaluated in early clinical trials in patients with advanced solid tumors. In this study, the expression of HLA-G (n=157), ILT-2/4 (n=82), and PD-L1 (n=70) in epithelial cell adhesion molecule (EpCAM)-positive colorectal cancer (CRC) cells was analyzed by multicolor flow cytometry, and the prognostic significance of these molecules was evaluated. In EpCAM+ CRC cells, the median percentages of HLA-G, ILT-2, ILT-4, and PD-L1 were 14.90%, 67.70%, 8.55% and 80.30%, respectively. In addition, a positive correlation was observed between them (all p<0.001). Higher levels of these immune checkpoint proteins are associated with lymph node metastasis. In addition to the AJCC stage (p=0.001), Kaplan-Meier survival analysis showed that higher levels of HLA-G (p=0.041), ILT-2 (p=0.060), ILT-4 (p<0.001), PD-L1 (p=0.012), HLA-GILT4 (p<0.001) and ILT-2ILT-4 (p<0.001) were significantly associated with shorter survival of CRC patients. When CRC patients were stratified by early and advanced AJCC stages, HLA-G levels were only related to the survival among CRC patients with early disease stage (p=0.024), while ILT-4 levels were significant for both CRC patients with early (p=0.001) and advanced (p=0.020) disease stages. Multivariate cox regression analysis revealed that advanced AJCC stage (HR=2.435; p=0.005) and higher ILT-4 levels (HR=2.198; p=0.063) were independent risk factors for poor outcomes in patients with CRC. In summary, among the immune checkpoints, HLA-G/ILT-2/4 and PD-L1, ILT-4 is the most significant prognostic indicator of CRC. This finding indicated that a combination of immunotherapy strategies, such as ILT-4 blockade, could improve the clinical outcomes in patients with cancer. Moreover, multicolor flow cytometry can be employed as a reliable and efficient, alternative to immunohistochemistry, for evaluating the immune checkpoint proteins expressed in tumor lesions.

COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has threatened public health worldwide. Host antiviral immune responses are essential for viral clearance and disease control, however, remarkably decreased immune cell numbers and exhaustion of host cellular immune responses are commonly observed in patients with COVID-19. This is of concern as it is closely associated with disease severity and poor outcomes. Human leukocyte antigen-G (HLA-G) is a ligand for multiple immune inhibitory receptors, whose expression can be upregulated by viral infections. HLA-G/receptor signalling, such as engagement with immunoglobulin-like transcript 2 (ILT-2) or ILT-4, not only inhibit T and natural killer (NK) cell immune responses, dendritic cell (DC) maturation, and B cell antibody production. It also induces regulatory cells such as myeloid-derived suppressive cells (MDSCs), or M2 type macrophages. Moreover, HLA-G interaction with CD8 and killer inhibitory receptor (KIR) 2DL4 can provoke T cell apoptosis and NK cell senescence. In this context, HLA-G can induce profound immune suppression, which favours the escape of SARS-CoV-2 from immune attack. Although detailed knowledge on the clinical relevance of HLA-G in SARS-CoV-2 infection is limited, we herein review the immunopathological aspects of HLA-G/receptor signalling in SARS-CoV-2 infection, which could provide a better understanding of COVID-19 disease progression and identify potential immunointerventions to counteract SARS-CoV-2 infection.

Objective: Re-positivity of SARS-CoV-2 in discharged COVID-19 patients have been reported; however, early risk factors for SARS-CoV-2 re-positivity evaluation are limited. Methods: This is a prospective study, a total of 145 COVID-19 patients were treated and all discharged according to the guideline criteria by Mar 11th 2020. After discharge, clinical visits and viral RT-PCR tests by the second and fourth week follow-up were carried-out. Patient demographic and clinical characteristics and laboratory data on admission and discharge were retrieved, and predictive factors for SARS-CoV-2 re-positivity were analyzed. Results: 13 out of 145 (9.0%) COVID-19 patients were confirmed re-positivity of SARS-CoV-2 by RT-PCR test. The median interval between disease onset to recurrence was 38 days. SARS-CoV-2 re-positive cases were of significantly longer virus shedding duration, notably higher body temperature, heart rate and lower TNF-alpha and IgG levels on admission. Covariate logistic regression analysis revealed virus shedding duration and IgG levels are independent risk factors for SARS-CoV-2 return positive after discharge. Conclusion: Longer viral shedding duration and lower IgG levels are risk factors for re-positivity of SARS-CoV-2 for discharged COVID-19 patients.

目的 探讨原因不明复发性流产患者(unexplained recurrent spontaneous abortion,URSA)外周血中CD19+ CD24highCD27+调节性B细胞(regulatory B cells,Bregs)及细胞因子与复发性流产关系.方法 采用流式细胞术(FCM)分析原因不明复发性流产患者组(URSA)、正常孕妇组(NP)、正常非孕组(NNP)外周血中CD19+ CD24high CD27+ Bregs表达比例及酶联免疫双抗体夹心法(ELISA)检测外周血中细胞因子IL-2、IFN-γ、TNF-α、IL-4、IL-6、IL-10、TGF-β水平.结果 外周血CD19+ CD24 high CD27+ Bregs表达比例URSA组明显低于NP组(P＜0.01),与NNP组比较差异无统计学意义(P＞0.05).外周血中细胞因子IL-2、IFN-γ、TNF-α水平URSA组明显高于NP组、NNP组(P＜0.05);外周血中细胞因子IL-4、IL-6、IL-10、TGF-β水平URSA组明显低于NP组(P＜0.01)、NNP组(P＜0.05).相关性分析显示,URSA组外周血CD19+ CD24high CD27+ Bregs细胞比例与IL-10水平呈正相关(r=0.56,P＜0.01),而与TGF-β水平无明显相关性(r =0.24,P＞0.05).结论 外周血中CD19+ CD24high CD27+ Bregs细胞数量及功能异常可能是导致复发性流产免疫功能紊乱的重要原因之一.

Human leukocyte antigen-G (HLA-G) has been widely acknowledged to play critical roles in fetal-maternal maintenance. However, the significance of using maternal serum sHLA-G to detect prenatal chromosomal abnormality has not been investigated. In China, prenatal screening using maternal α-fetoprotein (AFP), unconjugated estriol (uE3), and free β subunit human chorionic gonadotropin (β-hCG) in the second trimester has been widely applied. In this study, we evaluated the use of sHLA-G as a screening marker, compared with traditional second trimester prenatal screening. Serum samples from 1,019 singleton women in their second trimester were assessed. Among them, 139 infants were confirmed with trisomy 21 (T21) by karyotyping, 83 were confirmed with trisomy 18 (T18), and the remaining 797 infants had no abnormalities. The sHLA-G levels in maternal sera were significantly lower in pregnant women with T18 fetuses (median: 47.8 U/ml, range: 9.8–234.2 U/ml) and significantly higher in those with T21 fetuses (median: 125.7 U/ml, range: 28.7–831.7 U/ml), compared with the normal controls (median: 106.3 U/ml, range: 50.5–1136.4 U/ml) ( p < 0.001). The risk values of the screening of T21 or T18 fetuses were assessed using mean and standard deviation log 10 analyte multiples of median (MoM) which showed that the predictive values of sHLA-G were the same as free β-hCG, and superior to AFP and uE3 for T18 screening. Logistic regression analysis revealed that sHLA-G MoM was the highest risk factor associated with pregnant women carrying T18 fetuses [Exp(B): 171.26, 95% CI: 36.30–807.97, p < 0.001]. Receiver operating characteristic (ROC) analysis revealed that the area under ROC curve for sHLA-G MoM was 0.915 (95% CI, 0.871–0.959, p < 0.001), for AFP MoM was 0.796 (95% CI, 0.730–0.861, p < 0.001), for free β-hCG MoM was 0.881 (95% CI, 0.829–0.934, p < 0.001), and for uE3 MoM was 0.876 (95% CI, 0.828–0.923, p < 0.001) in the T18 group. sHLA-G MoM demonstrated the best sensitivity and negative predictive value. For the first time, our findings reveal that sHLA-G is a better second trimester screening marker for the detection of T18 fetuses and the combined application of sHLA-G with AFP, free β-hCG, and uE3 could improve clinical screening for T18 fetuses.

Human leukocyte antigen G (HLA-G) is known as a novel immune checkpoint molecule in cancer; thus, HLA-G and its receptors might be targets for immune checkpoint blockade in cancer immunotherapy. The aim of this study was to systematically identify the roles of checkpoint HLA-G molecules across various types of cancer. ONCOMINE, GEPIA, CCLE, TRRUST, HAP, PrognoScan, Kaplan-Meier Plotter, cBioPortal, LinkedOmics, STRING, GeneMANIA, DAVID, TIMER, and CIBERSORT were utilized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. In this study, we comprehensively analysed the heterogeneous expression of HLA-G molecules in various types of cancer and focused on genetic alterations, coexpression patterns, gene interaction networks, HLA-G interactors, and the relationships between HLA-G and pathological stage, prognosis, and tumor-infiltrating immune cells. We first identified that the mRNA expression levels of HLA-G were significantly upregulated in both most tumor tissues and tumor cell lines on the basis of in-depth analysis of RNAseq data. The expression levels of HLA-G were positively associated with those of the other immune checkpoints PD-1 and CTLA-4. Abnormal expression of HLA-G was significantly correlated with the pathological stage of some but not all tumor types. There was a significant difference between the high and low HLA-G expression groups in terms of overall survival (OS) or disease-free survival (DFS). The results showed that HLA-G highly expressed have positive associations with tumor-infiltrating immune cells in the microenvironment in most types of tumors (P<0.05). Additionally, we identified the key transcription factor (TF) targets in the regulation of HLA-G expression, including HIVEP2, MYCN, CIITA, MYC, and IRF1. Multiple mutations (missense, truncating, etc.) and the methylation status of the HLA-G gene may explain the differential expression of HLA-G across different tumors. Functional enrichment analysis showed that HLA-G was primarily related to T cell activation, T cell regulation, and lymphocyte-mediated immunity. The data may provide novel insights for blockade of the HLA-G/ILT axis, which holds potential for the development of more effective antitumour treatments.

Signaling pathway between human leukocyte antigen (HLA)-G and immune inhibitory receptors immunoglobulin-like transcript (ILT)-2/4 has been acknowledged as one of immune checkpoints, and as a potential target for cancer immunotherapy. Like other immune checkpoints, inter- and even intra-tumor heterogeneity of HLA-G could render a rather complexity for HLA-G-target immunotherapy. However, little information for intra-tumor heterogeneity of HLA-G is available. In this study, HLA-G expression in a serial section of colorectal cancer (CRC) lesions from three CRC patients (each sample with serial section of 50 slides, 10 randomized slides for each antibody), three different locations within a same sample (five CRC), and three case-matched blocks that each includes 36 esophageal cancer samples, were evaluated with immunohistochemistry using anti-HLA-G antibodies (mAbs 4H84, MEM-G/1 and MEM-G/2 probing for all denatured HLA-G isoforms, 5A6G7 and 2A12 probing for denatured HLA-G5 and HLA-G6 isoforms). Our results revealed that, in addition to the frequently observed inter-tumor heterogeneity, intra-tumor heterogeneous expression of HLA-G is common in different areas within a tumor in CRC and esophageal cancer samples included in this study. Moreover, percentage of HLA-G expression probed with different anti-HLA-G antibodies also varies dramatically within a tumor. Given HLA-G has been considered as an important immune checkpoint, intra-tumor heterogeneity of HLA-G expression, and different specificity of anti-HLA-G antibodies being used among studies, interpretation and clinical significance of HLA-G expression in cancers should be with caution.

Background: Abnormal peripheral immunological features are associated with the progression of coronavirus disease 2019 (COVID-19). Methods: Clinical and laboratory data were retrieved in a cohort of 146 laboratory-confirmed COVID-19 patients. Potential risk factors for the development of severe COVID-19 were evaluated. Results: On admission, lymphocytes, CD3+, CD4+ and CD8+ T cells, eosinophils, and albumin and pre-albumin were dramatically lower, whereas neutrophils, and interleukin (IL)-10, C-reactive protein (CRP), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were significantly higher in severe cases. By the second week after discharge, all variables improved to normal levels. Covariate logistic regression results showed that the CD8+ cell count and CRP level were independent risk factors for severe COVID-19. Conclusion: Lower peripheral immune cell subsets in patients with severe disease recovered to normal levels as early as the second week after discharge. CD8+ T cell counts and CRP levels on admission are independent predictive factors for severe COVID-19.

AbstractObjectivesHost immune responses are indispensable to combat the disease. We report the dynamics of peripheral immune cells, cytokines, and human leucocyte antigen‐G (HLA‐G) and its receptor expressions in a patient suffering from critical COVID‐19 pneumonia to convalescence.MethodsClinical data of the patient were collected from medical records. The expressions of HLA‐G and receptors ILT2, ILT4 and KIR2DL4 in peripheral immune cells were measured with flow cytometry.ResultsFrom critical COVID‐19 to the convalescent stage, early lymphopenia was improved (median: 0.6 × 109 L−1 vs. 0.9 × 109 L−1, P = 0.009), and an obvious fluctuation in WBC and neutrophil counts was observed. Initially, low levels of CD4+ T cells (from 120 to 528 μL−1) and CD8+ T cells (from 68 to 362 μL−1) gradually increased to normal levels. Meanwhile, high IL‐6 (from 251.8 to 6.32 pg mL−1), IL‐10 (from 39.53 to 5.21 pg mL−1) and IFN‐γ (from 13.55 to 3.16 pg mL−1) levels decreased, and IL‐4 (from 2.36 to 3.19 pg mL−1) and TNF‐α (from 2.27 to 20.2 pg mL−1) levels increased quickly when the viral RNA returned negative. Moreover, the percentage of HLA‐G+ T cells, B cells and monocytes follows high–low–high pattern, while the percentage of receptors ILT2‐, ILT4‐ and KIR2DL4‐expressing cells remained relatively stable.ConclusionOur findings provide valuable information on the dynamics of early peripheral immunological responses in SARS‐CoV‐2 infection. CD4+ and CD8+ T cells, cytokines and HLA‐G+ immune cells are associated with the natural history of the critical COVID‐19 patient; however, future studies are necessary.

BACKGROUND: Pneumonia coronavirus disease 2019 (COVID-19) has became a pandemic. However, information on early risk factors for the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral positivity is not yet available. METHODS: In this prospective study, a cohort of 137 patients with confirmed SARS-CoV-2 were enrolled. Clinical information and laboratory data were retrieved from electronic medical records. Viral positivity duration was calculated by the interval from the day of confirmed SARS-CoV-2 positive results to the day SARS-CoV-2 testing showed negative results in these 137 patients with COVID-19. Early risk factors for the duration of SARS-CoV-2 viral positivity were evaluated. RESULTS: The median SARS-CoV-2 viral positivity duration is 12 days (range, 4 to ~45) for this cohort. Cox regression results showed a significantly shorter viral positivity duration was related to younger age (hazard ratio [HR], .658; P = .017); disease not being severe (HR, .653; P = .076); higher lymphocyte (HR, 1.464; P = .033), eosinophil (HR, 1.514; P = .020), and CD8+ T-cell (HR, 1.745; P = .033) counts; and lower IL-6 (HR, .664; P = .036) and IL-10 (HR, .631; P = .021). Multivariate analysis with covariable-adjusted results showed that the CD8+ T-cell count (HR, 2.376; P= .114) was a predominant risk factor for the duration of SARS-CoV-2 viral positivity. CONCLUSIONS: Our findings show early laboratory parameters such as CD8+ T-cell count to be risk factors for the duration of SARS-CoV-2 viral positivity, which has significance in the control and prevention of the disease.

目的:分析Turner综合征嵌合体核型患者额外小标记染色体(small supernumerary marker chromosomes，sSMC)的来源与形态。方法:对1例常规G显带分析核型为45，X[26]/46，X，＋mar[43]嵌合体的患者进行荧光原位杂交、高通量全基因组测序、 SRY基因Sanger测序分析，明确其sSMC片段来源和存在形态。 结果:患者G显带核型为45，X[26]/46，X，＋mar[43]。荧光原位杂交结果核型为45，X的细胞37个；核型为46，X，＋mar的细胞63个。sSMC有两种形态：一种整条染色体两端各可见一个清晰红色信号，提示该sSMC来源于有双着丝粒Y染色体且同源；另一种只见到一个红色信号，提示该sSMC来源于有一个着丝粒Y染色体。C显带显示Y染色体异染色质缺失。Y染色体 AZF区微缺失筛查分析 SRY存在。 SRY基因突变检测未发现异常。高通量测序检测染色体基因组微缺失微重复结果，Y染色体q11.221q12位置存在约42.88 Mb缺失。患者核型最终定为45，X[26]/46，X，del(Y)(q11.22q12)[24]/46，X，pus idic(Y)(q11.22)[19]。 结论:本例mos 45，X[26]/46，X，＋mar[43]Turner综合征患者的sSMC同时存在双着丝粒状、带有着丝粒的染色体小片段两种形态。精确定位sSMC来源和形态，可为遗传咨询和产前诊断提供参考。