Autoantibodies: Potential clinical applications in early detection of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma

Esophageal squamous cell carcinoma(ESCC)and esophagogastric junction adenocarcinoma(EGJA)are the two main types of gastrointestinal cancers that pose a huge threat to human health.ESCC remains one of the most common malignant diseases around the world.In contrast to the decreasing prevalence of ESCC,the incidence of EGJA is rising rapidly.Early detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these cancers.Current approaches for early diagnosis mainly depend on invasive and costly endoscopy.Non-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of patients.Tumor-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis,making them promising biomarkers for early detection and monitoring of ESCC and EGJA.In this review,we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.

Autoantibodies against MMP-7 as a novel diagnostic biomarker in esophageal squamous cell carcinoma

AIM： To evaluate the diagnostic values of serum autoan tibodies against matrix metalloproteinase-7 （MMP-7） in patients with esophageal squamous cell carcinoma （ESCC）. METHODS： The MMP-7 cDNA was cloned from ESCC tissues, and MMP-7 was expressed and purified from a prokaryotic system. MMP-7 autoanUbodies were then measured in sera from 50 patients with primary ESCC and 58 risk-matched controls, using a reverse capture enzyme-linked immunosorbent assay （ELISA） in which autoantibodies to MMP-7 bound to the purified MMP-7 proteins. In addition, MMP-7 autoantibody levels in sera from 38 gastric cancer patients and from control serum samples were also tested. RESULTS： The optimum conditions for recombinant MMP-7 protein expression were determined as 0.04 mmol/L Isopropyl-13-D-Thiogalactopyranoside （IPTG）induction at 37℃ for four hours. The levels of serum autoantibodies against MMP-7 were significantly higher in patients with ESCC than in the matched-control samples （OD450 = 1.69 ±0.08 vs OD450 = 1.55 ± 0.10, P 〈 0.001）. The area under the receiver operating character- istic （ROC） curve was 0.87. The sensitivity and specificity for detection of ESCC were 78.0% and 81.0%, respectively, when the OD450 value was greater than 1.65. Although the levels of autoantibodies against MMP-7 were also significantly higher in patients with gastric cancer compared to control samples （OD450 = 1.62± 0.06 vs OD450 = 1.55±0.10, P 〈 0.001）, the diagnostic accuracy was less significant than in ESCC patients. The area of ROC curve was 0.75, whereas the sensitivity and specificity were 60.5% and 71.7%, respectively, when the cut-off value of OD450 was set at 1.60. CONCLUSION： Serum autoantibody levels of MMP-7 may be a good diagnostic biomarker for esophageal squamous cell carcinoma,

Prevalence of Anti-endothelial Cell Antibodies in Patients with Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases

Objective To investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations. Methods AECAs in sera of 39 CTD patients with PAH,22 CTD patients without PAH,and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated. Results The prevalence of AECAs was 82.1% in CTD patients with PAH,72.7% in CTD patients without PAH,and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%,P<0.05). In CTD patients with PAH,anti-75 kD AECA was more frequently detected in those with Raynaud’s phenomenon or with positive anti-RNP antibody. Conclusion AECAs could be frequently detected in CTD patients with or without PAH,while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.

Presence of disease specific autoantibodies against liver sinusoidal cells in primary biliary cirrhosis

AIM: To investigate the presence of autoantibodies directed against liver sinusoidal cells in primary biliary cirrhosis(PBC).METHODS: Liver biopsies from 21 PBC patients were studied and compared with 12 liver biopsies from disease controls [3 patients with hepatitis B(HBV) virus,3 patients with hepatitis C virus(HCV), 3 patients with non-alcoholic steatohepatitis and 3 patients with acute alcoholic hepatitis(AAH)]. As healthy controls, we used tissue specimens adjacent to metastatic liver adenocarcinoma. Normal serum was taken from staff members of the unit. The determination of the cell type targetedby autoantibodies present in the patients sera was performed by indirect immunofluorescence(IIF) analysis using paraffin-embedded liver sections as a substrate.Sera from homologous or heterologous PBC patients or sera from the disease control group were used as primary antibodies. The presence of autoantibodies was identified using confocal microscopy.RESULTS: In total, 18/21(85.7%) PBC patients exhibited positive staining in the sinusoidal cells, 10/21(47.6%) in lymphocytes, 8/21(38%) in cholangiocytes and 7/21(33.3%) in hepatocytes, when homologous serum and fluorescein isothiocyanate-conjugated immunoglobulin type G(IgG) secondary antibody were used. PBC sections incubated with heterologous PBC serum showed reduced staining(20% for sinusoidal cells, 20% for lymphocytes, 20% for cholangiocytes and 13.3% for hepatocytes). When IgM immunoglobulin, instead of IgG, was used as secondary antibody,positive staining was observed in 75% of lymphocytes,62.5% of cholangiocytes, 37.5% of hepatocytes and50% of the sinusoidal cells with a much stronger staining intensity. No staining was observed when either normal or PBC sera were used as a primary antibody on liver sections from the disease control group. When PBC sera were incubated with healthy control sections,weak positive staining of cholangiocytes was observed in 3/21(14.3%) PBC serum samples. Steatohepatitis serum on PBC sections gave a positive staining of some hepatocytes and lymphocytes but no staining on viral hepatitis sections. Incubation with HBV sera stained some hepatocytes, cholangiocytes and intra-sinusoidal or portal lymphocytes of PBC, HBV and AAH patients but not HCV patients.CONCLUSION: In this study, for the first time in diseased liver tissue, we have demonstrated that a large proportion of PBC patients have disease specific autoantibodies against liver sinusoidal cells.

Recent advancement on autoantigens, autoantibodies and inflammatory cells in subepidermal autoimmune bullous diseases

Subepidermal autoimmune bullous diseases （SABD） are some autoimmune skin diseases that can present in a variety of forms and can be a challenging disease to treat. An overview of the different forms of SABD are discussed including bullous pemphigoid （BP）, epidermolysis bullosa acquisita （EBA）, cicatricial pemphigoid （CP）, bullous systemic lupus erythematosus （BSLE）, and Anti-p200 pemphigoid. Emphasis on recent advancement is presented. In recent years, improved knowledge of the mechanisms of intercellular and cell-matrix adhesion has led to better understanding of the blistering process in some SABD. Defects of such structures cause the subepidermal bullous diseases and have also led to the discovery of new diseases （e.g. anti-p200-pemphigoid）. Recent studies have outlined the important role of autoantibodies, mast cell lymphocytes and their cytokines in pathogenesis of SABD.

Influence of anti-keratin autoantibodies on telomerase activity of squa-mous cell carcinoma

Objective: To investigate the influence of anti-keratin autoantibodies (AK auto Abs) on telom-erase activity of squamous cell carcinoma cultured in vitro and the mechanisms of the inhibitory effects of AK auto Abs on squamous cell carcinoma. Methods: Influence of AK auto Abs on the proliferation of Tca cells was observed by MTT colorimetry. Telomerase activity of cultured Tca cells and human keratinocytes was determined by telomeric repeat amplication protocol-ELISA (TRAP-ELISA) and polyacrylamide gel elec-trophoresis (PAGE). After being treated with AK auto Abs for 36 h at a concentration of 4, 8, 16 mg/L respectively, the changes of telomerase activity of Tea cells were also detected by TRAP-ELISA and PAGE. Results: MTT colorimetric determination showed that the capacity of proliferation of Tca cells correlated negatively with the concentration of AK auto Abs (r= -0. 74, P<0. 01). TRAP-ELISA and PAGE showed that telomerase activity of Tca cells increased significantly compared to that of cultured human keratinocytes (t = 3. 5396, P<0. 01). AK auto Abs at a concentrations of 4, 8, 16 mg/L had significant dose-dependent inhibitory effects on telomerase activity of Tca cells (r= - 0. 8358, P<0. 01). Conclusion: AK auto Abs have a significant dose-dependent inhibitory effect on the proliferation of cultured Tea cells. AK auto Abs inhibit telomerase activity of cultured Tca cells with dose-dependent pattern. It suggests that decrease of telomerase activity may play an important role in the inhibitory effects of AK auto Abs on squamous cell carcinoma.

Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells

Gastric cancer(GC), with its high incidence and mortality rates, is a highly fatal cancer that is common in East Asia particularly in China. Its recurrence and metastasis are the main causes of its poor prognosis. Circulating tumor cells(CTCs) or other blood biomarkers that are released into the circulating blood stream by tumors are thought to play a crucial role in the recurrence and metastasis of gastric cancer. Therefore, the detection of CTCs and other blood biomarkers has an important clinical significance; in fact, they can help predict the prognosis, assess the staging, monitor the therapeutic effects and determine the drug susceptibility. Recent research has identified many blood biomarkers in GC, such as various serum proteins, autoantibodies against tumor associated antigens, and cell-free DNAs. The analysis of CTCs and circulating cell-free tumor DNA(ctDNA) in the peripheral blood of patients with gastric cancer is called as liquid biopsy. These blood biomarkers provide the disease status for individuals and have clinical meaning. In this review, we focus on the recent scientific advances regarding CTCs and other blood biomarkers, and discuss their origins and clinical meaning.

Blood-based biomarkers for early detection of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is a common malignant tumor of the digestive system worldwide,especially in China.Due to the lack of effective early detection methods,ESCC patients often present at an advanced stage at the time of diagnosis,which seriously affects the prognosis of patients.At present,early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy.Therefore,there is an unmet need for a noninvasive method to detect ESCC in the early stages.With the emergence of a large class of non-invasive diagnostic tools,serum tumor markers have attracted much attention because of their potential for detection of early tumors.Therefore,the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC.This article reviews the recent advances in the discovery of blood-based ESCC biomarkers,and discusses the origins,clinical applications,and technical challenges of clinical validation of various types of biomarkers.

Studies of the Kinetochore Proteins of the Regenerating Liver and the Liver Cells of Rats at Different Stages of Development

The kinetochore composition of rat liver cells was studied by indirect immunofluorescence andimmunoblotting using human anti-kinetochore/centromere autoantibodies(ACAs).Besides threemajor antigens(50kD,42 kD and 34 kD),ACAs used in this study could also identify those of 32-30 kD and 20 kD in newborn rat liver cells,90 kD in old rat liver cells,37 kD and 32-30 kD inregenerating liver cells.These results indicate that some kinetochore antigen(s)may be related to cellproliferation or specific for different stages of development.

Increased expression of regulatory T cell-associated markers in recent-onset diabetic children

CD4+CD25hi T cells are thought to be crucial for the maintenance of immunological tolerance to self antigens. In this study, we investigated the frequencies of these cells in the early stage of type 1 diabetes, as well as in a setting of possible pre-diabetic autoimmunity. Hence, the expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi T cells was analyzed using flow cytometry in 14 patients with recent onset type 1 diabetes, in 9 at-risk individuals, and 9 healthy individuals with no known risk for type 1 diabetes. Our results show there were no differences in the frequency of CD4+CD25hi cells between groups. However, compared to controls, recent-onset type 1 diabetic patients had higher expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi cells from peripheral blood. The median fluorescence intensity of FOXP3 was significantly higher in CD4+CD25hi cells from patients with type 1 diabetes than from controls. Furthermore, a positive correlation between the frequency of FOXP3+ cells and the median fluorescence intensity of FOXP3 was observed among patients with type 1 diabetes. These data suggest that the frequency of CD4+CD25hi FOXP3+ T cells in the periphery is not decreased but rather increased at onset of type 1 diabetes. Thus, functional deficiencies rather than reduced numbers of CD4+CD25hi cells could contribute to the development of type 1 diabetes.

血清MMP1和P53自身抗体联合检测对食管鳞状细胞癌的诊断价值

目的:探讨食管鳞状细胞癌(ESCC)患者血清基质金属蛋白酶1(MMP1)和P53自身抗体表达水平及其联合检测的诊断意义。方法:收集2013年3—9月在汕头大学医学院附属肿瘤医院住院治疗的93例ESCC患者,并以同期90例体检者为正常对照组。应用酶联免疫吸附实验(ELISA)检测两组对象血清MMP1和P53自身抗体的表达水平,采用受试者工作特征(ROC)曲线评价诊断效能。结果:血清MMP1含量和P53自身抗体滴度在ESCC组分别为(8.076±5.912)ng/mL和0.291±0.492,正常对照组分别为(4.652±3.346)ng/mL和0.055±0.037,ESCC组均较正常对照组显著升高(均为P<0.01)。ROC曲线分析显示,MMP1诊断ESCC的曲线下面积(AUC)为0.700(95%CI为0.624~0.776),当取最佳诊断截断值7.248 ng/mL时,特异度为83.3%,敏感度为52.7%。P53自身抗体诊断ESCC的AUC为0.713(95%CI为0.638~0.788),诊断截断值为0.080,特异度为83.3%,敏感度为49.5%。两者联合检测诊断ESCC的AUC为0.787(95%CI为0.720~0.854),特异度为83.3%,敏感度为66.7%,优于单独使用MMP1或P53自身抗体。在早期ESCC中,MMP1和P53自身抗体联合检测亦能获得较好的诊断效能,AUC为0.760,95%CI为0.663~0.857,特异度为83.3%,敏感度为66.7%。结论:ESCC患者血清MMP1和P53自身抗体水平均升高,二者联合检测有助于ESCC的早期诊断,可作为ESCC的诊断标志物。

血清NY-ESO-1自身抗体和MMP1联合检测对食管鳞状细胞癌的诊断价值

目的:探讨血清基质金属蛋白酶-1(matrix metalloproteinase-1,MMP1)和纽约食管鳞状细胞癌抗原-1(New York esophageal squamous cell carcinoma 1,NY-ESO-1)自身抗体联合检测在食管鳞状细胞癌中的诊断意义。方法:应用酶联免疫吸附实验检测120例食管鳞状细胞癌患者和120例正常对照血清中MMP1和NY-ESO-1自身抗体的表达水平,采用受试者工作特征(receiver operating characteristic,ROC)曲线评价诊断效能。结果:血清MMP1和NY-ESO-1自身抗体在食管鳞状细胞癌患者中的表达均明显高于正常对照[(8.070±5.738)ng/mL vs(4.331±3.137)ng/mL,Z=6.214,P<0.001;0.463±0.571 vs 0.156±0.086,Z=5.210,P<0.001]。ROC曲线显示,当血清MMP1为最佳诊断临界值10.586 ng/mL时,其在诊断食管鳞状细胞癌的曲线下面积(area under the ROC curve,AUC)为0.732(95%CI:0.671~0.787),敏感度为24.2%,特异度为95.0%。NY-ESO-1自身抗体诊断食管鳞状细胞癌AUC为0.695(95%CI:0.632~0.752),敏感度为33.0%,特异度为95.0%。MMP1和NY-ESO-1自身抗体联合检测诊断食管鳞状细胞癌的AUC为0.800(95%CI:0.744~0.849),敏感度为47.5%,特异度为95.0%。结论:血清MMP1和NY-ESO-1自身抗体联合检测可能有助于提高食管鳞状细胞癌的诊断效能。

靶向淋巴细胞治疗系统性红斑狼疮的研究进展

系统性红斑狼疮(SLE)是一种在组织和器官中表现出高度异质性的自身免疫性疾病,其发病原因目前尚不明确。淋巴细胞是参与SLE发生发展的重要免疫细胞。已有研究认为T细胞、B细胞的异常激活是SLE发病的重要原因之一。本文通过总结T细胞、B细胞在SLE发病机制中的作用,以及靶向T细胞、B细胞治疗SLE相关研究的新进展,为研究SLE的发病机制以及开发治疗SLE的新型药物提供重要的科学依据。

血清中7种肺癌自身抗体对非小细胞肺癌的诊断及预后不良的应用价值

目的探讨血清中7种肺癌自身抗体检测在非小细胞肺癌(NSCLC)临床诊断及预后不良中的应用价值。方法采用回顾性病例对照研究方法收集2017年1月至2018年10月该院收治的173例肺结节患者的临床资料,将其中经临床检查及病理学检查确诊的80例NSCLC患者作为恶性组,将确诊的93例良性肺结节患者作为良性组,另回顾性选取同期在该院进行健康体检的69例健康者作为对照组。所有研究对象均于确诊前或体检时检测血清中7种肺癌自身抗体[肿瘤蛋白P53(P53)、神经元胞质蛋白基因产物9.5(PGP9.5)、干细胞转录因子(SOX2)、G抗原7(GAGE7)、肿瘤抗原4-5(GBU4-5)、黑色素瘤抗原A1(MAGEA1)、肿瘤相关基因(CAGE)]。比较恶性组、良性组和对照组血清P53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGEA1、CAGE水平及其阳性检出率,并绘制基于血清中7种肺癌自身抗体诊断NSCLC及评估预后不良的受试者工作特征(ROC)曲线,观察灵敏度、特异度及曲线下面积(AUC)。另随访1年,根据预后情况将恶性组又分为预后良好组和预后不良组。分析血清中7种肺癌自身抗体水平与NSCLC患者预后的关系。结果恶性组血清P53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGEA1、CAGE水平及其阳性检出率均高于良性组和对照组,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,血清P53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGEA1、CAGE单独及联合检测诊断NSCLC的灵敏度分别为30.00%、23.75%、28.75%、33.75%、25.00%、42.50%、26.25%、68.75%,特异度分别为98.15%、96.91%、93.83%、98.15%、98.15%、87.04%、97.53%、79.01%,AUC分别为0.563、0.498、0.456、0.429、0.407、0.392、0.374、0.705。预后不良组血清P53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGEA1、CAGE水平及其阳性检出率均高于预后良好组,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,血清P53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGEA1、CAGE单独及联合检测预测NSCLC患者预后不良的灵敏度分别为70.83%、75.00%、70.83%、75.00%、66.67%、70.83%、79.17%、91.67%,特异度分别为75.00%、71.43%、73.21%、69.64%、76.79%、75.00%、71.43%、82.14%,AUC分别为0.694、0.672、0.631、0.647、0.636、0.629、0.718、0.862。结论血清中7种肺癌自身抗体单独检测对NSCLC的诊断及预后不良预测均有一定参考价值,但7项联合检测临床价值更高。

2型糖尿病患者胰岛细胞自身抗体、抗谷氨酸脱羧酶抗体水平与糖尿病微血管并发症的关系

目的探讨抗胰岛细胞抗体(ICA)、抗胰岛素抗体(IAA)及抗谷氨酸脱羧酶抗体(GADA)与2型糖尿病(T2DM)患者发生糖尿病微血管并发症(DMAP)的关系。方法对2023年11月-2024年3月本院收治的114例T2DM患者临床资料进行回顾性分析,根据是否发生DMAP将患者分别分入单纯T2DM组(n=61)和并发症组(n=53)。检测所有患者入院时IAA、ICA及GADA水平。采用受试者工作特征(ROC)曲线分析IAA、ICA及GADA对DMAP的评估价值,采用多因素logistic回归分析探讨DMAP的影响因素。结果并发症组患者的ICA、IAA、GADA水平均高于单纯T2DM组,差异均有统计学意义(P<0.05)。ICA、IAA及GADA评估T2DM患者发生DMAP的曲线下面积(AUC)分别为0.792、0.736、0.805,联合检测的AUC为0.912。并发症组患者T2DM病程≥8年比例、有饮酒史比例均高于单纯T2DM组患者,差异均有统计学意义(P<0.05)。logistic回归结果显示:T2DM病程≥8年(OR=2.314,95%CI:1.136~4.714)、ICA≥4183.62 RU/mL(OR=4.221,95%CI:1.849~9.633)、IAA≥5587.37 RU/mL(OR=3.449,95%CI:1.654~7.192)、GADA≥3667.92 IU/mL(OR=5.150,95%CI:2.058~12.888)是T2DM患者发生DMAP的危险因素(P<0.05)。结论ICA、IAA及GADA与T2DM患者发生DMAP密切相关,联合检测有助于DMAP的评估。

非小细胞肺癌术后自身抗体水平及临床意义

目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者手术前后肿瘤相关7项自身抗体(tumor-associated autoantibody,TAAB),包括肿瘤蛋白53(tumor protein 53,p53)、蛋白基因产物9.5(protein gene product9.5,PGP9.5)、性别决定基因家族2(SRY-box containing gene 2,SOX2)、G抗原7(G antigen 7 ATP-dependent RNA helicase,GAGE7)、ATP结合RNA解螺旋酶(ATP-dependent RNA helicase,GBU4-5)、人黑色素瘤抗原A1(melanoma antigen A1,MAGEA1)、肿瘤/睾丸抗原(cancer/testisantigen,CAGE)表达水平动态变化的临床意义。方法选取2019年1月至2022年8月在宁波市医疗中心李惠利医院胸外科接受手术治疗的NSCLC患者41例,采用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测患者血清7项TAAB表达水平。结果鳞癌组PGP9.5手术前后表达水平均明显高于腺癌组(P<0.05),腺癌组GAGE7手术前后表达水平均明显高于鳞癌组(P<0.05)。鳞癌组术后1周GBU4-5表达水平明显高于腺癌组(Z=-2.095,P=0.036)。腺癌组内,术后1周GBU4-5(P=0.027)、CAGE(P=0.042)表达水平较术前明显下降。术后6个月PGP9.5(P=0.004)、GAGE7(P<0.001)、GBU4-5(P=0.014)表达水平较术前明显下降。鳞癌组中,术后1周表达水平差异均无统计学意义(P>0.05)。术后6个月SOX2(P=0.011)表达水平较术前明显下降。与术前比较,术后1周GBU4-5表达水平明显下降(P=0.009)。术后6个月PGP9.5(P=0.003)、GAGE7(P=0.001)、GBU4-5(P=0.013)表达水平明显下降。结论手术干预可降低NSCLC患者7项TAAB表达水平,手术治疗前后监测7项TAAB有助于NSCLC患者手术疗效的评估和术后病情进展的预测。

Autoantibodies against G-Protein-Coupled Receptors Modulate Heart Mast Cells

Mast cells are believed to be involved in myocardial tissue remodelling under pathophysiological conditions. We examined the effects of autoantibodies against G-protein-coupled receptors in sera of patients with heart diseases on myocardial mast cells in the cultured neonatal Sprague-Dawley rat heart cells. Cells collected at day 3 and 10 of the culture were preincubated with autoantibodies against α-adrenoceptor and angiotensin Ⅱ ATl-receptor, agonist phenylephrine and angiotensin Ⅱ, and control IgG. The pretreated cultured cells were stained for selected mast cell markers tryptase, chymase and TNF-α The cultured cells were also processed for observation with electron microscopy. The autoantibodies-treatment of the 3-day cultured cells caused both increased intensity of immunofluorescence （p 〈 0.05） and their enlarged diameters of the mast cells when compared to age-matched ones. In contrast, the fluorescence of preincubated 10-day-old mast cells was decreased compared with controls （p 〈 0.01）. In control samples, the fluorescence of 10-day-old mast cells was significantly higher than that of 3-day-old ones （p 〈 0.001）. Results of electron microscopy examination demonstrated there was an increased granulation of treated 3-day-old mast cells, while a degranulation of mast cells at day 10 of application. The results suggest the modulation effect of the autoantibodies against G-protein-coupled receptors on mast cells, indicating a potential functional link between the autoantibodies against G-protein-coupled receptors and the mast cells in progression of heart disease.

肺癌7项抗体水平与NSCLC患者化疗效果及预后的关系

目的研究肺癌7项抗体水平与非小细胞肺癌(NSCLC)患者化疗效果及预后转归的关系。方法选取太和县人民医院从2022年6月至2023年12月收治的42例NSCLC患者开展研究。所有受试者均进行4个周期的化学治疗(化疗)。将其按照化疗疗效的差异分作有效组(n=25)与无效组(n=17)。对比两组肺癌7项抗体水平,并以受试者工作特征(ROC)曲线分析肺癌7项抗体评估NSCLC患者化疗疗效的效能。此外,将受试者按照预后转归的差异分作预后良好组(n=21)及预后不良组(n=21)。对比两组肺癌7项抗体水平,并以多因素Logistic回归分析明确肺癌7项抗体水平与NSCLC患者预后转归的关系。结果化疗有效组肺癌7项抗体水平均低于无效组(P<0.05)。经ROC曲线分析证实,肺癌7项抗体(CAGE、GAGE7、GBU4-5、P53、PGP95、SOX2、MAGEA1)评估NSCLC患者化疗疗效的效能均较佳,曲线下面积分别为0.861、0.769、0.778、0.786、0.793、0.842、0.833。预后不良组肺癌7项抗体水平均高于预后良好组(P<0.05)。经多因素Logistic回归分析证实,肺癌7项抗体为NSCLC患者预后不良的危险因素水平(OR>1,P<0.05)。结论肺癌7项抗体水平与NSCLC患者化疗效果及预后密切相关,随着肺癌7项抗体水平的升高,NSCLC患者化疗效果及预后越差。

肿瘤患者外周血免疫指标的临床价值与展望

肿瘤局部的免疫反应和炎症反应所形成的免疫微环境在肿瘤发生、发展和转移中发挥关键作用。肿瘤免疫微环境由肿瘤细胞、免疫细胞(中性粒细胞、巨噬细胞和淋巴细胞)及其产生的细胞因子、趋化因子等构成,彼此相互作用,形成复杂的网络,影响机体免疫状态。外周血免疫指标检测可为肿瘤患者的辅助诊断、预后判断和疗效预测提供有价值的参考依据,尤其是在免疫治疗评估中具有良好的临床应用潜力。肿瘤患者个体免疫状态差异大,因此检测结果的解释具有挑战性。文章针对肿瘤患者外周血免疫指标的临床价值和应用前景进行评论。

系统性红斑狼疮患者血清sMICA,sMICB水平与自身抗体表达及疾病活动度的相关性研究

目的探讨循环可溶性MHC-I类链相关蛋白A[soluble major histocompatibility complex class I-related chain A,sMICA)、可溶性MHC-I类链相关蛋白B(soluble major histocompatibility complex class I-related chain B,sMICB]与系统性红斑狼疮(systemic lupus erythematosus,SLE)疾病活动性、自身抗体的关系。方法选择2020年1月~2023年1月重庆大学附属黔江医院收治的156例SLE患者(SLE组)和门诊体检中心体检的103例健康志愿者(对照组)。根据SLE疾病活动度评分(SLE disease activity index,SLEDAI)将SLE患者分为轻度活动组(n=43)、中度活动组(n=69)和重度活动组(n=44)。检测血清sMICA,sMICB水平以及自身抗体、外周血NK细胞占比,Spearman或Pearson分析sMICA,sMICB与评分、自身抗体、外周血NK细胞占比的相关性,受试者工作特征(ROC)曲线用来分析sMICA和sMICB诊断SLE活动度的价值。结果SLE组血清sMICA(173.65±23.92 pg/ml),sMICB(96.35±15.74 pg/ml)水平高于对照组(32.51±6.27 pg/ml,12.03±2.47 pg/ml),外周血CD3^(-)CD56^(+)NK细胞(12.02%±2.65%)占比低于对照组(18.35%±3.71%),差异具有统计学意义(t=58.498,53.897,-16.010,均P<0.05)。重度活动组血清sMICA,sMICB水平高于中度活动组和轻度活动组(t=8.192,12.352;19.652,23.742,均P<0.05),外周血CD3^(-)CD56^(+)NK细胞占比低于中度活动组和轻度活动组(t=8.154,10.658,均P<0.05),差异具有统计学意义。不同疾病活动SLE患者抗‐dsDNA抗体、抗核抗体、抗核小体抗体和抗组蛋白抗体阳性率比较,差异具有统计学意义(χ^(2)=8.795,7.216,7.539,8.946,均P<0.05)。SLE患者血清sMICA,sMICB水平与SLEDAI评分、抗‐dsDNA抗体、抗核抗体、抗核小体抗体、抗组蛋白抗体呈正相关(r=0.206~0.402,均P<0.05),与外周血CD3^(-)CD56^(+)NK细胞占比呈负相关(r=-0.563,-0.427,均P<0.05)。sMICA和sMICB诊断SLE重度活动的曲线下面积为0.652,0.704,联合sMICA,sMICB诊断SLE重度活动的曲线下面积为0.812,高于单独诊断(Z=3.050,2.346,均P<0.05)。结论SLE患者血清sMICA和sMICB水平增高,且与SLE自身抗体阳性率增加、外周血NK细胞占比降低、疾病活动性增强有关,可作为SLE的潜在标志物。