STAT3-Dependent Effects of Polymeric Immunoglobulin Receptor in Regulating Interleukin-17 Signaling and Preventing Autoimmune Hepatitis

One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

Potential role of killer immunoglobulin receptor genes among individuals vaccinated against hepatitis B virus in Lebanon

AIM To explore the role of killer immunoglobulin receptor(KIR) genes in responsiveness or non-responsiveness to vaccination against hepatitis B virus.METHODS We recruited 101 voluntary participants between March 2010 and December 2011. Sera samples from vaccinated and non-vaccinated participants were tested for the presence of anti-HBs antibodies as a measure of protection against hepatitis B, hepatitis B surface antigen and hepatitis B core antibody as indicators ofinfection by enzyme-linked immunosorbent assay. KIR gene frequencies were determined by polymerase chain reaction.RESULTS Sera samples from 99 participants were tested for the levels of anti-HBs as an indicator of protection(≥ 10 mI U/ml) following vaccination as defined by the World Health Organization international reference standard. Among the vaccinated participants, 47%(35/74) had anti-HBs titers above 100 mI U/ml, 22%(16/74) had antiHBs ranging between 10-100 mI U/ml, and 20%(15/74) had values of less than 10 mI U/ml. We report the lack of significant association between the number of vaccine dosages and the titer of antibodies among our vaccinated participants. The inhibitory KIR2Dl1, KIR2Dl4, KIR3Dl1, KIR3Dl2, and KIR3 Dl were detected in more than 95%, whereas KIR2Dl2, KIR2Dl3, KIR2Dl5(KR2Dl5A and KIR2Dl5B) were expressed in 56%, 84% and 42%(25% and 29%) of participants, respectively. The observed frequency of the activating KIR genes ranged between 35% and 55% except for KIR2DS4, detected in 95% of the study participants(40.6% 2DS4*001/002; 82.2% 2DS4*003/007). KIR2DP1 pseudogene was detected in 99% of our participants, whereas KIR3DP*001/02/04 and KIR3DP1*003 had frequencies of 17% and 100%, respectively. No association between the frequency of KIR genes and anti-HBs antibodies was detected. When we compared the frequency of KIR genes between vaccinated individuals with protective antibodies titers and those who lost their protective antibody levels, we did not detect a significant difference. KIR2Dl5 B was significantly different among different groups of vaccinated participants(group Ⅰ > 100 mI U/ml, group Ⅱ 10-100 mI U/ml, group Ⅲ < 10 mI U/ml and group Ⅳ with undetectable levels of protective antibodies). CONCLUSION To our knowledge, this is the first study screening for the possible role of KIR genes among individuals vaccinated against hepatitis B virus(HBV). Our results can be used to design larger studies to better understand the role of KIR genes in protection against or susceptibility to HBV post vaccination.

Axon regeneration impediment: the role of paired immunoglobulin-like receptor B

Regenerative capacity is weak after central nervous system injury because of the absence of an enhancing microenvironment and presence of an inhibitory microenvironment for neuronal and axonal repair. In addition to the Nogo receptor（Ng R）, the paired immunoglobulin-like receptor B（Pir B） is a recently discovered coreceptor of Nogo, myelin-associated glycoprotein, and myelin oligodendrocyte glycoprotein. Concurrent blocking of Ng R and Pir B almost completely eliminates the inhibitory effect of myelin-associated inhibitory molecules on axonal regeneration. Pir B participates in a key pathological process of the nervous system, specifically axonal regeneration inhibition. Pir B is an inhibitory receptor similar to Ng R, but their effects are not identical. This study summarizes the structure, distribution, relationship with common nervous system diseases, and known mechanisms of Pir B, and concludes that Pir B is also distributed in cells of the immune and hematopoietic systems. Further investigations are needed to determine if immunomodulation and blood cell migration involve inhibition of axonal regeneration.

Effects of immunoglobulin D on expression of IgD receptor and protein tyrosine kinase signaling in human CD4^+ T cells

OBJECTIVE To observe whether human CD4^+T cells could be activated by immuno-globulin D(IgD) via IgD receptor(IgDR)-Lck.METHODS Human CD4^+T cells were purified from peripheral blood mononuclear cells(PBMCs) with microbeads.The viability of T cells were detected by CCK-8.The binding affinity and expression of IgDR on T cells were detected by flow cytometry.The protein expression of IgDR,Lck and P-Lck were analyzed by western blot.RESULTS IgD could concentration-dependent bind to IgDR on CD4^+T cells.The expression of IgDR was increased in response to treatment with IgD in a time-dependent and concentration-dependent manner.Stimulating by IgD resulted in enhanced phosphorylation of Lck compared with that in the medium control sample.The expression of Lck was not changed.As inhibitor of PTK,Herbimycin A or A770041,which combined with IgD could significantly inhibit phosphorylation of Lck(Tyr^(394)).The proliferation promoting effect of IgD was blocked by Herbimycin A or A770041.IgD could stimulate CD4^+T cell activation and proliferation through upregulating activating tyrosine residue of Lck(Tyr^(394)) phosphorylation.CONCLUSION These results demonstrate that IgD exaggerates CD4^+T cell activities,which may be through promoting Lck phosphorylation.

Distribution of paired immunoglobulin-like receptor B in the nervous system related to regeneration difficulties after unilateral lumbar spinal cord injury

Paired immunoglobulin-like receptor B（Pir B） is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regeneration. The regulatory effect of Pir B on injured nerves has received a lot of attention. To better understand nerve regeneration inability after spinal cord injury, this study aimed to investigate the distribution of Pir B（via immunofluorescence） in the central nervous system and peripheral nervous system 10 days after injury. Immunoreactivity for Pir B increased in the dorsal root ganglia, sciatic nerves, and spinal cord segments. In the dorsal root ganglia and sciatic nerves, Pir B was mainly distributed along neuronal and axonal membranes. Pir B was found to exhibit a diffuse, intricate distribution in the dorsal and ventral regions. Immunoreactivity for Pir B was enhanced in some cortical neurons located in the bilateral precentral gyri. Overall, the findings suggest a pattern of Pir B immunoreactivity in the nervous system after unilateral spinal transection injury, and also indicate that Pir B may suppress repair after injury.

Clonal immunoglobulin heavy chain and T-cell receptor γ gene rearrangements in primary gastric lymphoma

AIM:To study the diagnostic value of immunoglobulin heavy chain(IgH)and T-cell receptorγ (TCR-γ)gene monoclonal rearrangements in primary gastric lymphoma(PGL).METHODS:A total of 48 patients with suspected PGL at our hospital were prospectively enrolled in this study from January 2009 to December 2011.The patients were divided into three groups(a PGL group,a gastric linitis plastica group,and a benign gastric ulcer group)based on the pathological results(gastric mucosal specimens obtained by endoscopy or surgery)and follow-up.Endoscopic ultrasonography(EUS)and EUSguided biopsy were performed in all the patients.The tissue specimens were used for histopathological examination and for IgH and TCR-γ gene rearrangement polymerase chain reaction analyses.RESULTS:EUS and EUS-guided biopsy were successfully performed in all 48 patients.In the PGL group(n=21),monoclonal IgH gene rearrangements were detected in 14(66.7%)patients.A positive result for each set of primers was found in 12(57.1%),8(38.1%),and 4(19.0%)cases using FR1/JH,FR2/JH,and FR3/JH primers,respectively.Overall,12(75%)patients with mucosal-associated lymphoid tissue lymphoma(n=16)and 2(40%)patients with diffuse large B-cell lymphoma(n=5)were positive for monoclonal IgH gene rearrangements.No patients in the gastric linitis plastica group(n=17)and only one(10%)patient in the benign gastric ulcer group(n=10)were positive for a monoclonal IgH gene rearrangement.No TCRgene monoclonal rearrangements were detected.The sensitivity of monoclonal IgH gene rearrangements was 66.7%for a PGL diagnosis,and the specificity was96.4%.In the PGL group,8(100%)patients with stage IIE PGL(n=8)and 6(46.1%)patients with stage IE PGL(n=13)were positive for monoclonal IgH gene rearrangements.CONCLUSION:IgH gene rearrangements may be associated with PGL staging and may be useful for the diagnosis of PGL and for differentiating between PGL and gastric linitis plastica.

免疫抑制受体LILRB4在肿瘤和炎症性疾病中的研究进展

白细胞免疫球蛋白样受体LILRB4(ILT3或CD85k)是免疫抑制受体家族成员,主要表达于髓系来源免疫细胞的细胞膜,在免疫调节中通过激活自身抑制基序(ITIM)或抑制Fc受体激活基序(ITAM)发挥免疫抑制作用。在肿瘤中,LILRB4受体被激活后产生免疫抑制性的肿瘤微环境协助肿瘤的侵袭和转移。在炎症疾病中,LILRB4在单核细胞、巨噬细胞、肥大细胞等多种细胞上表达并减轻炎症反应。目前LILRB4已成为肿瘤以及多种炎症性疾病的治疗靶点,针对急性髓细胞性白血病(AML)的抗LILRB4单克隆抗体已进入临床试验。本综述从LILRB4的结构分布、信号转导、治疗靶点、新药开发等几方面进行探讨。

共抑制受体T细胞免疫球蛋白和免疫受体酪氨酸抑制基序结构域免疫抑制机制的研究进展

恶性肿瘤的发生、发展与免疫检查点受体有紧密联系,肿瘤细胞可以通过激活免疫检查点来逃避免疫监视。T细胞免疫球蛋白和免疫受体酪氨酸抑制基序结构域(TIGIT)是一种在免疫细胞上表达的抑制性受体。TIGIT可以通过多种机制抑制T细胞和天然杀伤(NK)细胞等免疫细胞的功能,使肿瘤细胞逃避免疫系统的监视,本文将对TIGIT的免疫抑制机制研究进展进行系统综述。

应用Q-PCR定性检测KIR基因有无方法的建立

目的建立定性检测KIR基因有无的Q-PCR方法。方法根据高分辨水平中国人群KIR等位基因的多态性,并参考国际IPD-KIR数据库,针对16种KIR基因及2DS4-Normal、2DS4-Deleted两种亚型,设计KIR基因特异性引物用于Q-PCR扩增反应;同时设置一孔阴性对照、一孔阳性对照(特异性扩增人体生长激素HGH基因片段),以监控假阳性、假阴性的结果。为验证Q-PCR方法的可靠性,随机选择302份已采用KIR PCR-SSP商品化试剂盒检测的标本,采用Q-PCR方法盲检和对比。结果300人份的Q-PCR检测结果与已知的PCR-SSP检测结果相符,有2份标本结果不一致,其中1例标本的2DS5基因Q-PCR检测结果为阴性,而PCR-SSP检测结果为阳性;另一例标本2DS1基因Q-PCR检测结果为阳性,而PCR-SSP检测结果为阴性。对2份标本分别进行2DS5、2DS1基因测序分型,证实Q-PCR定性检测结果正确。结论本文建立的KIR Q-PCR方法结果准确、可靠,可用于KIR基因有无的定性检测。

补体受体免疫球蛋白超家族分子在调节肝脏免疫反应中的研究进展

库普弗细胞(KC)是肝脏免疫细胞的重要组成部分,其对于维持组织稳态和应对肝损伤的快速反应至关重要。补体受体免疫球蛋白超家族分子(CRIg)是KC膜上的一种受体蛋白,其既能以补体结合的方式捕获流经肝脏血液中的病原体,也可以通过调节肝脏内的免疫细胞介导肝脏免疫反应。近年来CRIg的研究进一步证实了其在调节肝脏免疫中的关键地位,本文综述了CRIg的主要作用方式以及其在调节肝脏免疫中的新进展。

LAIR-1通过阻断JAK2 V617F突变的人HEL细胞JAK/STAT和PI3K/AKT/mTOR信号通路抑制其增殖并促进其凋亡

目的研究人白细胞相关免疫球蛋白样受体1(LAIR-1)对Janus激酶2(JAK2)V617F突变的人急性髓系白血病HEL细胞JAK/信号转导子与转录激活子(STAT)和磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/AKT/mTOR)信号通路的调节作用,以及对细胞增殖和凋亡的影响。方法采用反转录PCR和基因测序鉴定JAK2 V617F突变;应用免疫共沉淀和Western blot法鉴定LAIR-1募集的蛋白酪氨酸磷酸酶(PTP)种类;采用CCK-8法检测HEL细胞的增殖;采用异硫氰酸荧光素标记的膜联素Ⅴ/碘化丙啶(annexinⅤ-FITC/PI)双标记结合流式细胞术检测HEL细胞的凋亡率;采用Western blot法检测JAK/STAT和PI3K/AKT/mTOR通路蛋白酪氨酸磷酸化水平及细胞周期蛋白D1(cyclin D1)、Bcl2相关X蛋白(BAX)和B细胞淋巴瘤因子2(Bcl2)的蛋白表达。结果在JAK2 V617F突变的HEL细胞中,LAIR-1与其配体胶原蛋白结合后可募集含Src同源域2磷酸酶2(SHP-2);LAIR-1可以下调HEL细胞JAK2、STAT1、STAT3、STAT5、AKT和mTOR的蛋白酪氨酸磷酸化水平,并能够显著抑制cyclin D1和Bcl2的表达,而对BAX的表达水平未见显著影响;LAIR-1能够明显抑制HEL细胞的增殖,促进HEL细胞凋亡。结论在JAK2 V617F突变的人白血病HEL细胞中,LAIR-1可通过募集SHP-2抑制JAK/STAT和PI3K/AKT/mTOR信号通路的活化,进而抑制HEL细胞的增殖,促进细胞凋亡。

穿山龙总皂苷对膜性肾病大鼠肾组织M型PLA2R和IgG4表达的影响及其机制

目的 分析穿山龙总皂苷对膜性肾病大鼠肾组织M型磷脂酶A2受体(Phospholipase A2 receptor, PLA2R)和免疫球蛋白G亚型4(Immunoglobulin G4,IgG4)表达影响及可能机制。方法 将40只SPF级雄性SD大鼠按随机数字表法分为对照组、模型组、贝那普利组(10 mg/kg)、低和高剂量穿山龙总皂苷组(80 mg/kg、160 mg/kg),每组各8只。除对照组,其余4组采用Border法制备膜性肾病模型,造模成功后,贝那普利组灌胃给予贝那普利10 mg/(kg·d),低和高剂量穿山龙总皂苷组分别灌胃给予穿山龙总皂苷80 mg/(kg·d)、160 mg/(kg·d),对照组、模型组灌胃给予10 ml/(kg·d)生理盐水。连续给药4周后,检测24 h尿蛋白、白蛋白、血肌酐、血尿素氮、尿酸水平,HE染色观察肾脏病理改变,蛋白免疫印迹法检测肾脏中M型PLA2R、IgG4、磷酸化磷脂酰肌醇3-激酶(Phosphorylated phosphoinositide 3-kinase, p-PI3K)、磷酸化蛋白激酶B(Phosphorylated protein kinase B,p-AKT)、核因子E2相关因子2(Nuclear factor E2-related factor 2,Nrf2)、血红素加氧酶(Heme oxygenase-1,HO-1)表达水平。结果 与模型组比较,贝那普利组、高剂量穿山龙总皂苷组白蛋白水平明显升高,血肌酐、血尿素氮、尿酸水平明显降低,差异均有统计学意义(P>0.05)。与模型组比较,贝那普利组、低剂量和高剂量穿山龙总皂苷组肾脏病理改变明显改善,24 h尿蛋白水平及肾脏中M型PLA2R、IgG4、p-PI3K、p-AKT表达水平明显降低,肾脏中Nrf2、HO-1表达水平明显增加,差异均有统计学意义(P<0.05)。结论 穿山龙总皂苷对膜性肾病大鼠的肾脏具有保护作用,其机制可能与降低PLA2R、IgG4表达,抑制PI3K/AKT通路,激活Nrf2/HO-1通路相关。

IgA血管炎发病机制及治疗的研究进展

IgA血管炎(IgAV)是儿童常见的全身性小血管炎疾病,它有IgA1免疫复合物沉着、中性粒细胞和补体因子浸润的特征,其发病机制仍不明。IgAV常累及皮肤小血管、消化道、关节及肾脏。症状有一定自限性,但小部分患者会进展成类似IgA肾病的肾炎,出现血尿、蛋白尿,继而发展为终末期肾病。含有半乳糖缺乏IgA1(Gd-IgA1)的免疫复合物在IgAV的病理生理过程中起着关键作用;通过Fc受体(CD89),诱导血管周围的中性粒细胞炎症和肾小球系膜增生和炎症。本文就IgA、IgA受体、中性粒细胞以及补体系统、遗传和感染等因素在IgAV发病机制中的作用及新疗法的发现作一综述。

新生儿Fc受体及其抑制剂在原发免疫性血小板减少症中的研究进展

原发免疫性血小板减少症(ITP)是一种由血小板自身抗体介导的自身免疫性疾病,大多数ITP患者具有免疫球蛋白G(IgG)亚型的抗血小板抗体,其通过与血小板和巨核细胞上糖蛋白的相互作用导致血小板破坏增加和抑制血小板的生成。新生儿Fc受体(FcRn)用于维持人体内IgG水平稳态。通过FcRn抑制剂靶向FcRn可以降低血液中的致病性IgG,证明了其对治疗ITP和其他自身免疫性疾病有效,并在一定程度上可改善ITP患者的血小板计数。efgartigimod、Rozanolixizumab均可与FcRn结合进而导致循环IgG减少。FcRn抑制剂还能间接延长罗米司亭的半衰期以提高治疗效果。本综述简要总结了ITP中血小板的破坏和生成抑制机制、FcRn和FcRn抑制剂作用的分子机制、FcRn抑制剂在ITP中的应用以及FcRn与罗米司亭、静脉注射Ig的联系。

遗传调控下免疫相关血浆蛋白对帕金森病的效应

目的 探讨免疫相关血浆蛋白与帕金森病(Parkinson's disease, PD)的联系。方法 通过对4907种免疫相关血浆蛋白的全基因组关联研究数据进行分析,评估血浆蛋白对PD风险的直接影响。研究还利用单细胞核RNA测序数据进行蛋白表达分析。结果 4种免疫相关蛋白质脑源性多巴胺营养因子(cerebral dopamine neurotrophic factor, CDNF)、组织蛋白酶B(cathepsin B,CTSB)、免疫球蛋白G Fc受体2a(FCGR2A)、血红蛋白β亚基(HBB)与PD风险存在潜在联系;其中,CDNF、CTSB、HBB表达增高有助于降低PD风险(OR=0.871,95%CI:0.779~0.973,P=0.015;OR=0.835,95%CI:0.758~0.920,P=0.001;OR=0.735,95%CI:0.631~0.857,P=0.001),而FCGR2A表达增高与PD风险增高相关(OR=1.137,95%CI:1.058~1.223,P=0.001)。单细胞测序分析蛋白表达及其在脑中不同细胞类型中分布,CDNF、CTSB在大脑的多种细胞中大量表达;FCGR2A主要在大脑小胶质细胞中表达;HBB在大脑中几乎不表达。结论 研究揭示了CDNF、CTSB、FCGR2A及HBB 4种蛋白质与PD风险的潜在关联,强调了PD遗传风险变异通过调节这些免疫相关蛋白表达来影响PD发生。此外,单细胞表达数据揭示相关免疫蛋白在大脑的表达模式。

Primary anaplastic lymphoma kinase-positive large B-cell lymphoma of the left bulbar conjunctiva: A case report

BACKGROUND Anaplastic lymphoma kinase(ALK)-positive large B-cell lymphoma(LBCL)is an aggressive and rare variant of diffuse LBCL.Herein,we report an uncommon case of stage IE extranodal ALK-positive LBCL initially originating in the bulbar con-junctiva.CASE SUMMARY A 63-year-old woman presented with a mass in the left bulbar conjunctiva that had persisted for six months,accompanied by swelling and pain that had per-sisted for 3 d.Eye examination revealed an 8 mm slightly elevated pink mass in the lower conjunctival sac of the left eye.Microscopically,the tumor was com-posed of large immunoblastic and plasmablastic large lymphoid cells with scattered anaplastic or multinucleated large cells.Immunophenotypically,the neoplastic cells were positive for ALK,CD10,CD138,Kappa,MUM1,BOB.1,OCT-2,CD4,CD45,EMA,CD79a,CD38,and AE1/AE3,and negative for CD20,PAX5,Lambda,BCL6,CD30 and all other T-cell antigens.The results of gene rearrangement tests showed monoclonal IGH/IGK/IGL and TCRD rearran-gements.Fluorescence in situ hybridization studies did not reveal any BCL2,BCL6 or MYC rearrangements.Furthermore,Epstein-Barr virus was not detected by in situ hybridization in the lesions.Based on the histopathological and imaging examinations,the neoplasm was classified as stage IE ALK-positive LBCL.No further treatments were administered.At the 6,15,and 21 mo postoperative follow-up visits,the patient was in good condition,without obvious discomfort.This case represents the first example of primary extranodal ALK-positive LBCL presenting as a bulbar conjunctival mass,which is extremely rare and shares morphological and immunohistochemical features with a variety of other neo-plasms that can result in misdiagnosis.CONCLUSION Awareness of the condition presented in this case report is necessary for early and accurate diagnosis and appropriate treatment.

血清SIGIRR、sTRAIL与传染性单核细胞增多症患儿外周血T细胞亚群和肝脏损伤的关系研究

目的 探讨传染性单核细胞增多症(infectious mononucleosis, IM)患儿血清单免疫球蛋白白细胞介素1相关受体(single immunoglobulin interleukin-1 related receptor, SIGIRR)、可溶性肿瘤坏死因子相关的凋亡诱导配体(soluble tumor necrosis factor-related apoptosis-inducing ligand, sTRAIL)与外周血T细胞亚群和肝脏损伤的关系。方法 选取2020-01/2023-01月作者医院收治的95例IM患儿为IM组,另选取同期100例体检健康儿童为对照组。根据IM患儿是否发生肝脏损伤分为肝脏损伤组(n=49)和无肝脏损伤组(n=46)。采用酶联免疫吸附试验法检测血清SIGIRR、sTRAIL水平,流式细胞术检测外周血T细胞亚群(CD3^(+)、CD16^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))。通过多因素Logistic回归分析探讨IM患儿肝脏损伤的影响因素,受试者工作特征(receiver operating characteristic, ROC)曲线分析血清SIGIRR、sTRAIL对IM患儿肝脏损伤的预测价值。结果 与对照组健康儿童比较,IM组患儿血清SIGIRR水平和外周血CD16^(+)、CD4^(+)、CD4^(+)/CD8^(+)降低,血清sTRAIL水平和外周血CD3^(+)、CD8^(+)升高(P均<0.05)。Pearson相关性分析显示,IM患儿血清SIGIRR水平与外周血CD16^(+)、CD4^(+)、CD4^(+)/CD8^(+)呈正相关关系,与CD3^(+)、CD8^(+)呈负相关关系(P<0.05),血清sTRAIL水平与外周血CD16^(+)、CD4^(+)、CD4^(+)/CD8^(+)呈负相关关系,与CD3^(+)、CD8^(+)呈正相关关系(P<0.05)。单因素分析结果显示,病程、白细胞计数、CD3^(+)、CD16^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)、SIGIRR水平、sTRAIL水平为IM患儿肝脏损伤的影响因素(P均<0.05)。多因素Logistic回归分析结果显示,CD3^(+)、CD16^(+)、sTRAIL升高为IM患儿肝脏损伤的独立危险因素,CD4^(+)/CD8^(+)、SIGIRR升高为其保护因素(P<0.05)。ROC曲线分析结果显示,血清SIGIRR、sTRAIL单独和二者联合预测IM患儿肝脏损伤的曲线下面积(area under the curve, AUC)分别为0.786、0.737、0.836,二者联合对IM患儿肝脏损伤预测效能的AUC大于SIGIRR、sTRAIL单独的预测效能。结论 IM患儿血清SIGIRR水平降低和sTRAIL水平升高与外周血T细胞亚群异常、肝脏损伤密切相关,血清SIGIRR、sTRAIL水平联合检测对IM患儿肝脏损伤的预测价值更高。

TACI融合蛋白对免疫球蛋白A肾病大鼠肾脏损害的影响

目的探讨TACI融合蛋白(TACI-Ig)对免疫球蛋白A肾病(IgAN)大鼠肾脏损害的影响。方法将24只SD大鼠随机分为对照组、模型组、TACI-Ig组、药物对照组,每组6只。正常对照组、模型组给予生理盐水,TACI-Ig组给予TACI-Ig(14.36 mg/kg),药物对照组给予醋酸泼尼松(5 mg/kg)。比较各组24 h尿蛋白定量(24h-UP)、血清肌酐(Scr)、尿素氮(BUN)、低半乳糖基化IgA1(Gd-IgA1)、Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核转录因子κB(NF-κB)蛋白及mRNA水平,并分析TACI-Ig对肾脏损害的影响。结果模型组24h-UP水平显著高于正常对照组,而TACI-Ig组、药物对照组24h-UP水平显著低于模型组,差异有统计学意义(P<0.05)。TACI-Ig组血清Scr水平低于模型组,差异有统计学意义(P<0.05)。TACI-Ig组、药物对照组肾组织系膜区沉积免疫复合体的增加受到明显抑制。模型组大鼠血清Gd-IgA1水平高于正常对照组,而低于TACI-Ig组,差异有统计学意义(P<0.01)。药物对照组血清Gd-IgA1水平低于模型组,而高于TACI-Ig组,差异有统计学意义(P<0.01)。TACI-Ig组TLR4、MyD88、NF-κB蛋白水平低于模型组,差异有统计学意义(P<0.05)。药物对照组TLR4、MyD88蛋白水平高于TACI-Ig组,差异有统计学意义(P<0.05)。TACI-Ig组TLR4、MyD88、NF-κB mRNA水平低于模型组,差异有统计学意义(P<0.05)。结论TACI-Ig对IgAN有较好的治疗作用,可改善IgAN大鼠肾功能,抑制肾小球系膜基质扩张和系膜细胞增殖。

阿美替尼、吉非替尼治疗EGFR突变局部晚期非小细胞肺癌的效果及预后

目的探讨阿美替尼、吉非替尼治疗表皮生长因子受体(EGFR)突变局部晚期非小细胞肺癌(NSCLC)的效果及预后。方法选取2019年3月至2022年9月确诊的100例EGFR突变局部晚期NSCLC,根据治疗方式不同分为A组(n=57)和B组(n=43),A组采用阿美替尼治疗,B组采用吉非替尼治疗,均持续治疗2个周期。比较2组的客观缓解率(ORR)和疾病控制率(DCR)、治疗前后血清EGFR水平和免疫球蛋白指标[免疫球蛋白M(IgM)、免疫球蛋白A(IgA)、免疫球蛋白G(IgG)]、毒副反应发生率,所有患者随访12~42个月,绘制生存曲线,比较2组中位总生存期(OS)和中位无进展生存期(PFS)。结果A组ORR和DCR分别为28.07%和77.19%,B组分别为11.63%和44.19%,差异均有统计学意义(P<0.05)。治疗后,A组血清EGFR水平较B组低,IgM、IgA和IgG水平较B组高,差异有统计学意义(P<0.05)。A组<3级毒副反应发生率为71.93%,≥3级毒副反应发生率为21.05%,B组<3级毒副反应发生率为48.84%,≥3级毒副反应发生率为41.86%,差异有统计学意义(P<0.05)。A组中位OS和中位PFS分别为16.9个月和5.8个月,B组中位OS和中位PFS分别为10.5个月和4.0个月,差异有统计学意义(P<0.05)。结论与吉非替尼比较,阿美替尼治疗EGFR突变局部晚期NSCLC患者效果更好,可以更好控制病情发展,改善EGFR水平和免疫指标,提高患者生存率,且具有一定的安全性。

黄芪甲苷Ⅳ通过抑制TIM-1信号通路增加Th1/Th2细胞比率减轻IgA肾病小鼠肾损伤

目的探讨黄芪甲苷Ⅳ(AS-Ⅳ)对IgA肾病(IgAN)小鼠1型辅助T(Th1)细胞/Th2细胞平衡的影响及其可能作用机制。方法建立BALB/c小鼠IgAN模型,造模成功小鼠随机分为模型组、AS-Ⅳ低、中和高剂量组各10只,另设对照组10只。AS-Ⅳ低、中和高剂量组小鼠灌胃(12.5、25、50)mg/kg AS-Ⅳ混悬液(生理盐水配制),对照组及模型组给予等量生理盐水。测定各组小鼠24 h尿蛋白(24 hUPr)含量和尿红细胞计数;测定小鼠血尿素氮(BUN)、血清肌酐(Scr)和白蛋白(ALB)水平;ELISA检测各组小鼠血清γ干扰素(IFN-γ)、白细胞介素4(IL-4)和IL-10水平;流式细胞术检测小鼠外周血Th1/Th2细胞比率;HE染色观察小鼠肾组织病理学变化;反转录PCR和Western blot法分别检测小鼠肾组织中T细胞免疫球蛋白和黏蛋白结构域1(TIM-1)、Toll样受体4(TLR4)的mRNA和蛋白表达。结果与模型组比较,AS-Ⅳ低、中和高剂量组小鼠第12周和第15周尿红细胞计数、24 h UPr、BUN、Scr、IL-4、IL-10水平、Th2细胞比例、TIM-1与TLR4 mRNA和蛋白表达水平均明显降低,ALB、IFN-γ水平、Th1细胞比例和Th1/Th2细胞比率升高,且以AS-Ⅳ高剂量组效果最佳。结论AS-Ⅳ通过抑制TIM-1信号通路,增加Th1/Th2细胞比率,抑制炎症反应,减轻IgAN小鼠肾损伤。