过敏性紫癜患者血清中IL-27、IL-17的表达及意义

目的 探讨过敏性紫癜(Henoch-Schoenlein purpura,HSP)患者急性期血清中IL-27、IL-17的表达水平。方法 以本院2017年12月至2018年11月收治的56例急性期过敏性紫癜患者为研究对象,同期行健康体检的28例志愿者为对照组,采用酶联免疫吸附法(ELISA)检测入选者外周血IL-27、IL-17的表达情况;采用相关分析法分析IL-27与IL-17表达的相关性以及与患者临床资料指标白细胞(WBC)、血小板(PLT)、C反应蛋白(CRP)、血沉(ESR)、(D-二聚体)D-Dimer、补体(C3、C4)、类风湿因子(RF)、胱抑素C(Cys-C)、免疫球蛋白(IgA、IgG、IgM、IgE)、抗链球菌溶血素O(ASO)的关系。结果 HSP患者急性期血清IL-27的水平较正常对照组降低,IL-17的水平较正常对照组增高,差异均具有统计学意义(P0.05);IL-27与IL-17、抗溶血性链球菌O(ASO)呈负相关(P=0.016;P=0.034),IL-17与免疫球蛋白IgA呈正相关(P=0.002)。结论 过敏性紫癜患者血清中IL-27降低,IL-17升高,且IL-27水平与IL-17呈负相关,说明IL-27可能对IL-17具有免疫调节的作用,可能参与过敏性紫癜的致病过程并在疾病发展过程中发挥保护性作用。     

过敏性紫癜患者血清IL-34水平的变化及意义

目的:探讨过敏性紫癜(Henoch-Schoenlein purpura,HSP)患者急性期血清中IL-34 的表达及意义。方法:选取HSP 患者38 例,同期匹配的健康人21 例作为对照组,采用酶联免疫吸附法(ELISA)及化学发光法检测血清中IL-34、IL-6、TNF-β表达水平;采用相关分析法分析IL-34 与患者临床资料指标的关系以及与IL-6、TNF-β表达的相关性。结果:HSP 患者急性期血清IL-34、IL-6、TNF-β水平均较正常对照组增高,差异具有统计学意义(P<0.001);血清IL-34 和超敏C 反应蛋白(hs-CRP)、IL-6 水平之间呈正相关(分别是r =0.453,P =0.004;r =0.469,P =0.003)。结论:IL-34 可能参与过敏性紫癜的致病过程;可能与过敏性紫癜促炎因子的异常表达有关,促进血管炎症的发生发展。     

过敏性紫癜患儿血管内皮细胞凋亡与血清IgA水平关系探讨

目的:探讨过敏性紫癜(HSP)患儿血管内皮细胞(VEC)凋亡与其血清IgA水平关系.方法:采用皮肤环钻行皮肤组织活检,TUNEL法检测HSP患儿皮肤VEC凋亡,ELISA法检测血清IgA含量,Pearson分析HSP患儿VEC凋亡与IgA表达的关系.另分离HSP患儿血清中IgA,观察其诱导人脐静脉内皮细胞(HUVEC)凋亡的情况.结果:显微镜下凋亡的VEC细胞核呈现棕黄色,HSP患儿普通、肾、腹型VEC凋亡细胞数目与健康对照组比较有统计学意义(P<0.01),且VEC凋亡与IgA高水平表达有关,同时HSP患儿血清中分离的IgA可以诱导培养的HUVEC凋亡.结论:VEC凋亡在HSP血管内皮损伤中起着重要作用,HSP患儿血清IgA可能是导致其VEC凋亡的重要因素.     

血清25-羟维生素D在过敏性紫癜中的研究

目的 探讨血清25-羟维生素D[25-（OH）D] 维生素D水平与HSP发病的关系。方法 选择2017年12月~2018年12月至我院就诊的过敏性紫癜患儿49例设为实验组,另选取40例健康儿童设为健康对照组,采用化学发光法测定两组血清25-羟维生素D水平,免疫浊度法测定补体、免疫球蛋白并进行比较,分析其相关性。结果 实验组血清25-（OH）D水平为（19.061±6.572）ng/ml,低于健康对照组的（30.789±1.880）ng/ml,差异有统计学意义（t=-11.628,P＜0.05）;Pearson相关分析或Spearman秩相关分析示,实验组血清25-羟维生素D水平与免疫球蛋白IgA水平呈负相关（r=-0.352,P＜0.05）,与补体（C3、C4）、免疫球蛋白（IgG、IgM）水平间无明显相关性（r=0.199、0.248、-0.165、-0.204,均P＞0.05）。结论 过敏性紫癜患儿中25羟维生素D可能参与了过敏性紫癜的发病过程。     

儿童过敏性紫癜急性期免疫功能探讨

目的:总结儿童过敏性紫癜(Henoch-Schonlein purpura,HSP)的细胞及体液免疫特征,分析其与紫癜性肾炎(Henoch-Sch(o)nlein purpura nephritis,HSPN)的关系,探讨细胞免疫及体液免疫功能在HSP发病机制中的作用及临床检测价值.方法:HSP急性期患儿190例,按有无肾脏损害分为紫癜性肾炎组(HSPN)和非肾炎组(NHSPN),流式细胞仪免疫荧光法检测T淋巴细胞亚群、自然杀伤细胞(Natural killer cells,NK cells)、B淋巴细胞变化,ELISA法检测血清IL4、IL-10、TNF-α的含量,速率散射比浊法检测外周血免疫球蛋白IgG、IgM、IgA、IgE、C3、C4水平.结果:190例HSP患儿中,合并肾脏损害33例,不合并肾脏损害157例.与对照组相比,急性期HSP组CD19细胞绝对值、IL-4、IL-10、TNF-α、IgG、IgA、IgE、补体C3显著升高(P均＜0.05),CD3、CD4、CD8、NK细胞绝对值显著降低(P均＜0.05);HSP患儿中,HSPN组的IL-10、IgA水平高于NHSPN组(P＜0.05),两组之间其余指标的差异无统计学意义(P均＞0.05).IgA水平升高组HSPN发生率(21.64％)高于IgA水平正常组(7.14％,x2=5.785,P＜0.05).IL-10水平与IgA呈正相关(r=0.425 9,P＜0.05),IL-4水平与IgE呈正相关(r=0.541 7,P＜0.05).结论:HSP急性期存在细胞及体液免疫功能的紊乱,均参与了HSP的发病机制,表现为细胞免疫功能低下,引起炎性介质分泌增多,导致多克隆B细胞活化及免疫球蛋白的分泌增加,介导了系统性微小血管炎,其中IgA介导的体液免疫紊乱在HSP的发病机制中起了主要作用;HSPN的IgA水平升高更为显著,可能是预测HSP发生肾脏损害的一个危险因素.     

特发性血小板减少性紫癜患者血清及树突状细胞分泌APRIL、BAFF研究

目的:通过探讨特发性血小板减少性紫癜(ITP)患者血清及外周血单个核细胞来源树突状细胞(MoDC)分泌的增殖诱导配体(APRIL)、B细胞活化因子(BAFF)特点,进一步明确ITP的发病机制。方法:研究16例初诊(初诊组)、14例治疗后获得有效(显效或良效,有效组)的ITP患者,14例健康对照组。ELISA法检测外周血清及MoDC经LPS活化后的上清APRIL、BAFF,荧光实时定量PCR测定活化后MoDC的BAFF、APRIL表达。结果:血清及DC培养上清APRIL、BAFF水平、MoDC的APRIL、BAFFmRNA表达量初诊组均明显高于对照组及有效组;除MoDC的BAFF mRNA与血小板计数之间,血清APRIL与MoDC的APRIL mRNA表达量之间无相关关系外,其余ITP患者血清、MoDC培养上清APRIL、BAFF、MoDC的APRIL、BAFF mRNA表达量之间分别有正相关关系,而与血小板计数之间均有负相关关系,对照组各参数之间除上清APRIL、BAFF分别与MoDC的APRIL、BAFF mRNA表达量之间有正相关关系外其余均无相关关系(均P0.05)。结论:DC分泌的APRIL、BAFF与ITP发病及病情进展有密切关系,DC可能通过分泌APRIL、BAFF起重要作用。     

过敏性紫癜患儿热休克蛋白70抗体检测的意义

目的探讨热休克蛋白70在过敏性紫癜发病机制中的作用。方法采用蛋白质免疫印迹酶联免疫吸附法（Western blot ELISA）测定37例病例组与35例对照组血浆中热休克蛋白70（HSP70）抗体。结果过敏性紫癜组中HSP70抗体检测阳性率（70．3％）明显高于对照组（17．1％）,两者相比差异有显著性（P〈0．01）;过敏性紫癜肾炎型HSP70抗体阳性率（80％）高于非肾炎型（63．6％）,两者相比差异有显著性（P〈0．05）。结论HSP70参与了过敏性紫癜的发病过程,且可反应肾脏是否受累。     

过敏性紫癜患儿血清呼吸道病毒感染特异性IgM及炎症因子检测及临床意义

目的 检测过敏性紫癜患儿血清呼吸道病毒感染特异性免疫球蛋白M(IgM)及炎症因子的表达水平,分析其与过敏性紫癜发生的关系.方法 选取2020年2月至2021年2月在本院住院治疗的70例过敏性紫癜患儿为过敏性紫癜组(春夏季、秋冬季各35例),同期选取在本院进行常规体检的健康儿童70例作为对照组(春夏季、秋冬季各35例).采用间接免疫荧光法检测血清中常见呼吸道病毒的特异性IgM;采用酶联免疫吸附(ELISA)法检测血清炎症因子白细胞介素-27(IL-27)、白细胞介素-17(IL-17)、白细胞介素-6(IL-6)、同型半胱氨酸(Hcy)表达水平;并分析过敏性紫癜发生的相关影响因素.结果 过敏性紫癜组呼吸道病毒感染率41.43％,显著高于对照组15.71％(P<0.05);过敏性紫癜组血清中呼吸道合胞病毒、乙型流感病毒特异性IgM检出率显著高于对照组(P<0.05);过敏性紫癜组秋冬季血清中呼吸道合胞病毒、乙型流感病毒特异性IgM检出率显著高于春夏季(P<0.05).过敏性紫癜组血清IL-17、IL-6、Hcy表达水平显著高于对照组,IL-27表达水平显著低于对照组(P<0.05).Logistic回归分析显示,血清呼吸道合胞病毒感染、乙型流感病毒感染及血清IL-27低表达、IL-17和IL-6高表达是影响过敏性紫癜发生的危险因素(P<0.05).结论 过敏性紫癜患儿血清中呼吸道合胞病毒、乙型流感病毒检出率较高,秋冬季高于春夏季,且血清炎症因子IL-27表达水平降低,IL-17、IL-6、Hcy表达水平升高,呼吸道合胞病毒、乙型流感病毒感染及炎症因子IL-27、IL-17、IL-6均是影响过敏性紫癜发生的因素,提示检测上述指标可能为治疗该疾病提供一定的临床价值.     

过敏性紫癜患儿外周血单核细胞TLR2表达及与免疫应答的相关性

背景：Toll样受体及其信号通路在自身免疫性疾病、超敏反应、炎症反应、细胞凋亡及移植排斥反应中发挥重要的作用,其在过敏性紫癜患儿免疫发病机制中的地位尚未完全阐明。目的：探讨过敏性紫癜患儿外周血单核细胞TLR2的表达及其与免疫应答的相关性。方法：64例过敏性紫癜患儿分为2组,即过敏性紫癜无肾损害组(36例)、过敏性紫癜肾损害组(28例),选择同期入院的30例健康体检儿童设置为对照组,采用流式细胞术检测外周血单核细胞TLR2表达,荧光定量PCR技术检测外周血单核细胞TLR2 mRNA相对表达量, ELISA检测血浆干扰素γ、白细胞介素4水平, ELISA法测定Treg细胞分泌的转化生长因子β、白细胞介素10水平。结果与结论：过敏性紫癜组干扰素γ、干扰素γ/白细胞介素4水平均显著低于对照组(P < 0.05),白细胞介素4水平显著高于对照组(P < 0.05);过敏性紫癜组TLR2 mRNA和蛋白表达显著高于对照组(P < 0.05);过敏性紫癜肾损害组TLR2 mRNA和蛋白表达显著高于过敏性紫癜无肾损害组(P < 0.05);过敏性紫癜组患者白细胞介素10和转化生长因子β表达显著高于对照组(P < 0.05)。结果表明过敏性紫癜患儿外周单核细胞TLR2 mRNA及蛋白表达增高,且患儿存在免疫表达失衡现象,TLR2参与过敏性紫癜免疫发病机制,转化生长因子β表达量能够评估Treg的免疫应答,可作为过敏性紫癜患儿诊断、治疗及预后参考依据。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

可溶性血管细胞粘附分子1(sVCAM-1)在紫癜性肾炎发病中的作用探讨

目的:探讨血管细胞粘附分子-1(VCAM-1)在过敏性紫癜性肾炎(HSPN)发病中的作用,并观察其与白介素-6(IL-6)、免疫球蛋白E(IgE)在HSPN发病中的关系。方法:采用酶联免疫吸附法(ELISA)检测27例过敏性紫癜、35例紫癜性肾炎患儿(其中急性期16例,恢复期10例)及20例健康对照儿童的血清sVCAM-1、IL-6、IgE水平。结果:①紫癜性肾炎组较单纯过敏性紫癜组、正常对照组血清sVCAM-1均明显升高,且急性期高于恢复期及正常对照组,差异均有显著性意义(P均<0.001),肾炎组、单纯组分别与对照组比较,血清IL-6、IgE水平升高,差异有显著性意义(P<0.01),恢复期较正常对照组血清sVCAM-1、IL-6水平无很大变化,差异无显著性意义(P均>0.05)。②紫癜性肾炎组、单纯过敏性紫癜组sVCAM-1水平随血清IL-6、IgE水平升高而增加(相关系数分别为0.35、0.38,P均<0.01)。结论:sVCAM-1参与了过敏性紫癜、紫癜性肾炎的发病过程,且可反映其病情程度。     

Elevated serum BAFF levels in patients with autoimmune hepatitis

Serum cytokines are thought to be involved in autoimmune hepatitis (AIH) pathogenesis via immune dysregulation. B-cell activating factor belonging to the tumor necrosis factor family (BAFF) is a member of the tumor necrosis factor (TNF) superfamily and is known for its role in the survival and maturation of B cells. The aim of the study was to evaluate the serum levels of BAFF in patients with AIH and determine its relation to the clinical features of AIH. We examined serum BAFF levels in 55 patients with AIH, 14 patients with acute hepatitis (AH), 33 patients with chronic hepatitis C, and 33 healthy subjects by enzyme-linked immunosorbent assay. Liver function tests, quantitative immunoglobulin, and antinuclear antibody levels were also assayed in AIH patients. Serum BAFF levels were elevated in AIH patients compared with healthy subjects (AIH: 2.07+/-1.21 pg/ml, control: 0.77+/-0.22 pg/ml). Similarly, serum BAFF levels were significantly higher in AIH patients compared with AH or chronic hepatitis C patients. There was a positive correlation between BAFF and aspartate aminotransferase (r=0.513, p<0.0001), alanine aminotransferase (r=0.435, p<0.0001), total bilirubin (r=0.419, p<0.01), and soluble CD30 (r=0.579, p<0.0001) in AIH patients. However, there was no correlation between BAFF and levels of gammaglobulins or titer of antinuclear antibodies. Corticosteroid treatment resulted in marked reduction in serum BAFF levels in AIH patients. These results suggest that BAFF contributes to liver injury and disease development in AIH patients.     

Increase in B-cell-activation factor (BAFF) and IFN-gamma productions by tonsillar mononuclear cells stimulated with deoxycytidyl-deoxyguanosine oligodeoxynucleotides (CpG-ODN) in patients with IgA nephropathy

IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is recognized as a tonsil-related diseases since it often gets worse after and/or during acute tonsillitis and the disease progression is often prevented by tonsillectomy. Although several reports showed an increase in IgA production of tonsillar mononuclear cells (TMCs), its mechanism has not yet been fully clarified. Recently, B-cell-activation factor (BAFF), which stimulates B-cell proliferation and immunoglobulin production, was identified. Unmethylated deoxycytidyl-deoxyguanosine oligodeoxynucleotide (CpG-ODN), which is able to mimic the immunostimulatory activity of microbial DNA, is known to be involved in the production of immunoglobulins and some cytokines. In this study, we focused on roles of BAFF and IFN-gamma in IgA production of TMCs stimulated with CpG-ODN in IgAN patients. Two-color flow cytometric analysis revealed that the intercellular expression of IFN-gamma on the T-cells freshly isolated from tonsils was significantly higher in IgAN patients than in non-IgAN patients (p=0.032). The spontaneous productions of IgA and IFN-gamma of TMCs were significantly higher in IgAN patients than in non-IgAN patients (p=0.023 and p=0.02). Under stimulation with CpG-ODN, the productions of IgA, BAFF and IFN-gamma of TMCs were significantly higher in IgAN patients than in non-IgAN patients (p=0.013, p=0.005 and p=0.039). The IgA production of TMCs stimulated by CpG-ODN was inhibited by the treatment with anti-BAFF antibody and/or anti-IFN-gamma antibody. Under stimulation with IFN-gamma, the BAFF expression on the CD1c cells and the BAFF production of TMCs were significantly higher in IgAN patients than in non-IgAN patients (p=0.004 and p=0.042). These data suggest that hyper-immune response to microbial DNA may be present in IgAN patients and may lead to hyperproduction of BAFF up-regulated by IFN-gamma, resulting in hyperproduction of IgA in IgAN patients.     

南京地区过敏性紫癜患儿血清过敏原特异性IgE结果分析

目的 回顾性分析南京医科大学附属儿童医院过敏性紫癜(Henoch-Schonlein purpura,HSP)患儿的过敏原检测情况,为临床诊治提供参考。方法 采用德国MEDIWISS过敏原体外检测系统,检测本院最近四年内接诊的1026例HSP患儿的血清过敏原特异性免疫球蛋白E(specific immunoglobulin E,sIgE)的含量。结果 432例HSP患儿血清sIgE检出为阳性,阳性率为42.11%(432/1026),该432例HSP患儿血清过敏原sIgE分布以1~2级为主,学龄组患儿血清过敏原sIgE阳性率占总人数的65.74%(284/432),远高于婴幼儿组(27例)和学龄前组(121例)(F值分别为7.71和4.05,P值均<0.05)。结论 患儿体内sIgE水平不同程度的增高对HSP的诊治具有一定意义。控制患儿与过敏原接触是防治HSP的关键。     

BAFF and BAFF-R of peripheral blood and spleen mononuclear cells in idiopathic thrombocytopenic purpura

BAFF (B-cell activating factor belonging to the TNF family) is an essential component of B-cell homeostasis, and is required for the normal survival and development of B cells. To further explore the role of this cytokine in the pathogenesis of idiopathic thrombocytopenic purpura (ITP), BAFF/BAFF-R (one of receptors of BAFF) expression levels were determined and the correlation between the clinical parameters and the BAFF expression levels was analyzed. A total of 57 patients with ITP were enrolled and 25 age and sex-matched healthy volunteers served as controls. Serum was obtained from 41 patients with ITP and 22 healthy volunteers and was analyzed with a commercial human soluble BAFF (sBAFF) ELISA kit. BAFF and BAFF-R mRNA expression of peripheral blood (PB) (n = 42) and splenocytes (SP) (n = 8) mononuclear cells (MNC) were determined by real-time quantitative PCR. The SPMNC of normal controls came from three hereditary spherocytosis patients who underwent splenectomy. The untreated patients with ITP had higher serum BAFF levels (Median 1430 pg/ml, Range: 534–5787 pg/ml) than those of normal controls (Median 1120 pg/ml, Range: 640–2376 pg/ml, p = 0.006) and treated ITP group (Median 662 pg/ml, Range 267–1265 pg/ml, p = 0.000). On the other hand, serum BAFF levels of treated patients with ITP were lower than those of normal controls (p = 0.001). There was a weak correlation (the Pearson correlation coefficient is ? 0.242) between platelet count and BAFF (p = 0.064). However, BAFF levels did not correlate with platelet associated immunoglobulin or immunoglobulin levels. Moreover, the serum BAFF levels were not statistically different between acute and chronic ITP (p = 0.841). PBMNC of ITP had higher BAFF but not BAFF-R mRNA expression than that of normal controls. BAFF mRNA expression of SPMNC had a positive correlation with BAFF-R in ITP patients but not in PBMNC of normal controls and untreated ITP patients. The BAFF-R mRNA expression of SPMNC was shown to be 15.29 times higher than that of PBMNC in ITP. BAFF might contribute to autoimmunity and disease development in ITP. However, BAFF serum level must be carefully considered as a surrogate marker of disease activity in ITP.     

系统性红斑狼疮患者血清BAFF和IL-21的变化及意义

目的：探讨系统性红斑狼疮患者血清BAFF和IL-21水平的变化意义。方法：采用酶联免疫吸附试验的方法（ELISA）对血清中两种物质进行检测。结果：系统性红斑狼疮患者血清BAFF和IL-21高于对照组；狼疮肾炎肾活检组中BAFF随病理改变加重而升高，IL-21在Ⅱ、Ⅲ型、Ⅳ型狼疮肾炎中有升高，但在Ⅳ型中改变最明显；狼疮伴干燥综合症改变组BAFF和IL-21均增加明显；应用糖皮质激素治疗1周后的患者血清BAFF和IL-21水平均呈下降趋势，但以BAFF下降最明显；系统性红斑狼疮患者血清BAFF和IL-21的变化与患者体内的主要免疫指标变化相关；在Ⅳ型狼疮肾炎患者中BAFF和IL-21的变化呈正相关。结论：系统性红斑狼疮患者血清BAFF和IL-21均增加，T、B淋巴细胞异常功能及协同作用在不同脏器的损伤和不同的病理过程中，各自发挥作用的程度不同。     

Elevated levels of anti-Helicobacter pylori antibodies in Henoch-Schönlein purpura

OBJECTIVE: Henoch-Schonlein purpura (HSP) is a systemic vasculitis characterized by IgA-containing deposits in the skin, joints, gastrointestinal mucosa and glomeruli. HSP is much rarer in adults than in children. Among a number of other pathogenic factors, Helicobacter pylori (Hp) has recently been implicated in the gastrointestinal and extra-gastrointestinal manifestations underlying HSP. We aimed at studying the occurrence of Hp infections in 11 adult HSP patients with appearance in our clinical practice in the last 5 years. METHODS: Eleven adult HSP and 20 healthy adult patients were recruited for this study. Anti-Hp IgG and IgA antibodies were assessed in sera of HSP patients with active (n = 5) and remittent disease (n = 6) and healthy controls (n = 20) in the context of clinical symptoms, endoscopic evaluation, as well as routine and immunolaboratory observations. Concurrent Hp infection was confirmed by urease test and histology. RESULTS: Anti-Hp antibodies were present in 10/11 of HSP patients, and 11/20 of healthy controls. However, only 4/11 HSP patients had concurrent Hp infection as confirmed by urease test and/or histology. In the healthy controls the actual Hp infection was detectable in 9/20 cases. Patients in the acute phase had significantly higher levels of anti-Hp IgG compared to healthy controls (86.0 +/- 32.0 versus 25.5 +/- 28.5 U/ml, p < 0.05). In contrast, anti-Hp IgA/IgG ratios were significantly higher in the remitting phase compared to the control group (3.1 +/- 1.8 versus 0.8 +/- 0.5 ratio, p < 0.05). Among other immunolaboratory markers, serum CRP, circulating IgA and serum tumor necrosis factor-alpha levels were significantly increased in acute patients compared to healthy group results (45.3 +/- 22.7 versus 4.8 +/- 3.5 mg/l, p < 0,05); (58.9 +/- 18.2 versus 25.2 +/- 6.4pg/ml, p < 0,05); (5.5 +/- 1.1 versus 2.4 +/- 1.2 g/l; respectively, p < 0.05). CONCLUSIONS: Hp infection may be associated with the development and progression of HSP. IgG antibodies to Hp may be present mostly in acute HSP, while IgA antibodies may be involved in sustaining gastrointestinal symptoms underlying the chronic phase of the disease.     

BAFF is elevated in serum of patients with Wegener's granulomatosis

BAFF (B-cell activating factor of the TNF family) plays a crucial role in B-cell survival. Elevated BAFF serum levels have been linked to several autoimmune diseases in humans, and therapies targeting BAFF were successful in animal models of rheumatoid arthritis and systemic lupus erythematosus. Wagener's granulomatosis (WG), a chronic systemic vasculitis, is characterized by circulating autoantibodies (cANCA) targeting neutrophils, which can produce BAFF. To investigate whether BAFF is involved in WG pathology, BAFF serum levels were measured by ELISA in 46 WG patients and 62 healthy donors. We report the novel finding that in WG patients serum levels of BAFF were significantly increased (median 3.95 ng/ml, p=0.009) compared to healthy controls (median 2.38 ng/ml). The difference was even more pronounced when comparing controls with untreated WG patients (median 4.61 ng/ml, p=0.001). Treatment of WG patients with glucocorticoids was associated with lower BAFF levels. The serum BAFF level in treated WG patients was about the same as in the control group. We propose that BAFF might be a pathogenic factor in WG and that targeting BAFF may represent a new therapeutic strategy in a subset of chronically relapsing WG patients with elevated BAFF levels.     

B cell activating factor (BAFF) in the natural history of chronic hepatitis C virus liver disease and mixed cryoglobulinaemia

B cell activating factor (BAFF) plays a crucial role in the process of development, maturation and activation of B lymphocytes. Chronic hepatitis C virus (HCV) infection is characterized by multiple B cell disorders. It is a major cause of type II mixed cryoglobulinaemia (MC). We measured serum BAFF levels in several clinical situations to elucidate the potential role of BAFF in chronic HCV infection. We used a commercially available solid phase enzyme-linked immunosorbent assay. We estimated serum BAFF in stored sera from uninfected controls (n = 8), patients with chronic hepatitis B virus infection HBV (n = 5) and chronic HCV infection with (n = 16) and without mixed cryoglobulinaemia (n = 14). In two patients with HCV and MC we correlated BAFF with HCV RNA after pegylated interferon (peg-I). We correlated serum BAFF levels at baseline and at 12 weeks with treatment response: sustained virological response SVR (n = 5), non-responders (n = 6) and relapsers (n = 2). Finally, we estimated BAFF levels after complete depletion of B cells with rituximab in patients with chronic HCV with MC (n = 3). Serum levels of BAFF were increased in chronic HCV with MC, but not in chronic HBV infection, suggesting an association between BAFF and cryoglobulinaemia. Peg-I increased BAFF levels in serum and this paralleled HCV RNA very closely. Serum BAFF levels at week 12 of therapy with peg-I and R were significantly higher in responders than non-responders. Finally, B cell depletion was associated with markedly increased levels of BAFF.