Immune therapy of lupus: what is on the horizon?

Systemic lupus erythematosus (SLE) is a complex disease whichhas posed a continuing challenge to scientists and cliniciansof diverse areas of specialization. It serves as a model forthe study of the mechanisms of autoimmunity—providingan important basis for the development of novel targeted therapiesin lupus and related conditions. The pathophysiology of SLE stems from the abnormal clearanceof apoptotic cells and/or endothelial activation. Material fromdying cells such as apoptotic blebs that are not efficientlyremoved may act as antigenic stimuli and lead to the developmentof autoantibodies with consequent formation of immune complexesand an inflammatory response in a variety of organ systems [1].This     

系统性红斑狼疮的肺胸膜损害

分析了系统性红斑狼疮并肺、胸膜损害30例,胸膜改变占首位,共19例,(63.3％),其中胸膜积液16例,合并心包积液3例。其次为SLE肺炎5例(16.7％),尿毒症肺水肿3例(10％),弥漫性肺间质纤维化2例(6.7％),肺不张1例(3.35％)。对临床表现、诊断、治疗和预后进行了讨论。     

关木通引起慢性间质性肾炎7例报告

目的　观察关木通所致慢性肾损伤的临床和病理改变特点。方法　本组 7例中 ,男 5例 ,女 2例。 3例服关木通汤药 ,4例服含关木通成药。分析服用时间、累积总量与肾损害首发症状及症状出现时间、肾功能和肾病理改变的关系。结果　汤药组 :服药时间平均 3 3 3个月 ,累积总量平均 82 9 3 g ,首发症状为乏力 3例 ,夜尿增多 2例 ,平均时间为 8 3个月 ,Cr平均 40 2 μmol/L。肾病理 :3例均为重度寡细胞性肾间质纤维化 ,肾小管广泛萎缩。成药组 :服药时间平均 7 5个月 ,累积总量平均 13 6g ,乏力 3例 ,夜尿增多 1例 ,恶心呕吐、头痛头晕 1例 ,平均18 8个月 ,Cr 3 62 8μmol/L。肾病理为重度寡细胞性间质纤维化和灶状纤维化各 2例 ,肾小管灶状萎缩 3例 ,广泛萎缩 1例。结论　汤药组关木通积累大 ,发病时间早 ,肾病理改变重。提示关木通所致肾损其临床表现、病理改变与服用关木通时间、剂量相关。     

系统性红斑狼疮女性患者血清CA125,CA199化学发光法测定的临床应用

目的 :探讨系统性红斑狼疮 (SLE)女性患者血清肿瘤标志物CA12 5 ,CA199含量变化及临床意义。方法 :用化学发光法测定 30例正常女性和 38例SLE女性患者血清中CA12 5 ,CA199含量。结果 :正常组CA12 5含量为 11.14± 6 .4 8U/ml,CA199含量为 3.75± 2 .89U/ml;SLE组CA12 5 ,CA199分别为 2 2 .5 6± 2 0 .4 6U/ml,9.5 7± 9.34U/ml。SLE患者CA12 5 ,CA199阳性率分别为 2 1.1% ,7.89%。结论 :SLE患者血清CAl2 5 ,CA199含量较正常组增高 (P <0 .0 5 )。CA12 5 ,CA199在SLE女性患者中可出现阳性 ,对临床诊断SLE有一定价值。     

肾间质纤维化组织来源成纤维细胞血管紧张素Ⅱ1A受体的表达及其生物学意义

用单侧输尿管梗阻的方法诱导小鼠肾间质纤维化，并从中成功地培养出了成纤维细胞。对成纤维细胞血管紧张素Ⅱ１Ａ（ＡＴ１Ａ）受体的表达与细胞增殖和分泌细胞外基质的关系进行了研究。结果发现，从肾间质纤维化组织中培养出的成纤维细胞，细胞增殖和产生纤维连接蛋白及层粘连蛋白的能力明显高于从正常肾间质中培养的成纤维细胞。在单侧输尿管梗阻小鼠的血浆和肾组织中血管紧张素Ⅱ的活性显著升高。从肾间质纤维化组织中培养出的成纤维细胞，ＡＴ１Ａ受体的表达在蛋白质和分子水平上均有明显增高。表明，在肾间质纤维化过程中肾素－血管紧张素系统被激活，对刺激成纤维细胞增殖和产生细胞外基质起着重要作用。     

Infantile chronic tubulo-interstitial nephritis with cortical microcysts: variant of nephronophthisis or new disease entity?

Over a 15-year period we observed seven children (four girls, three boys) who presented within the first months of life with severe renal failure and acidosis, associated with hypertension in five patients and polyuria in four. In addition, one patient had a severe cholestatic liver disease. In two families, a similarly affected sibling had died previously. Four patients were referred with the clinical diagnosis of polycystic kidney disease because of moderate enlargement of kidneys, but renal imaging (intravenous pyelography and ultrasonography) did not confirm this diagnosis. A renal biopsy, performed in all patients, showed similar features characterized by a diffuse chronic tubulo-interstitial nephritis (TIN) and particularly by the presence of microcystic dilatation of proximal tubules and Bowman's space. Liver pathology was normal in two patients, including one with hepatomegaly. However, in the patient with cholestasis there was inflammatory portal fibrosis with mild duct proliferation. Progression of the renal disease was extremely rapid and all patients reached end-stage renal failure (ESRF) before the age of 2 years (11–22 months). Two children had successful renal transplants. Although this chronic TIN shares some features with nephronophthisis, we suggest that it represents a distinct entity both on clinical and morphological grounds. The specific clinical features of this disease are its early onset and rapid progression to ESRF. Pathologically, it differs from nephronophthisis by the absence of medullary cysts and thickened tubular basement membranes and by the presence of cortical microcysts.     

Immunoadsorbent apheresis eliminates pathogenic IgG in childhood lupus nephritis

BACKGROUND: It is suggested that the highly cation-charged fraction of the IgG and IgG3 subclasses may play a pathogenic role in lupus nephritis. In contrast, immunoadsorbent therapy using a sodium dextransulfate fixed cellulose gel column-low invasive selective immunoadsorbent apheresis therapy (SDSC-IAT) has been applied to lupus nephritis with favorable results. However, elimination using pathogenic IgG by SDSC-IAT has never been investigated. METHOD: Two patients with diffuse proliferative lupus nephritis were treated using SDSC-IAT concomitant with immunosuppressive therapy. The eluates from the SDSC, and the patients' serum obtained before and just after SDSC-IAT were subjected to an IgG charge analysis using isoelectric focusing and immunoblotting, and also to laser nephelometry assay, which is used for measuring IgG subclass concentration. Indirect immunofluorescence staining was performed to detect IgG subclass deposition in the glomerulus. RESULTS: Both of the patients had an immediate decrease in anti-double-strand DNA antibody and in the circulating immune complex with a following clinical improvement. Repeated biopsies demonstrated improvement of glomerular lesions with a marked reduction of IgG and C3 deposition. The IgG of the SDSC eluates consisted of highly cation charged (isoelectric points: 9-10) fractions. In addition, IgG3 was specifically removed from the patients' serum using an SDSC among the IgG subclasses. The subclass of deposited IgG in the glomeruli showed IgG3 predominance. CONCLUSION: SDSC-IAT specifically removed the highly cation charged fractions of IgG and IgG3 from the patients' serum and the elimination of these fractions may have resulted in clinical improvement.     

C_3基因在BXSB小鼠主要脏器中的表达

用同位素标记ｃＤＮＡ探针的分子杂交方法检测了ＢＸＳＢ小鼠肝、肾、脾、胸腺各脏器中补体Ｃ_３ｍＲＮＡ的表达情况，结果表明３～４月龄雄性ＢＸＳＢ小鼠肝、肾、脾各脏器Ｃ_３ｍＲＮＡ的表达量较正常对照鼠显著增加。Ｃ_３基因的过度表达可能参与ＢＸＳＢ小鼠ＳＬＥ多脏器非感染性炎症的发生，同时提示该鼠存在Ｍ系统的大量扩增及活化。