Anti-ribosomal P antibodies and lupus nephritis

Increasing attention has been paid to the relationship of autoantibodies to ribosomal P proteins (anti-P) with lupus nephritis. Several mechanisms of involvement of anti-P in lupus nephritis have been proposed, including cross-reactivity with anti-dsDNA and anti-endothelial cell antibodies (AECA). In addition, it is also suggested that anti-P might play a role in the development of lupus nephritis through induction of T helper 1 responses. Of note, recent studies have disclosed that the presence of isolated anti-P antibodies may discriminate patients with pure class V lupus nephritis, whereas the simultaneous presence of anti-dsDNA antibodies suggests class V disease with concomitant proliferative lesions. These observations lead to the hypothesis that anti-P and anti-dsDNA might result in membraneous changes and proliferative changes, respectively, although further investigation is required for confirmation.     

Antiphospholipid antibodies in patients with lupus nephritis

The aim of this study was to compare the prevalence of anticardiolipin antibodies with other types of antiphospholipid antibodies (aPL) (antiphosphatidylserine--aPS, antiphosphatidylinositol--aPI, antiphosphatidylethanolamine--aPE) in patients with lupus nephritis and to find if the examination of a panel of various aPL is valuable for further diagnosis of patients. Additionally we determined the levels of autoantibodies against beta2-glycoprotein I (beta2GPI) and oxidized low-density lipoprotein (anti-oxLDL) and also investigated the relationship between antibodies against beta2GPI and oxLDL, which were assessed by ELISA methods. Twenty-two patients with lupus nephritis were studied. The control group consisted of 62 healthy blood donors. A statistically significant higher occurrence of all aPLs in the patients with lupus nephritis in comparison to the control group was found. The prevalence of polyspecific antibodies, which reacted with at least two various phospholipids, was 82% in the group of SLE patients. Significantly higher levels of IgG anti-beta2GPI in the sera of SLE patients (p = 0.0003) was detected. The levels of anti-oxLDL in the sera of the patients group did not differ significantly from the control one. Some positive samples for anti-beta2GPI and negative for aCL or anti-oxLDL and vice versa were found. It ca be concluded that the production of aPL including anti-beta2GPI and anti-oxLDL in the lupus nephritis patients is higher in comparison with healthy blood donors. We assume that the estimation of various types of aPL may be important in the selection of the group patients with renal diseases. The synthesis of aPL can reflect the spreading of the autoimmune response for several antigens modified on the vessel wall.     

T and B lymphocyte function in patients with lupus nephritis: correlation with renal pathology

The relationship between in vitro measures of T and B cell responses of peripheral blood lymphocytes and histological findings on renal biopsy was examined in 32 patients with lupus nephritis. T cell mediated responses, assessed by mixed leucocyte reaction (MLR) and cell mediated lympholysis (CML), were decreased, while spontaneous immunoglobulin secretion by B cells, measured by plaque forming cell (PFC) assay, was increased above normal in the whole patient population. There were no significant differences in these T or B cell responses between patients with the diffuse proliferative and the membranous forms of lupus nephritis. Using a semi-quantitative index of the histologic activity of diffuse proliferative lupus nephritis, a good correlation was noted between the degree of abnormality of B cell responses and the level of activity seen on renal biopsy. The nature of the relationship between B cell abnormalities and the expression of lupus nephritis warrants further study.     

抗C1q抗体与狼疮性肾炎

系统性红斑狼疮(SLE)患者血清中超过150种自身抗体,研究发现SLE病人血清有另一种重要的补体成分C1q的抗体,即抗C1q抗体.该抗体普遍存在于SLE病人血清中,并与肾脏受累有关,且抗体滴度增加提示肾炎复发.本文就抗C1q抗体在狼疮性肾炎(LN)诊断、随访、早期识别狼疮活动以及复发等方面作用作一综述.     

T cells and B cells in lupus nephritis

T and B lymphocytes play diverse roles at multiple stages in the development and progression of lupus nephritis. Disruption of T- and B-cell regulatory functions by environmental and genetic influences permits pathogenic effectors to emerge in disease. New insights into the biology of these multifunctional cells offer novel targets for intervention in lupus nephritis and systemic autoimmunity.     

Cellular infiltrate in renal graft rejection: T lymphocyte subsets detected by monoclonal antibodies

We have examined the interstitial cellular infiltrate using monoclonal antibodies against T cells (Cris 1), helper/inducer T cells (OKT4) and suppressor/cytotoxic T cells (OKT8) by indirect immunofluorescence in renal biopsies taken from 14 transplanted patients during clinical episodes suggestive of acute (n = 9), chronic (n = 2) and no rejection (n = 3). Infiltrating T cells and T cell subsets were found to be significantly increased during all types of rejection (n = 11) as compared to no rejection (n = 3). Two types of biopsies could be distinguished according to the predominance of T cell subsets. In some biopsies (n = 6), OKT8+ cells were significantly more numerous that OKT4+ cells. In the remaining biopsies (n = 5), OKT4+ cells were more common that OKT8+ cells, the OKT4/OKT8 ratio being significantly higher. No association was observed between HLA mismatch and predominating T cell subset, neither for type nor outcome of graft rejection. Our results suggest that the OKT4+ cells may play a more important role than previously reported in renal graft rejection.     

Anti-DNA antibodies in the urine of lupus nephritis patients.

BACKGROUND: It has previously been reported that patients with systemic lupus erythematosus (SLE) and glomerulonephritis do not have anti- (deoxyribonucleic acid) DNA antibodies in their urine. This finding was attributed to specific entrapment of anti-DNA antibodies by the immune complexes in the glomerular capillary walls. METHODS: This phenomenon has been re-investigated as part of a study of the use of desoxyribonuclease 1 (DNase 1) to treat lupus nephritis (LN). For this purpose an ELISA was developed for the detection of anti-DNA antibodies in urine. It was found that such an assay was very susceptible to the presence of DNase in urine which destroys the antigen coating the plates and gives rise to false negative results. For this reason, it is essential that all tests for anti-DNA antibodies in the urine are carried out in the presence of EDTA to inhibit the endogenous DNase 1 activity. RESULTS: Using this assay to test the urine from 24 patients with LN and non-selective proteinurea, it was found that they all contained anti-DNA antibodies. The amount of anti-DNA antibodies detected in the urine was compared with that expected by calculations from the anti-DNA antibody titre in the serum and total immunoglobulin levels in serum and in urine. It showed that in 20 patients there was neither specific entrapment nor specific excretion of anti-DNA in urine, only the expected amount of leakage. In only three patients was any appreciable entrapment demonstrated and in only one, any excess excretion. CONCLUSIONS: It is suggested that the failure to detect anti-DNA antibodies in the urine in the previous work was due to failure to inhibit the endogenous urinary DNase. It remains to be determined whether the retention of anti-DNA antibodies or excessive secretion is correlated with clinical phases of LN.     

抗核小体抗体与狼疮肾炎活动性关系的研究

目的探讨抗核小体抗体与狼疮肾炎活动性的关系。方法对2007年4月至2009年12月在我院住院的75例经肾活检确诊为狼疮肾炎患者的临床资料进行回顾性研究。结果抗核小体抗体在活动性增殖性狼疮肾炎中的阳性率（59．3％）较非活动性增殖性狼疮肾炎（27．3％）和非增殖性狼疮肾炎（20．0％）高（P〈0．05）。活动性狼疮肾炎组的抗核小体抗体阳性率（53．8％）较非活动性狼疮‘肾炎组阳性率（23．8％）高（P〈0．05）。抗核小体抗体阳性组的病理活动性指数（active index,AI）较阴性组高（P〈0．05）,两组慢性指数（chronic index.CI）和狼疮肾炎的临床活动性评分（renalactivity score,RAS）无显著差异（P〉0．05）。结论抗核小体抗体与狼疮肾炎的病理活动性相关,在活动性增殖性狼疮肾炎中出现较为普遍,是提示活动性增殖性狼疮肾炎的一项重要的指标。     

Hemichorea with antiphospholipid antibodies in a patient with lupus nephritis

Although central nervous system involvement is an important manifestation of systemic lupus erythematosus (SLE), chorea is a relatively uncommon complication. A strong association between chorea and the presence of antiphospholipid antibodies (aPLs) has been reported in patients with SLE, lupus-like disease, or primary antiphospholipid syndrome. We describe a patient with lupus nephritis and cerebral infarction, who subsequently developed recurrent hemichorea associated with increased aPLs levels. A 7-year-old boy suffered from lupus nephritis and a left middle cerebral artery infarction associated with aPLs. He subsequently experienced two episodes of right hemichorea associated with increased aPLs levels without any evidence of further neurological lesions by brain computed tomography or magnetic resonance imaging. The previous left cerebral artery infarction might have increased the susceptibility of the left basal ganglia to the effects of aPLs that contributed to the development of the right hemichorea in this patient.     

Significance of anti-phospholipid antibodies in patients with lupus nephritis.

Anti-phospholipid antibodies (APA) as markers or mediators of thrombosis in lupus could be of pathogenetic significance in nephritis, since glomerular capillary thrombi are an indicator of subsequent renal dysfunction. Isotype specific APA antibodies were measured, using cardiolipin as the antigen, in 76 patients with lupus nephritis. Twenty-nine percent of the patients had elevated IgG APA. Overall, 43% of patients showed raised levels of at least one isotype. In general, APA had specificity for anionic phospholipids. In vitro lupus anticoagulant activity was associated with all three isotypes of APA, but only the IgM isotype correlated with the biological false positive test for syphilis. APA were not associated with thromboses or neurological involvement, and only the IgA isotype correlated with thrombocytopenia. We confirmed an association between the presence of intraglomerular thrombi and serum IgG APA. However, we found no association between APA and renal histological pattern, or long-term renal function. Our data, therefore, do not support a major pathogenetic role for APA in the nephritis of lupus in treated patients.     

手足口病患儿T淋巴细胞亚群检测和分析

手足口病是一种常见的儿童传染病,全年均可发生,但多流行于夏秋季节。本病多发生于5岁以下的婴幼儿,可引起发热和手、足、口腔等部位的皮疹和溃疡,个别可引起心肌炎、肺水肿等致命性并发症,流行时可出现较高病死率H引。该病的病原主要为小RNA病毒科,柯萨奇病毒（A组16、4、5、7、9、10型及B组2、5、13型）,埃可病毒和肠道病毒71型,其中以柯萨奇病毒A16型及肠道病毒71型最为常见。     

肺移植术后T细胞亚群研究进展

T细胞是肺移植术后免疫应答的主要效应细胞,其细胞亚群水平对肺移植受者机体免疫状态具有重要影响。本文综述CD4^＋ T细胞、CD8^＋ T细胞和调节性T细胞的免疫学机制及其与肺移植术后原发性移植肺功能障碍、排斥反应、免疫耐受和感染等的关系,同时探讨监测肺移植术后T细胞亚群的临床意义。     

Antisperm antibodies and lymphocyte subsets in semen—not a simple relationship

The significance of white blood cells in the ejaculate remains a matter of controversy. Several authors have suggested that such cells are important in the modulation of an antisperm antibody response, i.e. a predominance of suppressor/cytotoxic to helper/inducer T cells may prevent the development of antisperm antibodies. In order to examine this relationship further we have documented the white blood cell types, with emphasis on the T-lymphocyte populations, in the ejaculates of men from infertile couples with and without antisperm antibodies; the latter group was divided further into two groups--vasovasostomized men and idiopathic men. All seven of the men without antisperm antibodies had a predominance of suppressor/cytotoxic T cells to helper/inducer T cells in the ejaculate. However, only in some of the men with antibodies was there a predominance of T-helper/inducer cells. It is clear that the relationship between antisperm antibodies and seminal leucocytes is therefore not as straightforward as has been proposed.     

Quantitative bone histomorphometry and circulating T lymphocyte subsets in postmenopausal osteoporosis

To explore the influence of the immune system on the development of osteoporosis, 19 untreated postmenopausal women with osteoporosis were studied by means of quantitative histomorphometry of the ilium and an analysis of T lymphocyte subsets in the peripheral blood. Osteoporotic women had lower OKT3+ and OKT8+ counts and a higher OKT4+/OKT8+ ratio than nonosteoporotic control subjects. Linear regression analyses disclosed that the age of subjects correlated with bone mineral density (BMD; r = -0.634, p less than 0.01) and some of the histomorphometric parameters for bone formation (r = -0.694 to -0.467, p less than 0.01-0.05). The number of OKT4+ cells showed weak but significant negative correlation with the parameters for bone resorption (r = -0.549 to -0.462, p less than 0.05). In a multiple regression analysis, the advanced age, the increase in OKT3+, and the decrease in OKT4+ and OKT8+ counts were shown to be significant predictors for the decrease in BMD (R = 0.882, p less than 0.01). According to the regression formula obtained from the analysis, the parameters for bone formation were related only to the age of subjects whereas those for bone resorption were tightly associated with the number of OKT4+ and OKT8+ cells but not with the age of subjects. These results indicated that, in addition to the age factor, abnormalities of the peripheral T lymphocyte subsets, especially those of OKT4+ and OKT8+ cells, are closely associated with the decrease in bone mass in postmenopausal osteoporosis, supporting the causal relationship between T lymphocyte functions and the development of postmenopausal osteoporosis.     

大鼠同种异体肢体移植中T淋巴细胞亚群的变化及其意义

目的 建立大鼠同种异体肢体移植模型，研究肢体移植中T细胞亚群的变化及其与急性排斥反应的关系。方法 将31只SD雄性大鼠随机分成两组，其中对照组14只为Wista→SD肢体移植术后不用药组，实验组17只为FK506(4mg／kg体重) RS-61443(30mg／kg体重)联合免疫抑制治疗组，观察各组移植术后排斥反应；用免疫荧光染色流式细胞仪检测各组手术前后T细胞亚群。结果 术后第3天，CD4／CDs比值显著增高，移植肢体开始出现肿胀、皮肤红斑等表现；CD4／CD8比值增高与排斥反应程度呈正相关，而用药组术后，CD4／CD8较术前无明显变化，未出现排斥反应。结论 T细胞亚群中CD4／CD8比值的变化与肢体移植急性排斥反应的发生、强烈程度有密切关系，可作为监测异体肢体移植急性排斥反应的免疫学指标。     

Heterogeneity of immune complex-derived anti-DNA antibodies associated with lupus nephritis

The mechanisms responsible for the tissue injuries associated with lupus nephritis have not yet been well explained. We have investigated the characteristics of anti-DNA antibodies in circulating immune complexes (CIC) and in the deposits of renal glomeruli in patients with active lupus nephritis. The CIC-derived antibodies expressed anti-DNA idiotypes (Id) designated as 0-81 Id and NE-1 Id, and bound mainly to single-stranded DNA but never to glomerular basement membrane (GBM) antigens. On the other hand, the immunoglobulins (Ig) eluted from renal glomeruli of lupus patients reacted not only with DNA but also with GBM, proteoglycan, and heparan sulfate. The binding of glomeruli-deposited Ig was markedly low when GBM antigens were used after treatment with heparitinase, suggesting that some anti-DNA antibodies may bind directly to GBM antigens associated with heparan sulfate, and form in situ IC in renal glomeruli. It was also revealed that the renal eluates obtained after passing through GBM antigen-coupled Sepharose lost the binding ability with GBM but still retained DNA-binding and 0-81 Id activity, showing the participation of circulating IC-derived anti-DNA antibodies in the glomerular deposits. Theoretically there may be two mechanisms in the pathogenesis of lupus nephritis through the deposition of circulating IC and through in situ formation of anti-DNA IC in renal glomeruli. The diversity of histological features in lupus kidneys may be attributed to the heterogeneity of the mechanisms.     

大鼠异体肢体移植中淋巴细胞亚群的动态观察

目的 探讨大鼠后肢异体移植中排斥反应与T淋巴细胞亚群和活化T细胞的关系。方法 将24只（8只Wistar，16只SD）大鼠随机分成两组，实验组8只为Wistar-→SD后肢移植未作免疫抑制组，对照组8只为FK506（2mg／kg体重）和霉酚酸（20mg／kg体重）免疫抑制组，观察术后排斥反应及病理检查；流式细胞仪检测T细胞亚群和活化T细胞。结果 术后6～8d，实验组移植肢体出现排斥反应，活化T细胞（CD3／CD69、CD3／CD25、CD3／HLA-DR）已于排斥反应发生（6．88±0．83）d前2—4d显著升高，CIM／CD8比值中度升高；活化T细胞增高与排斥反应程度呈正相关（相关系数r为0．874、0．854、0．879，P〈0．05）；CIM／CD8比值与排斥反应程度无明显相关（相关系数r=0．544，P〉0．05）；对照组，活化T细胞较术前无明显变化，未出现排斥反应。结论 动态监测活化T细胞将有助于异体肢体移植急性排斥反应的早期诊断。     

急性胰腺炎病人T淋巴细胞亚群改变与差异性凋亡

目的 动态观察急性胰腺炎(AP)病人T淋巴细胞亚群的变化及凋亡情况.方法 应用流式细胞仪三色荧光分析对44例轻型急性胰腺炎(MAP)病人和32例重症急性胰腺炎(SAP)病人发病第1、3、7天外周血T淋巴细胞CD4+、CD8+两个亚群各自的比例变化与凋亡情况进行动态监测.结果 与MAP组及健康对照组相比,SAP组病人在整个观察期内CD4+T细胞明显减少,CD4+/CD8+比值明显下降;同时发现CD4+T细胞的凋亡率明显增加,与上述二者的变化呈显著负相关.MAP组上述各指标呈一过性改变.而CD8+T细胞凋亡率在各组间及组内不同时点均无显著差别.结论 AP病人,特别是SAP病人病程中T淋巴细胞CD4+、CD8+两个亚群发生差异性凋亡,从而导致严重而持久的细胞免疫功能抑制,这可能是SAP病程中后期容易发生严重感染的重要原因.