Evaluation of the Japanese-Chinese Herbal Medicine,Kampo, for the Treatment of Lupus Dermatoses in Autoimmune Prone MRL/Mp-lpr/lpr Mice

Kampo, a Japanese-Chinese traditional herbal medicine, has been used for the treatment of various diseases for about 3,000 years in China. Among herbal medicines, Sairei-to is well known for improving the symptoms of rheumatoid arthritis (RA) and other collagen diseases. However, its immunosuppressive effects on autoimmune cutaneous phenomena are not completely understood. We investigated the effects of Sairei-to on the development of lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mice, an animal model which spontaneously develops skin lesions similar to those seen in human lupus erythematosus. Virgin female MRL/lpr mice at 1 month of age, which were treated orally with Sairei-to, had reduced amounts of IgG deposition at the dermoepidermal junction, titers of anti-DNA antibodies and rheumatoid factor, and lymphoproliferation. These results support the use of traditional herbal medicines in patients with human RA and systemic lupus erythematosus.     

Mycobacterium Tuberculosis Infection Incidence in Hospitalized Renal Transplant Patients in the United States, 1998–2000

The incidence, risk factors, and prognosis for Mycobacterium tuberculosis (MTB) infection have not been reported in a national population of renal transplant recipients. We performed a retrospective cohort study of 15,870 Medicare patients who received renal transplants from January 1, 1998 to July 31, 2000. Cox regression analysis derived adjusted hazard ratios (AHR) for factors associated with a diagnosis of MTB infection (by Medicare Institutional Claims) and the association of MTB infection with survival. There were 66 renal transplant recipients diagnosed with tuberculosis infection after transplant (2.5 cases per 1000 person years at risk, with some falling off of cases over time). The most common diagnosis was pulmonary TB (41 cases). In Cox regression analysis, only systemic lupus erythematosus (SLE) was independently associated with TB. Mortality after TB was diagnosed was 23% at 1 year, which was significantly higher than in renal transplant recipients without TB (AHR, 4.13, 95% CI, 2.21, 7.71, p < 0.001). Although uncommon, MTB infection is associated with a substantially increased risk of mortality after renal transplantation. High-risk groups, particularly those with SLE prior to transplant, might benefit from intensified screening.     

Rumination: One Construct, Many Features in Healthy Individuals, Depressed Individuals, and Individuals with Lupus

Rumination has been associated with depression and negative health effects. Yet measures of rumination appear to index multiple constructs that may be differentially related to clinical phenomena. To clarify this literature, we explored convergence and divergence among self-report measures of rumination in 349 undergraduates, 59 depressed adults, 81 healthy adults, and 15 never-depressed adults with Systemic Lupus Erythematosis (SLE). Results suggested there are separate constructs labeled rumination with different relationships to depression. Yet, aggregate measures index a central construct. Depressed individuals ruminated more, across measures, than individuals with SLE, who ruminated more than healthy individuals; this relationship was mediated by dysphoria. Thus, administering multiple rumination measures and attending to constructs assessed by rumination measures appears important in clinical studies.     

红斑狼疮皮损中CD4^＋和CD8^＋T细胞的表达

目的检测红斑狼疮皮损区T淋巴细胞亚群CD4 和CD8 T细胞的表达情况。方法采用免疫组织化学法对红斑狼疮皮损区淋巴细胞进行检测,并与正常皮肤作对照。结果红斑狼疮患者皮损CD4 T细胞百分数明显高于正常对照组。CD8 T细胞百分数明显低于正常对照组。结论红斑狼疮患者可能存在CD4 T细胞活性增强,CD8 T细胞功能抑制,从而导致免疫紊乱而发病。     

大鼠抗GBM肾炎模型的建立及不同病期的生化指标和肾组织病理学观察

目的：为研究人类新月体抗肾炎的发病机制，建立大鼠抗肾小球基底膜（BGM）肾炎的动物模型，方法：提取S－D大鼠GBM抗原，将此抗原免疫新西兰白兔获得抗血清，再将此抗血清从尾静脉一次性注射给S－D大鼠。实验分2组：肾炎模型组及正常对照组。定期于第4天、第14天第第21天检测大鼠24h尿蛋白，血肌酐及血尿素的含量和肾组织病理学改变。结果：大鼠肾炎模型组：大鼠注射抗血清后于第4天出现大量蛋白尿，第14天血肌酐，血尿素显著升高，并持续上升，肾组织病理表现为肾小球内细胞数明显增加，大量新月体形成及蛋白管型，GBM呈不规则增厚，足突融合，内皮细胞脱落，坏死，免疫荧光检查见IgG、鼠IgG沿GBM线形分布，大鼠正常对照组以上指标均无明显改变。结论：通过动态观察大鼠抗GBM肾炎的病变变化，证实该模型病变与人类新月体性肾炎的病变较为一致，该模型可用于探讨人类新月体体肾炎的实验研究。     

Fiberglass or silica exposure and increased nephritis or ESRD (end-stage renal disease)

The U.S. multiplant cohort mortality study of workers producing manufactured mineral fibers is finding increasing mortality from nephritis and/or nephrosis. We examine other data sets to see if similar effects can be identified. In a case-referent study among Michigan patients with end-stage renal disease (ESRD), men with exposures to silica have elevated odds ratio for ESRD. In a California occupational mortality study based on 1979–81 data, a number of the construction trades, farmers, and farm laborers show excess mortality for renal disease. The highest mortality ratio is found in the category including insulation workers. This ratio remains significantly elevated when adjusted for estimated exposures to smoking, alcohol, and for socio-economic status. California mortality data from 20 years earlier (1959–61) fail to show much excess renal disease in construction workers, but do for farmers. In Singapore, granite workers with a long-term exposure to silica have excess excretion of albumin and similar compounds compared to less exposed controls, leading to the presumption that silica exposure can lead to silica nephrotoxicity. Balkan nephropathy has been associated with consumption of well water high in silica. In the Negev of Israel, dust storms are a vehicle for increasing respiratory uptake of silica. The Beduin, thought to be a population with maximal exposures, have higher rates of ESRD than do Jews in the age groups over 60 years. Although high blood concentrations of silica are found in persons with renal failure, the close association with elevated creatinine has been interpreted as evidence that the buildup of silica is due to renal failure, rather than vice-versa. The evidence is consistent with, but not yet compelling, that exposure to silica, which can be readily absorbed (or dissolved) from the lung, may increase the long-term risk of renal disease including renal failure. © 1993 Wiley-Liss, Inc.     

Lupus vulgaris in a patient with systemic lupus erythematosus and persistent IgG deficiency

We present the case of a patient with juvenile onset systemic lupus erythematosus (SLE) who developed a persistent, acquired hypogammaglobulinaemia with IgG deficiency. The hypogammaglobulinaemia was probably a complication of high dose corticosteroid treatment. The serum IgG level remained subnormal despite intravenous immunoglobulin therapy. Lupus vulgaris, which developed on the nasal cartilage in this patient with SLE, is not an expected finding. This patient is probably the first reported case of SLE associated with lupus vulgaris.     

Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis

Crry (complement receptor 1–related protein/gene y) is a key cellular complement regulator in rodents. It is also present in Fx1A, the renal tubular preparation used to immunize rats to induce active Heymann nephritis (HN), a model of membranous nephropathy. We hypothesized that rats immunized with anti-Fx1A develop autoantibodies (auto-Abs) to Crry as well as to the megalin-containing HN antigenic complex, and that anti-Crry Abs promote the development of injury in HN by neutralizing the complement regulatory activity of Crry. Rats immunized with Fx1A lacking Crry remained free of proteinuria and glomerular deposits of C3 during a 10-wk follow-up despite typical granular immunoglobulin (Ig)G deposits in glomeruli. Anti-Fx1A auto-Abs were present in their sera at levels that were not different from sera pooled from proteinuric rats with HN induced with nephritogenic Fx1A. Passive administration of sheep anti-Crry Abs to rats immunized with Crry-deficient Fx1A led to proteinuria and glomerular C3 deposition, which were not seen in such rats injected with preimmune IgG, nor in rats with collagen-induced arthritis injected with anti-Crry IgG. To directly examine the role of Crry in HN, rats were immunized with Crry-deficient Fx1A reconstituted with rCrry. This led to typical HN, with 8 out of 15 rats developing proteinuria within 14 wk. Moreover, the extent of glomerular C3 deposition correlated with proteinuria, and anti-Crry Abs were present in glomerular eluates. Thus, Crry is a key nephritogenic immunogen in Fx1A. Formation of neutralizing auto-Abs to Crry impairs its function, leading to unrestricted complement activation by Abs reactive with the HN antigenic complex on the epithelial cell surface.     

Characterization of anti-endothelial cell antibodies in systemic lupus erythematosus (SLE).

IgG anti-endothelial antibodies (AEA), as measured by ELISA or immunoblotting technique could be detected in serum samples of 56 out of 64 patients with SLE (88%) and mainly occurred in monomeric form. AEA were not cell specific, because the binding reactivity was absorbed partially by both fibroblasts and peripheral blood mononuclear cells. No correlation was found between the presence of AEA and anti-nuclear antibodies. Immunoblotting revealed reactivity of AEA against endothelial antigens ranging in size from 15 to 200 kD. AEA titres were significantly higher in patients with joint or skin abnormalities, compared with patients without these abnormalities. A significant correlation was found between nephritis in SLE and the presence of AEA reactivity against endothelial membrane antigens of 38, 41 and 150 kD. These data show that the pattern of AEA reactivity in serum of SLE patients is heterogeneous, and suggest that AEA against a limited number of antigens may be involved in the pathogenesis of nephritis in SLE.