Search

Aim: To examine the effects of a novel immunosuppressant, FTY720, on BXSB lupus-prone mice, and to investigate its immune regulatory pathway by using a cDNA microarray. Methods: Male BXSB mice received oral administration of 10 mg/kg FTY720 twice a week from age 9 weeks. Levels of antinuclear antibodies in serum and histopathology of the kidney were evaluated. The gene expression profile of splenic lymphocyte was analysed by cDNA microarray. Results: FTY720 suppressed the production of antinuclear antibodies (P

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) can modulate immune responses, but whether it directly affects B cell function is unknown. Patients with systemic lupus erythematosus, especially those with antinuclear Abs and increased disease activity, had decreased 1,25(OH)2D3 levels, suggesting that vitamin D might play a role in regulating autoantibody production. To address this, we examined the effects of 1,25(OH)2D3 on B cell responses and found that it inhibited the ongoing proliferation of activated B cells and induced their apoptosis, whereas initial cell division was unimpeded. The generation of plasma cells and postswitch memory B cells was significantly inhibited by 1,25(OH)2D3, although the up-regulation of genetic programs involved in B cell differentiation was only modestly affected. B cells expressed mRNAs for proteins involved in vitamin D activity, including 1α-hydroxylase, 24-hydroxylase, and the vitamin D receptor, each of which was regulated by 1,25(OH)2D3 and/or activation. Importantly, 1,25(OH)2D3 up-regulated the expression of p27, but not of p18 and p21, which may be important in regulating the proliferation of activated B cells and their subsequent differentiation. These results indicate that 1,25(OH)2D3 may play an important role in the maintenance of B cell homeostasis and that the correction of vitamin D deficiency may be useful in the treatment of B cell-mediated autoimmune disorders.

The combined presence of anti-phospholipid Ab (aPL), thrombosis, and/or fetal loss is recognized as the antiphospholipid syndrome (APS). aPL include anti-cardiolipin Ab (aCL) and/or lupus anticoagulants (LAC, detected as Ig that prolong certain in vitro phospholipid (PL)-restricted blood clotting tests); both aCL and LAC are the diagnostic Ab for APS. Studies show that aPL represent a heterogeneous group of Ab, which recognize various PL, PL-binding plasma proteins, and/or PL-protein complexes. Recently, we found that five of seven patient-derived IgG monoclonal aCL react with thrombin, activated protein C, and plasmin. All three proteins are trypsin-like serine proteases (SP), and are highly homologous in their catalytic domains. Importantly, among these SP autoantigens, the reactive aCL bind to plasmin with the highest affinity, suggesting that plasmin may serve as a major driving autoantigen for some aCL in ∼30% of APS patients who are positive for IgG anti-plasmin Ab. To test this hypothesis, we immunized BALB/c mice with human plasmin and analyzed immune sera for aCL activity and reactivity with relevant SP. We found that some immune sera displayed aCL activity and/or bound to test SP. Subsequently, eight mAb were obtained and studied. The results revealed that one mAb displayed the aCL and the LAC activities and induced fetal loss when injected into pregnant mice. Immunohistological analyses of placentas revealed extensive deposits of activated C3 components. Combined, these data demonstrate that plasmin may serve as a driving Ag for some pathogenic aPL.

Aim: To investigate the long-term prognosis of systemic lupus erythematosus (SLE) and its risk factors. Methods: An 18-year (1980–1998) clustering follow-up study of 50 patients with SLE was performed. Results: The overall survival rate at 1, 5, 10, 15 and 18 years after the onset of illness was 98%, 98%, 84%, 76%, and 70%, respectively. The two major causes of death were infection and renal failure. Cox proportional hazard regression analysis showed that the presence of ≥ 7 of the American College of Rheumatology criteria for SLE at diagnosis and vasculitis were associated with worse survival. Thirteen (26%) patients were in remission with complete discontinuation of drugs, with the mean remission duration being 12 years (range: 2–17 years). Conclusion: It is possible for patients with SLE to get long-term remission through timely and effective treatment. Prevention of infection and renal failure and reducing dosage of corticosteroids by combined treatment with immunosuppressive drugs may enhance prognosis and survival in SLE.

Objective: To evaluate the differences in the renal survival of lupus nephritis (LN) diagnosed either during 1985–1994 or 1995–2004 and to analyse the possible causes. Methods: Fifty-two patients with biopsy-confirmed LN were followed up between 1985 and 1994 and 130 patients were followed up between 1995 and 2004. Renal survival was studied with Kaplan-Meier analysis and the log rank test. Status at diagnosis and treatment schedules were also analysed. Results: Renal survival was significantly better in the patients who were diagnosed between 1995 and 2004 (P = 0.0233). The mean time from initiation until first diagnosis of SLE, from the initiation of SLE until referral to our centre, and from first detection of proteinuria until kidney biopsy was significantly shorter in the later decade (P

A community-based survey on the prevalence of knee osteoarthritis (OA) and associated factors was carried out in Shanghai, People's Republic of China.Of 2,305 registered residentsor=40 years of age, 2,093 were examined by interview and questionnaire. One hundred ninety knee pain-positive and 510 knee pain-negative subjects received radiography.Radiographic knee OA (RKOA) was found in 72.1% (137/190) of symptomatic and 41.6% (212/510) of asymptomatic subjects (SKOA and AsKOA, respectively). The estimated prevalences of symptomatic and asymptomatic knee OA in the community were 7.2% and 37.4%, respectively. Women had higher SKOA prevalence than men (9.8% vs 3.7%, P0.01). Compared with Caucasians, the urban Shanghai population had a higher prevalence of tibiofemoral joint OA.There was a higher proportion of SKOA than AsKOA (72.1% vs 41.6%), and SKOA was significantly more associated with disability (81.0% vs 26.9%, P0.01). The prevalence of SKOA increased with age, from 1.3% in the 40-49-year-old age group to 13.2% in the 70+ group. Age, body mass index, and female gender were associated risk factors for knee OA.

Systemic sclerosis (SSc) is a progressive fibrotic disorder with no legitimate effective treatment. Several clinical trials had investigated imatinib mesylate with a target dose of 400∼600 mg/day on SSc, and the efficacy is controversial with a generally poor tolerability. We herein reported six female Chinese patients with SSc administered with low-dose imatinib (200 mg/day) for a median of 23 months (10∼30 months). Patients displayed a decreased modified Rodman skin scores (mRSS) by a mean of 6.29 points after 6 months of treatment. Three patients who completed 2 years of treatment achieved a reduction of mRSS by 8, 18, and 30.5 points, respectively. Pulmonary function was improved or stabilized in two patients with interstitial lung disease. Severe gastrointestinal involvement in one patient was attenuated in terms of discontinuation of total parenteral nutrition and restoration of the serum albumin level. Imatinib was well-tolerated in general, although there were two severe adverse events: a bone fracture and a cerebral hemorrhage in two individuals. Both the adverse events were probably not directly related to imatinib and were recovered uneventfully. Our limited data, along with the review of the literature, suggested that low-dose imatinib might be effective and better tolerated in severe SSc that deserves further study.

Lupus myelopathy (LM) is a rare but critical condition, and the prognosis is grim for patients with severe initial motor deficits despite aggressive conventional immunosuppressive therapy. In this report, six recent-onset severe LM patients with lower extremity muscle strength less than or equal to grade 3 were treated with rituximab combined with pulse methylprednisolone. Four patients showed complete myelopathy response at 12 months. The safety profile of rituximab was tolerable, with urinary tract infection as the most frequent adverse event. Preliminary data indicated that rituximab could be beneficial in preventing permanent neurological damage in severe LM.

Background Neuropsychiatric systemic lupus erythematosus (NPSLE) is a major complication for lupus patients, which often leads to cognitive disturbances and memory loss and contributes to a significant patient morbidity and mortality. The presence of anti-neuronal autoantibodies (aAbs) has been identified; as examples, anti-NMDA receptors and anti-Ribsomal P aAbs have been linked to certain pathophysiological features of NPSLE. Methods and Findings In the current study, we used a proteomic approach to identify an intermediate neurofilament alpha-internexin (INA) as a pathogenetically relevant autoantigen in NPSLE. The significance of this finding was then validated in an expanded of a cohort of NPSLE patients (n = 67) and controls (n = 270) by demonstrating that high titers of anti-INA aAb was found in both the serum and cerebrospinal fluid (CSF) of ∼50% NPSLE. Subsequently, a murine model was developed by INA immunization that resulted in pronounced cognitive dysfunction that mimicked features of NPSLE. Histopathology in affected animals displayed cortical and hippocampal neuron apoptosis. In vitro studies further demonstrated that anti-INA Ab mediated neuronal damage via inhibiting axonal elongation and eventually driving the cells to apoptosis. Conclusions Taken together, this study identified a novel anti-neurofilament aAb in NPSLE, and established a hitherto undescribed mechanism of aAb-mediated neuron damage that could have relevance to the pathophysiology of NPSLE.

To evaluate the prevalence of atherosclerosis in Chinese premenopausal women with systemic lupus erythematosus (SLE) and study possible associations between traditional and nontraditional risk factors with premature atherosclerosis.We evaluated 111 premenopausal women with SLE and 40 healthy controls without clinical cardiovascular disease. B-mode ultrasound was used to measure carotid plaque and intima-media wall thickness (IMT). The frequency of risk factors for atherosclerosis in patients and controls was compared, and the relationship between the patients' clinical characteristics and carotid plaque was examined. At the same time, we used B-mode ultrasound to measure flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the brachial artery to assess for difference in endothelial function between SLE patients and controls.Carotid plaque was more frequent in patients with lupus (16 of 111 patients) than in control subjects (0 of 40 subjects) (P = 0.007). The mean IMT was significantly higher in patients than in controls. Compared with controls, SLE patients were found to have a significantly higher prevalence of hypertension (P = 0.001), hypercholesterolemia (P = 0.022), and hypertriglyceridemia (P0.001). As compared with patients without plaque, patients with plaque were significantly older, had longer disease duration, higher body mass index, raised blood pressure, shorter prothrombin time, raised C-reactive protein, higher Systemic Lupus International Collaborating Clinics damage index score, higher cumulative prednisone dose, used less hydroxychloroquine, had higher mean IMT, lower FMD, and NMD. In logistic regression analysis, older age, higher body mass index, and higher Systemic Lupus International Collaborating Clinics damage index score were independently related to the presence of plaque. Using multiple regression analysis, we found SLE (P = 0.003) to be significantly associated with impaired FMD.In our Chinese SLE group, patients presented a higher prevalence of carotid atherosclerosis plaque than healthy controls. SLE patients have significant endothelial dysfunction. We found that risk factors identified in other SLE populations were associated with atherosclerosis in our Chinese group.

Several studies by microarray analysis and real-time polymerase chain reaction (RT-PCR) reveal that type I interferon-inducible genes (IFIGs) are implicated in systemic lupus erythematosus (SLE). To find a potential clinical biomarker capable of monitoring lupus disease activity clinically, quantitative RT-PCR was used to identify transcript expression levels of 13 type I IFIGs in peripheral blood cells in 144 patients with SLE, 27 non-SLE patients and 60 healthy controls and then analyse connections between gene expression and disease activity. The expression levels of five type I IFIGs (LY6E, OAS3, IFIT4, OAS1 and OAS2) were significantly higher in the SLE group than in the healthy and non-SLE controls. LY6E gene that had highest expression was chosen to analyse the association of expression level with clinical features. Compared to low LY6E expression group, SLE patients with high LY6E expression had higher SLEDAI-2K score, increased 24 h urine protein and lower blood C3 complement. Active SLE patients had more elevated LY6E expression than stable patients. And LY6E expression levels in patients with SLE were strongly correlated with their SLEDAI-2K scores. Our results indicate that increased expression of LY6E gene in peripheral blood cells in patients with SLE is correlated with lupus activity and may be a useful, noninvasive biomarker for assessing SLE disease activity.

Glycogen storage diseases (GSDs) are a group of congenital inherited metabolic diseases. They may present the symptoms of muscle and joint which may be misdiagnosed with some rheumatic diseases. We report three cases of GSDs in order to have a more clear recognition of the disease and to discuss the differential diagnosis.

The aim of the study was to investigate the characteristics of adult clinically amyopathic dermatomyositis (CADM) with rapid progressive interstitial lung disease (ILD). Hospitalized patients with dermatomyositis (DM) and polymyositis (PM) between 1998 and 2005 in the Shanghai Renji Hospital were retrospectively studied. One hundred and forty-five patients were classified into CADM, classic DM or PM according to the modified Sontheimer's definition or Bohan-Peter's classification criteria. They were further stratified based on the presence or absence of clinical ILD. The Kaplan-Meier survival analysis and COX regression were performed. The predictive factors for ILD and other clinical properties of CADM-ILD were explored. The presence of clinical ILD was a significant risk factor for the poor outcome of DM/PM (OR = 4.237, CI 95%: 1.239-14.49, p = 0.021). Other risk factors are the presence of rashes and elevated urea nitrogen. Patients with DM/PM complicated by ILD had different clinical courses. Patients with CADM-ILD showed a rapidly progressive pattern with 6-month survival rate of 40.8%. The DM-ILD manifested a progressive pattern with a 5-year survival rate of 54%, while PM-ILD was chronic with 5- and 10-year survival rate of 72.4% and 60.3%, respectively. Better preserved muscle strength, elevated erythrocyte sedimentation rate, and hypoalbuminemia may herald ILD in DM/PM. Patients with CADM-ILD who later died had lower PO(2), higher lactate dehydrogenase, and prominent arthritis/arthralgia compared with those who survived. The presence of antinuclear antibody seems to be protective. Rapid progressive CADM-ILD is refractory to conventional treatment. ILD is a common complication in over 40% of our hospitalized DM/PM cohort and is also a prominent prognostic indicator. CADM is a special phenotype of DM/PM. CADM-ILD, which is usually rapidly progressive and fatal, requires further investigation.

The purpose of this study is to describe the etiology, characteristics and outcomes of central nervous system (CNS) infections in patients with systemic lupus erythematosus (SLE), while also identifying prognostic and risk factors. Thirty-eight SLE patients with CNS infections were identified from review of all charts of patients with SLE hospitalized from January 1995 to June 2005. These patients were divided into 3 groups, i.e., Mycobacterium tuberculosis (TB), non-TB bacterial and fungal infection groups. Of the 38 SLE cases with CNS infections, TB was identified in 19 patients, Listeria monocytogenes in 3 patients, Klebsiella pneumoniae in 1 patient, Staphylococcus aureus in 1 patient, Gram's stain positive bacteria in 1 patient, Cryptococcus neoformans in 12 patients, and Aspergillus fumigatus in 1 patient. The rate of unfavorable outcome in patients with fungal infection was lower than in patients with TB (P=0.028) and non-TB bacterial CNS infections (P=0.046). SLE patients with TB or fungal CNS infections had a more insidious or atypical clinical presentation. Compared to SLE patients without CNS infections, those with CNS infections were more likely to have low serum albumin levels (P=0.048) and have been receiving higher doses of prednisolone at the onset of CNS infection (P=0.015) or higher mean doses of prednisolone within the previous year (P=0.039). In conclusion, low levels of serum albumin and higher doses of received prednisolone are important risk factors for the development of CNS infections in SLE patients.

Takayasu’s arteritis (TA) is a vasculitis characterized by inflammation and obliteration of intermediate to large-size arteries. We report a case of Takayasu’s arteritis with a presentation of bilateral pulmonary nodular infiltrates in a 21-year-old man. An open-lung biopsy showed characteristic changes of extra-vascular granulomatosis. To our knowledge, this has not been described previously in the literature.

A prospective echocardiographic and clinical study was performed on 84 Chinese patients with systemic lupus erythematosus (SLE) and 99 controls to investigate the prevalence and the mechanism of pulmonary hypertension (PH) in SLE. Comparison between Doppler estimation and catheterization measurement was made in 12 cases to validate the predictive method. Compared to normal subjects, lupus patients had significantly increased systolic pulmonary artery pressure (SPAP) (29.59 +/- 12.52 vs 19.64 +/- 5.82, P0.001), mean pulmonary artery pressure (MPAP) (15.11 +/- 7.36 vs 10.21 +/- 4.72, P0.001) and total pulmonary resistance (TPR) (315.85 +/- 190.65 vs 220.37 +/- 55.92, P0.001). Nine of the 84 patients presented PH, defined as SPAP30 mmHg and MPAP20 mmHg. Pulmonary hypertensive patients had higher serum endothelin (ET) than non-pulmonary hypertensive patients, were more commonly in active stages, and presented Raynaud's phenomenon and rheumatoid factors. ET level was correlated with echocardiographic pulmonary pressure. Pulmonary hypertension commonly occurs in Chinese patients with SLE (11%), and it correlates with the lupus activity and the elevation of serum endothelin.

To test the hypothesis that rheumatoid arthritis in patients in China is milder in severity than that in patients in a western country, a comparison was made of 2 series of consecutive outpatients with definite or classic rheumatoid arthritis who were attending referral centers in Melbourne, Australia and Shanghai, China. This paper reports the findings on radiographs of the wrists and hands. Making allowances for age and duration of disease, changes were more frequent and severe in the Australian patient series, particularly at the meta-carpophalangeal joints.

A comparison was made of two series of consecutive outpatients with a presumptive diagnosis of rheumatoid arthritis (RA) attending referral centres in Melbourne and Shanghai. No significant differences were observed in disease onset, course, presence of antinuclear antibodies (ANA), or seropositivity. In the Australian series there was a higher frequency of nodules, Raynaud's phenomenon, carpal tunnel syndrome, and 'classical' in comparison with 'definite' disease, and a lower frequency of lymphadenopathy and hepatomegaly. Joint tenderness and soft tissue swelling tended to be more marked in the Chinese series, while deformity and limited range of movement were less severe. Drug therapy was similar overall but influenced by drug availability. Peptic ulceration was recorded in 28% of the Australian series but in only 6% of the Chinese; although 25% of the Chinese were receiving antacids and 6% antiulcerants. X-rays of hands and feet showed more severe disease in the Australian series. The older age group and longer duration of the disease in the Australian patients, who had more chronic and less active disease, may have influenced some of these results.