Search

Background Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. Methods Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. Results In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. Conclusions The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

Background: Osteonecrosis of the femoral head (ONFH) remains a major cause of disability in patients with systemic lupus erythematosus (SLE) and seriously impairs quality of life. This study aimed to investigate associations between glucocorticoids (GCs), antiphospholipid antibodies (aPLs), and ONFH in patients with SLE. Methods: We conducted a multicentre cohort study on patients with SLE and used a directed acyclic graph-based analysis strategy. Details of GC therapy, aPLs status, other drug administration and other SLE-related characteristics were collected. ONFH occurrence during follow-up was determined by magnetic resonance imaging. Multivariable logistic regression and generalized estimating equation models were performed to assess their effects on ONFH, and a simplified scoring system comprising these factors for short- and medium-term SLE-ONFH prediction was developed by receiver operating characteristic curve analysis. Results: Of 449 SLE patients with a median follow-up duration of 5.3 years, 41 (9.1%) developed ONFH. Independently risk factors of SLE-ONFH including: average daily GC dose with an adjusted odds ratio (aOR) of 1.1 and 95% confidence interval (CI) of 1.0–1.1; GC therapy duration (3–5 years: aOR 3.3, 95% CI 1.4–7.8; >5 years: aOR 8.0, 95% CI 3.3–19.4); initial intravenous GC (aOR 4.4, 95% CI 1.9–10.1); positive aPLs (aOR 2.8, 95% CI 1.4–5.8); and Arterial hypertension secondary to GC usage (aOR 5.2, 95% CI 1.4–19.1). And we successfully developed the simplified scoring system (SCORE model) with an area under the curve of 0.88 (95% CI 0.82–0.94). Conclusion: Based on the risk factors involved in the development of SLE-ONFH, a novel SCORE model was developed, which might be helpful for risk stratification of SLE-ONFH in clinical practice.

Objective To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia. Methods This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid (sUA) levels were ≥480 µmol/l with gout, ≥480 µmol/l without gout but with comorbidities, or ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg, 5 mg, 10 mg of SHR4640, 50 mg of benzbromarone or placebo, respectively. The primary end point was the proportion of subjects who achieved target sUA level of ≤360 µmol/l at week 5. Results 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects who achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in the 5 mg, 10 mg SHR4640 and benzbromarone groups, respectively, significantly higher than the placebo group (0%; P Conclusions The present study indicated a superior sUA-lowering effect and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as compared with placebo in Chinese subjects with hyperuricaemia. Trial registration ClinicalTrials.gov number, NCT03185793

BackgroundAlthough the incidence and clinical manifestations of pituitary apoplexy were reported by a few researches, the results are not consistent. This study aimed to explore the risk factors associated with an incidence of apoplexy in pituitary adenomas.MethodsThe clinical information of 843 patients with pituitary adenoma from the Department of Neurological Surgery, 1st Affiliated Hospital of Kunming Medical University, was reviewed. The incidence, clinical manifestation, and potential risk factors for pituitary apoplexy were analyzed by a case-control study.ResultsIn total, 121 patients (14.4%) with macroadenoma were suffered from pituitary apoplexy. Headache, vomiting, and visual impairment are the top 3 symptoms for the pituitary apoplexy.Logistic regression results showed that the hypertension(hypertension vs non-hypertension OR = 2.765, 95%CI:1.41~5.416), tumor type (negative staining vs. positive staining, OR = 1.501, 95%CI:1.248~5.235), and tumor size (diameter > 2 cm vs. diameter ≤ 2 cm, OR = 3.952, 95%CI:2.211~7.053) are independent factors associated with pituitary apoplexy.ConclusionOur results indicate that the risk factors for the incidence of pituitary apoplexy depend mainly on properties of the tumor itself (tumor size and pathologic type) and the blood pressure of patients.

There is no standard method by which to establish a right one-lung ventilation (OLV) model in rabbits. In the present study, a novel method is proposed to compare with two other methods. After 0.5 h of baseline two-lung ventilation (TLV), 40 rabbits were randomly divided into sham group (TLV for 3 h as a contrast) and three right-OLV groups (right OLV for 3 h with different methods): Deep intubation group, clamp group and blocker group (deeply intubate the self-made bronchial blocker into the left main bronchus, the novel method). These three methods were compared using a number of variables: Circulation by heart rate (HR), mean arterial pressure (MAP); oxygenation by arterial blood gas analysis; airway pressure; lung injury by histopathology; and time, blood loss, success rate of modeling. Following OLV, compared with the sham group, arterial partial pressure of oxygen and arterial hemoglobin oxygen saturation decreased, peak pressure increased and lung injury scores were higher in three OLV groups at 3 h of OLV. All these indexes showed no differences between the three OLV groups. During right-OLV modeling, less time was spent in the blocker group (6±2 min), compared with the other two OLV groups (13±4 min in deep intubation group, P

The objective of the study was to evaluate the efficacy and safety of etanercept (Anbainuo) treatment in Chinese moderate to severe rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX-IR); 600 patients (360 in phase III-1 and 240 in phase III-2) poorly responding to MTX were enrolled in the study and randomized at a ratio of 2:1 into an Anbainuo treatment or control group. The study was designed as a 12-week double-blind, placebo-controlled period followed by a 12-week open-label study. The primary endpoint was the ACR20 response rate at week 12. Secondary endpoints included the ACR50, ACR70, ACR-N, and safety. At week 12, ACR20 response was observed in 60.9 % of the Anbainuo group—significantly higher than that of the control group (20.6 %). At week 24, the ACR20 response in the Anbainuo group increased to 70.2 %; there was no significant difference compared with that of the control group (61.8 %, P > 0.05). At week 12, the ACR50 and ACR70 responses of the Anbainuo group increased to 25.6 and 6.8 %, compared to 4 and 1 % in the control group (P

Background:L-arginine is of great importance in numerous biological procedures in human body, e.g. it participates in the urea cycle for detoxification of ammonia, and functions as a modulator in immune responses (1). Our previous investigation demonstrated that treatment with L-arginine reduced clinical symptoms, bone erosion and osteoclast numbers in serum-induced arthritis (K/BxN) (2). In addition, a decreased concentration of L-arginine has been observed in the serum of rheumatoid arthritis (RA) patients. Altogether, it is suggesting that L-arginine supplementation might be a potential treatment against RA.Objectives:This study aims to investigate the treatment role of L-arginine supplementation in murine arthritis models. The project also plans to delineate the metabolic action of L-arginine supplementation during osteoclast differentiation in the presence of an inflammatory milieu.Methods:Three murine arthritis models (serum-induced arthritis (K/BxN) model, collagen-induced arthritis model and hTNFtg mice model) were applied in the presence or not of oral L-arginine supplementation. MicroCT and histomorphometry analyses were performed to quantify bone erosion and numbers of osteoclasts. In addition, in vitro osteoclastogenesis were performed in the presence of various amounts of L-arginine with or without treatment with 40ng/ml TNFa. OC differentiation was characterized by TRAP staining. Resorption activity was assessed by pit formation assay. Osteoclast markers and metabolic genes were determined with quantitative real-time PCR analysis and western blot. Dihydrorhodamine 123 staining was used to determine the level of intracellular ROS. Seahorse analyses and mass spectrometry metabolites analyses were conducted to address the metabolic condition.Results:Arthritis severities were reduced after L-arginine supplementation in arthritis models. Moreover, an amelioration of bone erosion and reduced osteoclast numbers were observed in arthritic mice treated with L-arginine.In vitrotreatment of L-arginine inhibited osteoclastogenesis, especially in the late phase of the differentiation, even with exposure to TNFa stimulation. The L-arginine induced osteoclast differentiation inhibition is likely due to an alteration in the RANKL/RANK/Traf6 pathway. L-arginine also boosted the intracellular production of ATP and ROS, promoting mitochondria-driven oxidative phosphorylations (OXPHOS), leading to the failure of activation and even death of the osteoclasts.Conclusion:These data strongly suggested that L-Arginine ameliorates bone erosion in RA through the inhibition of RANKL/RANK/Traf6 pathway as well as reprogramming of the cellular metabolism during osteoclastogenesis. The immunometabolism action of L-Arginine might therefore help to reduce joint inflammation and destruction in RA.References:[1] Geiger R, Rieckmann JC, Wolf T, Basso C, Feng Y, Fuhrer T, Kogadeeva M, Picotti P, Meissner F, Mann M, Zamboni N. L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell. 2016 Oct 20;167(3):829-42.[2] Hannemann N, Cao S, Eriksson D, Schnelzer A, Jordan J, Eberhardt M, Schleicher U, Rech J, Ramming A, Uebe S, Ekici A. Transcription factor Fra-1 targets arginase-1 to enhance macrophage-mediated inflammation in arthritis. The Journal of clinical investigation. 2019 May 28;129(7).Disclosure of Interests:Shan Cao: None declared, Xiaoxiang Chen: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Aline Bozec: None declared

Objective To investigate the relation of circulating 25-hydroxyvitamin D (25[OH]D) levels to age, sex, and bone mineral density (BMD) in adults living in Guangzhou Province. Methods This cross-sectional study comprised 188 women and 122 men aged 17–88 years who were randomly sampled among community-dwelling Guangzhou residents. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry, and serum concentrations of 25(OH)D, parathyroid hormone (PTH), procollagen I N-terminal peptide, and beta C-telopeptide of collagen were assayed by electrochemiluminescence immunoassay. Serum 25(OH)D concentrations were divided into four subgroups: severe deficiency (

Aim Patients with rheumatic diseases are at higher risk of developing tuberculosis (TB). The objective of this prospective study was to evaluate the T-SPOT.TB assay (T cell enzyme-linked immuno-spot assay), for the diagnosis of tuberculosis infection in rheumatic disease patients in China. Methods Prospectively enrolled patients came from the Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine between July 2008 and Aug 2012 for TB screening. Subjects' histories of TB infection, previous TB contact or bacille Calmette-Guerin vaccination and concurrent immunosuppressive therapy, were reviewed carefully and recorded in detail. TST (tuberculin skin test) and TSPOT.TB assay were performed on the subjects. A prospective evaluation by Chi-square test was used for sensitivity and specificity of both TST and T-SPOT assay. Results A total of 311 subjects included 114 (36.66%) male and 197 (63.34%) female subjects, with a median age of 37.7 ± 12.6 years (range 17–72). Thirty-two patients (10.29%) had a history of TB infection or previous TB contact; 256 patients (82.32%) were using glucocorticoids or immunosuppressants; 28 patients (9.0%) were clinically diagnosed as having TB infection. The sensitivity and specificity of TST for TB screening in rheumatic disease patients was 81.82% (9/11) and 67% (67/100), respectively. However, the sensitivity and specificity of T-SPOT assay was statistically higher at 92.86% (26/28) and 93.64% (265/283), respectively (P < 0.05). Conclusion As a new immunoassay for TB diagnosis, the sensitivity and specificity of T-SPOT is higher than TST. It is of great importance in the diagnosis of active or latent TB infection in rheumatic disease patients.

Objective Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE) and could be an acute critical condition presenting to the emergency department (ED). Our previous retrospective study revealed that the ED-related mortality of such patients was over 50%. The aim of the current prospective study is to initiate a proactive intense care strategy on severe SLE-PAH patients in the emergency setting and evaluate its impact on the short-term survival. Methods The proactive intense care strategy was applied, which includes: (i) an education and training course on the topic of SLE-PAH for ED physicians; (ii) a SLE-PAH patient triage protocol with prompt specialist consultation and admission; and (iii) intensive care with prompt initiation of combination PAH-targeted therapy, that is, at least two drugs from the three categories as represented by iloprost, bosentan and sildenafil. Consecutive SLE-PAH patients with WHO functional class III or IV who attended the ED were enrolled following the aforementioned protocol. A historical group of SLE-PAH patients in the ED (n = 11) was set up as a comparison, and 3-month short-term survival was calculated. Results During October 2010 to December 2012, a total of 11 consecutive severe SLE-PAH patients were included in the present study. Compared with the historical group, an improved short-term survival can be appreciated over time (historical group vs. proactive group, 27.3% vs. 72.7%, P = 0.033). The application of PAH-targeted combination therapy apparently contributed to the better outcome (P = 0.0099). Conclusions Proactive care and combination PAH-targeted treatment can improve short-term survival of severe SLE-PAH in the emergency setting.

Objective: To test whether inhibition of sclerostin by a targeted monoclonal antibody (Scl-Ab) protects from bone and cartilage damage in inflammatory arthritis. Sclerostin is a potent inhibitor of bone formation and may be responsible for the low level of bone repair in patients with rheumatoid arthritis. Methods: Human tumour necrosis factor transgenic mice (hTNFtg mice) developing inflammatory arthritis and local and bone loss were administered either vehicle, anti-TNF antibody, Scl-Ab, or a combination of both agents. Inflammation, systemic and periarticular bone loss, bone erosion and cartilage damage were evaluated at baseline (week 8) and after 3 weeks of treatment by clinical assessment, micro-CT and histology. Results: Scl-Ab did not affect joint swelling or synovitis. Systemic bone loss in the spine and periarticular bone loss in the proximal tibia were completely blocked and partially reversed by inhibition of sclerostin but not by inhibition of TNF. Moreover, Scl-Ab completely arrested the progression of bone erosion in hTNFtg mice and in combination with TNF inhibition even led to significant regression of cortical bone erosions. Protective effects of Scl-Ab were also observed for the articular cartilage. Conclusions: These data suggest that sclerostin inhibition is a powerful tool to enhance bone repair in inflammatory arthritis.

The impact of metabolic stress induced by obesity on the bone marrow melanoma niche is largely unknown. Here we employed diet induced obese mice model, where mice received high-fat (HFD) or normal diet (ND) for 6 weeks before challenge with B16F10 melanoma cells. Tumor size, bone loss and osteoclasts numbers were assessed histologically in the tibial bones. For defining the molecular pathway, osteopontin knock-out mice, interleukin 6 neutralizing antibody or Janus kinase 2 inhibition were carried out in the same model. Mechanistic studies such as adipocyte-melanoma co-cultures for defining adipocyte induced changes of tumor cell proliferation and expression profiles were also performed. As results, HFD enhanced melanoma burden in bone by increasing tumor area and osteoclast numbers. This process was associated with higher numbers of bone marrow adipocytes expressing IL-6 in direct vicinity to tumor cells. Inhibition of IL-6 or of downstream JAK2 blocked HFD-induced tumor progression. Furthermore, the phenotypic changes of melanoma cells triggered macrophage and osteoclast accumulation accompanied by increased osteopontin expression. Osteopontin triggered osteoclastogenesis and also exerted a positive feedback loop to tumor cells, which was abrogated in its absence. Metabolic stress by HFD promotes melanoma growth in the bone marrow by an increase in bone marrow adipocytes and IL-6-JAK2-osteopontin mediated activation of tumor cells and osteoclast differentiation.

Contents This study is aimed at investigating the developmental potential of the primordial follicles from ovaries of newborn mice after cryopreservation in liquid nitrogen for long-term storage, thawing, and heterografting into the kidney capsules of ovariectomized adult female mice. After stimulation of recipient mice with pregnant mare serum gonadotropin on day-19 after heterografting, the primordial follicles of the transplanted ovaries could develop into antral follicles. When the oocyte-cumulus cell complexes were retrieved from these antral follicles, they could mature after in vitro culture for 16–17 h. After in vitro fertilization, the rates of embryos derived from these oocytes that developed into the two-cell stage and the blastocyst stage after 16–17 h and after day-4, respectively, in the culture medium were 55.40% (55/107) and 9.09% (5/55), respectively. In the ovarian transplantation groups, no pups were derived from the 410 embryos that were transferred into 10 pseudopregnant mothers at the pronuclear stage. However, of the 10 surrogate mothers in whom 570 embryos were transferred at the two-cell stage, four achieved pregnancy and gave birth to 20 live offspring. These results demonstrated that primordial follicles in newborn mice ovaries were capable of sustaining their developmental potential after freezing and thawing. Once transplanted into the kidney capsules of ovariectomized adult female mice, these primordial follicles could develop and respond to gonadotropin stimulation and reach the antral stage; further, live offspring could be derived from these follicles.

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.

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

Objective: To compare the clinical efficacy of concurrent chemoradiotherapy, neoadjuvant chemotherapy, and intracavity brachytherapy in comprehensive treatment for young patients with stage Ib2 cervical cancer. Methods: One hundred and twelve young patients with stage Ib2 cervical cancer were enrolled retrospectively in our hospital from January 2003 to June 2005. They were categorized into three groups according to preoperative regimens, including the concurrent chemoradiotherapy group (Group 1, n=38), the neoadjuvant chemotherapy (Group 2, n=49), and the intracavity brachytherapy group (Group 3, n=25). Radical hysterectomy was performed following these regimens. Chemotherapy and radiotherapy were given according to pelvic lymph node metastasis, deep cervical stromal invasion, intravascular cancer emboli, histological grading, vaginal stump and positive surgical margin. Results: The cancer disappearance and superficial muscle invasion rates were statistically significantly better in the concurrent chemoradiotherapy group than in the other two groups (P

This study aims to evaluate the clinical and radiological efficacy as well as safety profiles of Anbainuo, a recombinant human TNFRII:Fc fusion protein, combined with methotrexate (MTX) versus MTX alone or Anbainuo alone in the treatment of Chinese patients with moderate to severe rheumatoid arthritis (RA). In this 24-week, multicenter, double-blind, active comparator-controlled study, 396 RA patients were randomized into combination therapy group (Anbainuo plus MTX), Anbainuo group, or MTX group. Clinical response was assessed using the American College of Rheumatology (ACR)-N, ACR20, ACR50, ACR70, and van der Heijde modification of Sharp score, among which ACR-N and ACR20 were defined as primary major endpoints. After 24 weeks of treatment, the ACR-N in the combination therapy group (12.79 ± 9.24 %) was significantly higher than that in Anbainuo group (9.56 ± 11.16 %) and in MTX group (5.08 ± 11.1 %) (p = 0.00 and p = 0.00, respectively). Patients in Anbainuo group had significantly higher ACR-N than those in MTX group (p = 0.02). More patients in the combination therapy group (53.6 %) achieved ACR50 improvement response than those in the MTX group (30.8 %). ACR70 of combination therapy group (27.7 %) was significantly higher than that of Anbainuo group (15.8 %) and MTX group (7.70 %), with no significant difference between Anbainuo group and MTX group. DAS28-ESR in the combination therapy group was significantly reduced compared to either monotherapy groups. Moreover, DAS28-ESR was significantly lower in Anbainou group than in MTX group. The combination therapy group also showed significantly less radiographic progression than the MTX group (p = 0.03). The total adverse events (AE) in the combination group (40.9 %) was significantly higher than those in the MTX group (28.8 %) (p < 0.05). Anbainuo combined with MTX therapy can effectively control the disease activity and radiographic progression of RA, while the incidence of AE also increased compared to either Anbainuo or MTX.

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.

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.

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.