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Background: Anti-Ro-52 antibodies have been associated with interstitial lung disease (ILD) in various autoimmune diseases. However, their role in ILD among patients with idiopathic inflammatory myopathies (IIMs) is relatively underexplored. This study aimed to investigate the association between anti-Ro-52 antibodies and the occurrence of ILD in individuals with IIMs., Methods: This retrospective observational study included 604 patients who underwent myositis autoantibody testing between July 2018 and January 2021 at our hospital and were diagnosed with either IIMs or IIM-mimics. Comparative analyses were conducted between IIMs and IIM-mimics, as well as within the IIM group between cases with and without ILD. Logistic regression or Firth's logistic regression analyses were employed to assess the risk of ILD development in different IIM subgroups and myositis antibody categories., Results: This study included 190 patients with IIM and 414 patients with IIM-mimics. Patients with IIM demonstrated higher incidence of ILD, concurrent autoimmune disease, and a greater likelihood of various myositis autoantibodies when compared to the IIM-mimics group. Within the IIM patient cohort, those with ILD exhibited a later age of onset of IIM, an increased mortality rate, and a more frequent presence of anti-aminoacyl-tRNA synthetase (ARS) antibodies compared to those without ILD. The presence of any myositis-specific antibody (MSA) was associated with a six-fold increased risk of ILD, while dual positivity for MSA and anti-Ro-52 antibodies conferred a twenty-fold risk. Anti-ARS antibodies carried a 14-fold increased risk of ILD, which escalated to 38-fold in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies. Anti-Ro-52 antibodies alone increased the risk eight-fold., Conclusions: Among patients with IIM, the presence of ILD was linked to higher mortality. Certain autoantibodies, notably anti-ARS and anti-Ro-52 antibodies, were associated with an increased risk of ILD. The greatest risk of ILD was observed in cases of dual positivity for anti-ARS and anti-Ro-52 antibodies., (© 2024. The Author(s).)

Systemic lupus erythematosus (SLE) is an autoimmune disease with various clinical presentations. Mucin deposition is a characteristic finding in skin lesions, but it is rare in other organs. We present a case with erythematous patches from the terminal ileum to the anus in an SLE patient. Diffuse colitis was diagnosed clinically. However, in addition to inflammatory cell infiltration, there was abundant mucinous material deposition in the submucosa. The mucinous material was positive for Alcian blue staining (pH 2.5) and was sensitive to hyaluronidase digestion. These findings are similar to those of cutaneous mucinosis in SLE patients. This is thought to be the first case of gastrointestinal tract mucinosis in SLE reported in the literature., Competing Interests: Declaration of Conflict InterestsThe author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The mutual exclusivity of myositis-specific antibodies (MSAs) has been reported before, but the coexistence of 2 or more MSAs was still found in a few case reports. This study aims to confirm the existence and prevalence of double MSAs in patients with idiopathic inflammatory myopathy (IIM) and to clarify the clinical features of these patients. One hundred fifty-one patients with IIM diagnosed from 1 July 2018 to 31 July 2022, at National Cheng Kung University Hospital, Taiwan, were enrolled and divided into two groups, patients with ≤1 MSA ( n = 128, 84.8%) and those with ≥2 MSAs ( n = 23, 15.2%) according to the initial serology results. After being re-examined by ANA-IIF assay, 8 out of 23 patients were confirmed to have ≥2 MSAs. The demographic data and clinical features were presented. The prevalence of double-positive MSAs among IIM was 5.3% in this cohort. The coexistence of two MSAs in an IIM patient does exist but is rare. Patients with two MSAs belonging to two distinct IIM subtypes presented clinical features skewed to one subtype instead of "mixed phenotypes". No apparent difference in clinical severity was found between patients with ≥2 MSAs and ≤1 MSA. Longer follow-ups and more studies are required to characterize the patients of IIM with ≥2 MSAs., Competing Interests: The authors declare no conflict of interest.

Objective: Children of women with systemic lupus erythematosus (SLE) are at risk for childhood-onset SLE (cSLE). This study evaluated the incidence of early-onset cSLE and associated risk factors, including concomitant maternal and paternal autoimmune diseases, for these children., Methods: A population-based cohort study was conducted using national databases including the linked information of children and parents. Children of women with SLE and those of women without SLE were identified between 2004 and 2015. The cumulative cSLE incidence was estimated using the Kaplan-Meier method. The marginal Cox model was used to calculate the hazard ratio (HR) for cSLE events., Results: A total of 4,419 singletons of women with SLE and 1,996,759 singletons of women without SLE were identified. There were 9 (0.20%) and 503 (0.03%) incident cases of early-onset cSLE for offspring of women with and without SLE, respectively (incidence rate ratio, 8.34; 95% confidence interval [CI], 3.79-15.95]. The adjusted HR of incident cSLE in children of women with SLE was 4.65 (95% CI 2.11-10.24). Other risks for cSLE included pregnancy-induced hypertension/preeclampsia/eclampsia, paternal SLE, paternal Sjögren's syndrome (SS), and maternal SS., Conclusions: This national child-parent cohort study demonstrated that children of women with SLE are at significantly higher risk for cSLE during early childhood. Moreover, paternal SLE and parental SS increase the risk of cSLE for offspring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Chen, Lin, Weng, Kuo and Shieh.)

Background/purpose: The estimated prevalence of xerostomia (lack of saliva) ranges from 10% to 50% of the general population. The oral cavity provides a multivariant environmental habitat to over 700 species of bacteria and fungi. We hypothesized that xerostomia will alter the composition of oral microbiota., Material and Methods: Nineteen xerostomia patients and 10 healthy normal volunteers were studied for the oral microbiota. Gingival plaques were collected and microbiota were detected using bacterial 16S ribosomal RNA and analyzed based on the levels of phylum and class., Results: In all cases, phyla of Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria make up to 100% of oral microbiota at phylum level. Analyzing individual phylum, presence of Bacteroidetes in xerostomia patients and normal subjects were 23.12 ± 2.56% and 23.23 ± 2.58%, respectively. Mean percentage presence of Firmicutes phylum in xerostomia patients and normal subjects were 18.94 ± 1.83% and 14.06 ± 0.98%, respectively. Statistically significant difference was not observed between xerostomia patients and normal subjects in this study., Conclusion: These observations revealed obvious but not statistically significant changes in oral major microorganism phylum between xerostomia patients and normal subjects in this study. More samples are needed to verify the current results and to use oral microbiota as a tool in the diagnosis of xerostomia., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2021 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Background : Pulmonary arterial hypertension (PAH) is a life-threatening disease with different etiologies and outcomes. We aimed to explore differences in clinical features and outcomes of idiopathic PAH (iPAH) and connective tissue disease-related PAH (CTD-PAH) in Taiwanese patients and determine risk factors for mortality. Methods : We retrospectively reviewed the medical records of patients with right-sided heart catheterization-diagnosed PAH between January 2005 and December 2015. The iPAH ( n = 31) and CTD-PAH ( n = 14) patients were enrolled and followed until December 31, 2019. Between-group comparisons were conducted. Potential predictors of the mortality of PAH were determined using the Cox proportional hazard regression model. Results : CTD-PAH patients had higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and lower predicted diffusing capacity of carbon monoxide (DLCO) than iPAH patients. The mortality rates were similar between CTD-PAH and iPAH (21.4% vs. 22.6%, p = 0.99). A mean pulmonary arterial pressure (mPAP) > 46 mmHg was a predictor of PAH-induced mortality (adjusted hazard ratio 21.8, 95% confidence interval 2.32-204.8). Conclusions : A higher mPAP level, but not underlying CTDs, imposed a significantly increased risk of mortality to patients with PAH.

Accumulated evidence suggests a pathogenic role of reactive oxygen species (ROS) in perpetually rheumatoid joints. Therefore, the application of radical scavengers for reducing the accumulation of ROS is beneficial for patients with rheumatoid arthritis (RA). We synthesized water-soluble fullerenols that could inhibit the production of ROS and applied intra-articular (i.a.) injection in an experimental arthritis model to examine the anti-arthritic effect of the synthesized compound. RAW 264.7 cells were used to examine the activity of the synthesized fullerenol. Collagen-induced arthritis (CIA) was induced in Sprague-Dawley rats by injecting their joints with fullerenol. The therapeutic effects were evaluated using the articular index as well as radiological and histological scores. Dose-dependent suppression of nitric oxide (NO) production caused by the fullerenol was demonstrated in the RAW 264.7 cell culture, thus confirming the ability of fullerenol to reduce ROS production. In the fullerenol-injected joints, articular indexes, synovial expression of ROS, histological and radiological scores, pannus formation, and erosion of cartilage and bone were all reduced. Moreover, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) levels were reduced, and fewer von Willebrand factor (vWF)-stained areas were identified in the fullerenol-treated joints than in control joints. The i.a. injection of fullerenol for reducing ROS production can ameliorate arthritis in joints by suppressing pro-inflammatory cytokine production and the angiogenesis process. Thus, the i.a. injection of fullerenol for reducing the production of ROS can be used as a pharmacological approach for RA patients.

Background: No population-based study has investigated the cumulative incidence of pulmonary arterial hypertension (PAH) in patients with newly diagnosed systemic lupus erythematosus (SLE) or the survival impact of PAH in this population., Method: We used a nationwide database in Taiwan and enrolled incident SLE patients between January 1, 2000, and December 31, 2013. The cumulative incidence of PAH in the SLE patients and the survival of these patients were estimated by the Kaplan-Meier method. Potential predictors of the development of PAH were determined using a Cox proportional hazards regression model., Results: Of 15,783 SLE patients, 336 (2.13%) developed PAH. The average interval from SLE diagnosis to PAH diagnosis was 3.66 years (standard deviation [SD] 3.36, range 0.1 to 13.0 years). Seventy percent of the patients developed PAH within 5 years after SLE onset. The 3- and 5-year cumulative incidence of PAH were 1.2% and 1.8%, respectively. Systemic hypertension was an independent predictor of PAH occurrence among the SLE patients (adjusted hazard ratio 2.27, 95% confidence interval 1.59-2.97). The 1-, 3-, and 5-year survival rates of SLE patients following the diagnosis of PAH were 87.7%, 76.8%, and 70.1%, respectively., Conclusions: PAH is a rare complication of SLE and the majority of PAH cases occur within the first 5 years following SLE diagnosis. Systemic hypertension may be a risk factor for PAH development in the SLE population. The overall 5-year survival rate after PAH diagnosis was 70.1%.

Objective: Despite aggressive therapeutic regimens, diffuse alveolar haemorrhage (DAH) is still associated with a high mortality rate in systemic lupus erythematosus (SLE). This study was carried out in patients with SLE-associated DAH with a focus on their therapeutic modality., Method: A retrospective review was performed in 839 Han Chinese lupus patients hospitalized for their DAH manifestation from May 2006 to December 2016., Results: There were 24 episodes in 17 cases (2.0% incidence), 15 females and two males aged 19-67 years (mean ± sd 38.2 ± 15.1 years). High disease activity [Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) 12-31, 19.8 ± 5.6] was found at the onset of DAH. All patients were treated with high-dose corticosteroid, followed by pulse methylprednisolone (70.6%), plasmapheresis (41.2%), pulse cyclophosphamide (35.3%), and rituximab (23.5%). Six patients (35.3%), including three with extracorporeal membrane oxygenation, died owing to acute respiratory failure. All patients receiving rituximab treatment survived with a follow-up period of 12-58 months (40.8 ± 21.1 months), and no further relapse was noted in three cases with a history of recurrent DAH episodes. In addition, there was a significant decrease in their lupus activity (SLEDAI-2K 21.5 ± 6.0 to 6.3 ± 1.7, p = 0.0286)., Conclusion: In this single-centre series with SLE-associated DAH in Han Chinese patients, a beneficial effect of rituximab therapy was observed.

Objective: We analyzed the clinical observations of target arterial infusion of verapamil combined with chemotherapy as therapy for advanced gastric cancer., Patients and Methods: From March 2012 to December 2015, a total of 63 patients with advanced gastric cancer were admitted to our department. The target artery in the control group was perfused with chemotherapy drugs only, and the target artery in the therapy group was injected with verapamil combined with chemotherapy drugs., Results: The therapeutic effect of the therapy group was significantly better than that of the control group in the primary foci of gastric cancer. Liver metastatic lesions: 11 patients in the control group had liver metastases and 25 patients in the therapy group had liver metastases. The effective rate (CR+PR) of the therapy group was significantly better than the control group. Clinical benefit evaluation: in the therapy group of 43 cases, 40 cases presented positive clinical benefit and 38 cases positive clinical weight in KFS scoring system; the clinical benefit of the therapy group was significantly better than control group. Survival analysis: the disease progression-free rate and survival rate of the therapy group were 12 months and 24 months, which were higher than those in the control group. The median PFS and median OS were also significantly longer than those in the control group (p<0.01). In the therapy group, adverse effects of chemotherapy in 43 patients were relieved in a short time., Conclusions: Target arterial infusion of verapamil combined with chemotherapy drugs for advanced gastric cancer can significantly improve the efficacy of chemotherapy drugs and prolong the survival of patients.

Despite a high prevalence of ankylosing spondylitis (AS) in Han Chinese, the clinical experience remains very limited in the extra-articular presentation of inflammatory bowel disease (IBD). A monocentric retrospective study was performed for the AS-associated IBD manifestation. This study analyzed AS patients fulfilling the 1984 revised New York diagnostic criteria, excluding those who had the onset of IBD before or concurrently with the diagnosis of AS, for their demographic, clinical, laboratory, radiological, pathological and medication data, particularly in the usage of anti-TNF monoclonal antibody. Among 988 AS patients with 19.8% female, 4 (0.4%) had the overt IBD presentation, one female and 3 male aged 28 to 47 years (38.8 ± 4.6), all ulcerative colitis with the characteristic histopathological findings. At the onset of colitis, all had a long-term disease duration of 10 to 25 years (17.5 ± 6.5) and high BASDAI 7.5 to 8.8 (8.2 ± 0.5) with the hip joint involvement. There were recurrent flares of colitis despite the treatment with corticosteroids and messalazopyrin/salazopyrin, and no relapses of IBD were observed for 6.0 ± 1.1 years after the adalimumab (ADA) therapy. In this retrospective cohort, we demonstrate the rarity of AS-associated IBD manifestation in Han Chinese with a beneficent effect from the ADA therapy.

Background: Gastrointestinal microbiota, particularly gut microbiota, is associated with human health. The biodiversity of gut microbiota is affected by ethnicities and environmental factors such as dietary habits or medicine intake, and three enterotypes of the human gut microbiome were announced in 2011. These enterotypes are not significantly correlated with gender, age, or body weight but are influenced by long-term dietary habits. However, to date, only two enterotypes (predominantly consisting of Bacteroides and Prevotella) have shown these characteristics in previous research; the third enterotype remains ambiguous. Understanding the enterotypes can improve the knowledge of the relationship between microbiota and human health., Results: We obtained 181 human fecal samples from adults in Taiwan. Microbiota compositions were analyzed using next-generation sequencing (NGS) technology, which is a culture-independent method of constructing microbial community profiles by sequencing 16S ribosomal DNA (rDNA). In these samples, 17,675,898 sequencing reads were sequenced, and on average, 215 operational taxonomic units (OTUs) were identified for each sample. In this study, the major bacteria in the enterotypes identified from the fecal samples were Bacteroides, Prevotella, and Enterobacteriaceae, and their correlation with dietary habits was confirmed. A microbial interaction network in the gut was observed on the basis of the amount of short-chain fatty acids, pH value of the intestine, and composition of the bacterial community (enterotypes). Finally, a decision tree was derived to provide a predictive model for the three enterotypes. The accuracies of this model in training and independent testing sets were 97.2 and 84.0%, respectively., Conclusions: We used NGS technology to characterize the microbiota and constructed a predictive model. The most significant finding was that Enterobacteriaceae, the predominant subtype, could be a new subtype of enterotypes in the Asian population.

Objective: To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment., Design: National prospective cohort study., Setting: 15 medical centres in different regions of Taiwan, from July 2009 to August 2014., Participants: 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants' peripheral blood was used to assess the presence of HLA-B*58:01., Main Outcome Measures: Incidence of allopurinol induced SCARs with and without screening., Results: Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test)., Conclusions: Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres., (© Ko et al 2015.)

Eighty-one stool samples from Taiwanese were collected for analysis of the association between the gut flora and obesity. The supervised analysis showed that the most, abundant genera of bacteria in normal samples (from people with a body mass index (BMI) ≤ 24) were Bacteroides (27.7%), Prevotella (19.4%), Escherichia (12%), Phascolarctobacterium (3.9%), and Eubacterium (3.5%). The most abundant genera of bacteria in case samples (with a BMI ≥ 27) were Bacteroides (29%), Prevotella (21%), Escherichia (7.4%), Megamonas (5.1%), and Phascolarctobacterium (3.8%). A principal coordinate analysis (PCoA) demonstrated that normal samples were clustered more compactly than case samples. An unsupervised analysis demonstrated that bacterial communities in the gut were clustered into two main groups: N-like and OB-like groups. Remarkably, most normal samples (78%) were clustered in the N-like group, and most case samples (81%) were clustered in the OB-like group (Fisher's P  value = 1.61E - 07). The results showed that bacterial communities in the gut were highly associated with obesity. This is the first study in Taiwan to investigate the association between human gut flora and obesity, and the results provide new insights into the correlation of bacteria with the rising trend in obesity.

Background: Opportunistic infection has been documented in systemic lupus erythematosus with special attention paid to Pneumocystis jirovecii because of the significant morbidity and high mortality., Objectives: The limited large-scale investigations covering P. jirovecii pneumonia (PCP) in systemic lupus erythematosus following biologics or immunosuppressants therapy prompted us to perform this study in southern Taiwan., Methods: A retrospective study was completed in 858 hospitalized lupus patients from January 2000 to December 2011. The definite diagnosis of PCP was made by the laboratory detection of Pneumocystis organisms together with consistent clinical and radiological manifestations of PCP. Positive polymerase chain reaction results of sputum samples were not regarded as infection in this study, unless P. jirovecii was the sole pathogen found and pulmonary manifestations resolved following antibiotics for PCP treatment alone., Results: The laboratory identification of Pneumocystis organisms depended on lung biopsy in 2 cases and bronchoalveolar lavage in 3 patients. Five cases, 2 women and 3 men aged 30 to 50 years (41.8 ± 8.8 years), were identified with a 0.6% incidence. None received chemoprophylactics against P. jirovecii infection. All had lupus nephritis and lymphopenia with low CD4 T-cell counts. Prior usages of higher daily prednisolone dosages and concomitant biologics or immunosuppressants were observed in all patients. Pneumocystis jirovecii pneumonia contributed to a high mortality rate (60%)., Conclusions: We report the rare occurrence but high mortality of PCP infection in this study. A consensus guideline addressing prophylactic antibiotics against Pneumocystis organisms in highest-risk lupus patients on biologics or immunosuppressants could be helpful in guiding their management.

Recently, single nucleotide polymorphisms (SNPs) located in specific loci or genes have been identified associated with susceptibility to colorectal cancer (CRC) in Genome-Wide Association Studies (GWAS). However, in different ethnicities and regions, the genetic variations and the environmental factors can widely vary. Therefore, here we propose a post-GWAS analysis method to investigate the CRC susceptibility SNPs in Taiwan by conducting a replication analysis and bioinformatics analysis. One hundred and forty-four significant SNPs from published GWAS results were collected by a literature survey, and two hundred and eighteen CRC samples and 385 normal samples were collected for post-GWAS analysis. Finally, twenty-six significant SNPs were identified and reported as associated with susceptibility to colorectal cancer, other cancers, obesity, and celiac disease in a previous GWAS study. Functional analysis results of 26 SNPs indicate that most biological processes identified are involved in regulating immune responses and apoptosis. In addition, an efficient prediction model was constructed by applying Jackknife feature selection and ANOVA testing. As compared to another risk prediction model of CRC for European Caucasians population, which performs 0.616 of AUC by using 54 SNPs, the proposed model shows good performance in predicting CRC risk within the Taiwanese population, i.e., 0.724 AUC by using 16 SNPs. We believe that the proposed risk prediction model is highly promising for predicting CRC risk within the Taiwanese population. In addition, the functional analysis results could be helpful to explore the potential associated regulatory mechanisms that may be involved in CRC development., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Novel peripheral nerve conduits containing the negatively charged Tremella fuciformis polysaccharide (TF) were prepared, and their efficacy in bridging a critical nerve gap was evaluated. The conduits were made of poly(D,L-lactide) (PLA) with asymmetric microporous structure. TF was immobilized on the lumen surface of the nerve conduits after open air plasma activation. The TF-modified surface was characterized by the attenuated total reflection Fourier-transformed infrared spectroscopy and the scanning electron microscopy. TF modification was found to enhance the neurotrophic gene expression of C6 glioma cells in vitro. TF-modified PLA nerve conduits were tested for their ability to bridge a 15 mm gap of rat sciatic nerve. Nerve regeneration was monitored by the magnetic resonance imaging. Results showed that TF immobilization promoted the nerve connection in 6 weeks. The functional recovery in animals receiving TF-immobilized conduits was greater than in those receiving the bare conduits during an 8-month period. The degree of functional recovery reached ~90% after 8 months in the group of TF-immobilized conduits.

Since large-scale reports of pulmonary infarction in systemic lupus erythematosus (SLE) are limited, a retrospective study was performed for this manifestation in 773 hospitalized patients in southern Taiwan from 1999 to 2009. Pulmonary infarction was defined as the presence of pulmonary embolism, persistent pulmonary infiltrates, and characteristic clinical symptoms. Demographic, clinical, laboratory, and radiological images data were analyzed. There were 12 patients with pulmonary embolism and 9 of them had antiphospholipid syndrome (APS). Six patients (19 to 53 years, average 38.2 ± 12.6) with 9 episodes of lung infarction were identified. All cases were APS and four episodes had coincidental venous thromboembolism. There were four episodes of bilateral infarction and seven episodes of larger central pulmonary artery embolism. Heparin therapy was routinely prescribed and thrombolytic agents were added in two episodes. Successful recovery was noted in all patients. In conclusion, there was a 0.8% incidence of pulmonary infarction in patients with SLE, all with the risk factor of APS. Differentiation between pulmonary infarction and pneumonia in lupus patients should be made; they have similar chest radiography with lung consolidation but require a different clinical approach in management. Although this report is a retrospective study with relatively small numbers of lupus patients with lung infarcts, our observation might provide beneficial information on the clinical features and radiological presentations during the disease evolution of pulmonary infarction in SLE with APS.

Indoleamine 2,3-dioxygenase (IDO) has been known as an emerging therapeutic target in autoimmunity-related arthritis. The treatment responses of adenoviral vectors encoding IDO (AdIDO) gene therapy in rat collagen-induced arthritis (CIA) were examined in this study. The therapeutic effects on ankle circumference, articular index, and radiographic and histological scores were evaluated in AdIDO-injected ankle joints. We further determined CD4+ T-cell numbers and their apoptotic status, CD68(+) macrophage numbers, kynurenine (a downstream tryptophan metabolite) concentrations, interleukin-17 (IL-17) levels, and retinoic acid-related orphan receptor γt (RORγt) expression in synovial tissues of CIA rats receiving AdIDO treatment. Reduction of ankle circumference, articular index, and radiographic and histological scores were noted in AdIDO-treated ankles, as compared with those receiving injection of control vectors. Furthermore, IDO gene transfer led to decreased infiltrating CD4+ T cells with enhanced apoptosis, reduced CD68+ macrophage numbers, increased kynurenine levels, lower IL-17 concentrations, and decreased RORγt expression within the ankle joints. In addition, such a therapy diminished type II collagen-specific IL-17 production and RORγt expression in CD4+ T cells from draining lymph nodes of CIA rats. Our results demonstrate for the first time that intra-articular delivery of IDO gene ameliorated ankle arthritis of CIA rats by induction of CD4+ T-cell apoptosis and reduction of synovial IL-17 production through the supplement of kynurenine. Taken together, these findings implicate the novel strategy of using IDO gene as a therapeutic approach in treating patients with rheumatoid arthritis.

As very few large scale publications of invasive fungal infection (IFI) have been reported in lupus patients from individual medical centers, a retrospective study was performed from 1988 to 2009 in southern Taiwan. Demographic characteristics, clinical and laboratory data, and mycological examinations were analyzed. Twenty cases with IFI were identified in 2397 patients (0.83% incidence). There were 19 females and one male with an average age of 31.8 +/- 12.6. Involved sites included eight disseminated cases, six central nervous system, four lungs, one abdomen and one soft tissue. IFI contributed to a high mortality with 10 deaths (50%), and there were no survivors for the disseminated cases and Candida-infected patients. High activity (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) > 8) was noted in 50% of IFI episodes. The survival from IFI diagnosis to death was only 7.7 +/- 4.2 days, all in a rapid course. No statistical difference was found between survivors and non-survivors when comparing their SLEDAI. Eighty-five percent of IFI episodes under high dosages of corticosteroids therapy and 95% of patients had lupus nephritis. There was an increased risk of IFI in the lupus patients receiving high daily dosage of prednisolone therapy. Critical information from analyses of the present large series could be applied into clinical practices to reduce the morbidity and mortality in such patients.

Mycophenolate mofetil (MMF) has recently been introduced as an immunosuppressive agent for the treatment of glomerulonephritis with systemic lupus erythematosus (SLE) and the data have been encouraging. However, response to MMF treatment appears to differ ethnically. Therefore, we determined efficacy and safety of low-dose MMF for Taiwanese patients with lupus nephritis. We studied 36 lupus nephritis patients who were treated with MMF. The dose started at 0.5 g/day and we collected the data from patients who received up to 1 g/day MMF. Outcome measures were 24 h for proteinuria, serum creatinine, C3/C4 levels, and anti-dsDNA titers collected at the baseline and at 3-month treatment intervals. Daily urinary protein significantly decreased from 6.15 +/- 4.28 g to 2.69 +/- 2.36 g at the last visit (P < 0.01) in spite of the significant absence of changes in serum creatinine levels. The response rate was 65.7% including five (14.3%) cases of complete remission and 18 (51.4%) cases of partial remission. The concomitant oral prednisolone dose decreased significantly from 20.07 +/- 11.78 mg/day to 13.93 +/- 6.79 mg/day at 6 months (P < 0.01). The level of C3 increased significantly from 59.46 +/- 32.73 to 71.99 +/- 25.81 (P < 0.01) and the anti-dsDNA antibody titer decreased from 161.71 +/- 221.42 to 46.57 +/- 117.47 (P < 0.01). No severe adverse effects were observed in the study. Low-dose MMF (0.5 to 1 g/day) combined with glucocorticoids appears to be a safe and effective therapy for lupus nephritis in Taiwanese patients. Our results suggest that lupus nephritis in Oriental patients might respond to lower doses of MMF than Caucasians.

Objectives: To analyse the characteristic features of patients with coexistence of gouty arthritis and pyarthrosis at our university hospital in southern Taiwan, an area with high prevalence of hyperuricemia and gout., Methods: A retrospective chart review was performed for patients who had concomitant gouty and septic arthritis from July 1998 to June 2008. Clinical and laboratory data of these patients were analysed. Furthermore, a comparison was made with published cases in English literature., Results: Fourteen cases with coexistence of gouty arthritis and pyarthrosis have been identified during the past 10 years. There were 13 male and 1 female, all of Han Chinese in ethnicity, with ages ranging from 45 to 85 and an average of 63.7 years. At disease presentation, there were 11 oligoarticular cases (78.6%), 2 monoarticular cases (14.3%) and 1 polyarticular case (7.1%). Ankle and knee joints were most commonly involved. Bacteriological analyses demonstrated gram-positive cocci in 12 cases, of these 10 were oxacillin-sensitive Staphylococcus aureus (71.4%). Multiple tophi deposition was noted in 13 patients (92.9%) and among them 11 patients (84.6%) had associated chronic kidney disease., Conclusion: Different clinical presentations and bacteriological characteristics have been identified in the present series. While the mechanisms responsible for such a coexistence remain to be elucidated, these cases underline the importance of thorough evaluation of the aspirated synovial fluid. Our report adds a novel insight into the understanding of the clinical and microbiological manifestations of such a rare concurrence of gouty and septic arthritis.

Programmed death-1 (PD-1) was shown to deliver an inhibitory signal after binding to its ligands, PD-L1 (B7-H1) or PD-L2 (B7-DC). Recently, up-regulated expression of PD-1 molecule and/or its ligands was demonstrated in human diseases including rheumatoid arthritis and inflammatory colitis. The study aimed to investigate the expression and function of PD-1 and PD-1 ligands on circulating T cells, B cells and monocytes from patient with systemic lupus erythematosus (SLE). The results showed that patients with SLE had significantly increased percentages of PD-1-expressing CD3+T cells and CD19+B cells, PD-L1-expressing CD19+B cells and PD-L2-expressing CD14+B monocytes. In selected SLE patients and normal subjects, functional study of PD-1/ PD-1 ligands pathway on the production of cytokines by stimulated PBMC was examined. Blockages of PD-1 or PD-1 ligands substantially increased the production of IL-2, IFN-gamma and IL-10, the amplitude of increase roughly ranged from one to three times. There were no significant differences of the enhancing effects on cytokine production by blockage of PD-1/PDL pathway between SLE patients and normal subjects. The study indicates that there are no intrinsically defective expression and function of PD-1 and PD-1 ligands on PBMC in patients with SLE.

Objectives: It is well known that small cell carcinoma (SmCC) arising at extrapulmonary sites leads to a poor prognosis for patients. Owing to the infrequency of primary SmCC of the head and neck, it is very unlikely that any large, controlled study will ever be performed. For this reason, recommendations for the treatment of SmCC arising in the head and neck are based primarily on retrospective data from various small case series., Patients and Methods: We report five patients with SmCC of the head and neck seen between 2001 and 2007. In two patients, the SmCCs are in the larynx; in another two patients, in the sinonasal region; and in one patient, in the tonsil., Results: Four patients accepted concurrent chemoradiation therapy (CCRT). Their outcomes are as follows: two patients died, one has adrenal and bone metastasis but is still alive, and one shows no evidence of disease after treatment. One patient refused CCRT and died within 6 months., Conclusions: The prognosis for patients with primary SmCC of the head and neck is generally poor. Treatment most often involves a combination of radiotherapy and chemotherapy, and hope for improved outcomes hinges principally on the development of improved chemotherapies and other systemic treatments.

CD4+CD25+bright T cells played a crucial role in the suppression of immune response. Recently, decreased levels of CD4+CD25+bright T cells in the peripheral blood of patients with systemic lupus erythematosus were reported, suggesting the potential role of CD4+CD25+bright T cells in human autoimmune diseases. Primary Sjögren's syndrome (pSS) is another common human systemic autoimmune disease. The present study aimed to investigate the levels of CD4+CD25+bright T cells in pSS and to correlate their levels with some biomarkers of inflammation and immune activation. Thirty-three patients with pSS and 35 age- and sex-matched normal individuals were enrolled in the study. The flowcytometric method was applied in the measurement of CD4+CD25+bright T cells. The results showed that patients with pSS had statistically lower levels of CD4+CD25+bright T cells than normal controls, expressed either as absolute cell numbers (mean+/-SD: 47.07+/-25.53 cells/mm3 versus 79.55+/-34.56 cells/mm3, P<0.001) or as percentages of peripheral blood mononuclear cells (mean+/-SD: 2.79+/-1.06% versus 3.84+/-1.42%, P<0.001) or as percentages of CD4+ T cells (mean+/-SD: 7.85+/-2.62% versus 11.68+/-3.78%, P<0.005). Moreover, there were statistically significant inverse correlations between the levels of CD4+CD25+bright T cells and some parameters of inflammation or immune activation including erythrocyte sedimentation rate, C-reactive protein, IgG and rheumatoid factors. The result suggested that CD4+CD25+bright T cells were likely to play anti-inflammatory and immunosuppressive roles in the pathogenesis of pSS. However, the exact functions of decreased circulating CD4+CD25+bright T cells in pSS need further elucidated.