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Background Genetic factors link psychiatric disorders, particularly major depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder (OCD), with systemic lupus erythematosus (SLE). Additionally, maternal SLE is a risk factor for long-term developmental problems, particularly learning disabilities, attention disorders, autism spectrum disorder (ASD) and speech disorders, in children. Aim We aimed to determine whether first-degree relatives (FDRs) of patients with SLE have increased risks of SLE and major psychiatric disorders. Design and methods Using the Taiwan National Health Insurance Research Database, we recruited 40 462 FDRs of patients with SLE as well as 161 848 matched controls. The risks of major psychiatric disorders, including schizophrenia, bipolar disorder, OCD, MDD, ASD and attention-deficit/hyperactivity disorder (ADHD), were assessed. Results The FDRs of patients with SLE had higher risks of SLE (reported as the adjusted relative risk and 95% confidence interval: 14.54; 12.19–17.34), MDD (1.23; 1.12–1.34), ADHD (1.60; 1.55–1.65), OCD (1.41; 1.14–1.74) and bipolar disorder (1.18; 1.01–1.38) compared with controls. Specifically, male FDRs of patients with SLE had higher risks of SLE and bipolar disorder, whereas female FDRs of patients with SLE had higher risks of MDD and OCD. Differences in the familial relationship (i.e. parents, children, siblings and twins) were consistently associated with higher risks of these disorders compared with controls. Conclusions The FDRs of patients with SLE had higher risks of SLE, MDD, ADHD, OCD and bipolar disorder than the controls. [ABSTRACT FROM AUTHOR]

Objective The objective of this paper is to investigate the incidence rate, risk factors and outcome of osteomyelitis among patients with systemic lupus erythematosus (SLE). Materials and methods We conducted a cohort study using data for patients enrolled in the Taiwan National Health Insurance Database from 2000 to 2012. Patients with SLE and age- and sex-matched controls without SLE were enrolled. Primary endpoint was the first occurrence of osteomyelitis. Risks of osteomyelitis in SLE patients were analyzed with Cox proportional hazards regression models, including age, sex, comorbidities and medications. Results Among 24,705 SLE patients (88.4% women, mean age 35.8 years) with a median follow-up of 9.1 years, 386 patients had osteomyelitis. The incidence rate ratio (IRR) of osteomyelitis in the SLE group vs the control group was 8.52 (95% confidence interval (CI) 7.24–10.05). The SLE group had higher incidence rates of osteomyelitis than the control group, especially in pediatric subgroups (IRR 41.1 95% CI 18.57–107.35). Compared to controls, SLE patients experienced osteomyelitis at a younger age (42.3 vs 58.1 years) but did not have an increased risk of mortality (hazard ratio 0.7; 95% CI 0.21–2.38). Age >60 years, male gender, malignancy within five years, prior bone fracture and higher daily prednisolone dose (>7.5 mg) cumulatively for >180 days increased risk for osteomyelitis. Conclusions SLE patients have a higher IRR of osteomyelitis than controls. Pediatric and elder SLE patients, patients with a history of bone fracture, malignancy within five years and higher-dose glucocorticoid use have a higher risk of osteomyelitis and should be carefully monitored. [ABSTRACT FROM AUTHOR]

Objective This study investigated whether the incidence of opportunistic infection differed in systemic lupus erythematosus patients who received different doses of corticosteroids. Methods We included patients with diagnosed systemic lupus erythematosus from 1997 to 2010 using Taiwan national health insurance data. The index day for systemic lupus erythematosus patients was 3 months after the systemic lupus erythematosus diagnosis. A non-steroid cohort was matched 4:1 with the steroid cohort according to age, sex and index day. The end of the follow-up period was the day of opportunistic infection diagnosis, 1 year after the index day, or death. Results The overall cumulative incidence of opportunistic infection was 136-fold higher in the steroid cohort than in the non-steroid cohort. The adjusted hazard ratio for developing mycobacterium infection in the steroid cohort was 11, and the adjusted hazard ratio for developing herpes zoster was 43.6 compared to the non-steroid cohort after adjusting for immunosuppressive agents and comorbidities. The adjusted hazard ratio value for opportunistic infection was 1.40 (95% confidence interval (CI) 0.78–2.51) for a daily prednisone-equivalent dose of 7.5–15 mg, 1.72 (95% CI 1.02–2.91) for 15–30 mg, 1.96 (95% CI 1.17–3.28) for 30–60 mg and 2.24 (95% CI 1.26–4.00) for over 60 mg compared with low-dose steroids (<7.5 mg). Conclusion This study confirmed that the risk of opportunistic infection is higher in systemic lupus erythematosus patients treated with steroids in the first 3 months after diagnosis versus those not treated with steroids. Medium and high doses were associated with a higher risk of opportunistic infection compared with low doses. However, there was no controlling for disease activity, making it hard to know if increases in infection were due to disease itself or corticosteroids. [ABSTRACT FROM AUTHOR]

Objective: The objective of this paper is to identify the risk of complications of real-time ultrasound-guided renal biopsy in adult and pediatric patients with systemic lupus erythematosus (SLE). Materials and methods: This retrospective study examined outcomes of 296 renal biopsy procedures in 275 SLE patients. Imaging-confirmed symptomatic hematoma was regarded as a major complication when intervention (blood transfusion, angiographic embolization, or surgery) was required or as a minor complication otherwise. Clinical and laboratory data were compared between groups with or without complications after initial or subsequent renal biopsy. Binary logistic regressions were used to evaluate complication risk of initial renal biopsy. Results: Overall complication rate of initial renal biopsy was 8.7% (major: 2.9%, minor: 5.8%). Three patients expired from pulmonary hemorrhage, thrombotic microangiopathy, and pneumonia. Pediatric SLE patients tended to have a higher rate of major complications (12.5%) than adult patients (2.3%). According to multivariable analysis results, elevated serum creatinine (SCr) level (OR 1.45; 95% CI 1.17-1.81 per mg/dl), prolonged prothrombin time (PT) (OR 2.2; 95% CI 1.05-4.62 per second), and thrombocytopenia (OR 4.3; 95% CI 1.56-11.9) increased overall complication risk of initial renal biopsy. Age < 18 years (OR 8.43; 95% CI 1.21-58.8), thrombocytopenia (OR 16.4; 95% CI 2.44-110.5), and elevated SCr level (OR 1.97; 95% CI 1.36-2.86 per md/dl) increased risk of major complications. Thrombocytopenia, prolonged PT, and elevated SCr level were associated with complications after subsequent renal biopsy (all p = 0.01). Conclusions: SLE patients, particularly patients under 18 years old or with elevated SCr level, prolonged PT, or thrombocytopenia, have an increased risk of complications after initial or subsequent renal biopsy. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) can affect all heart structures including the conduction system, with either reversible or permanent derangement. However, only a few cases of adult SLE and complete atrioventricular (AV) block have been reported. We describe a young pregnant woman who initially presented with complete AV block on electrocardiography before the diagnosis of SLE. Syncope subsequently developed during the postpartum period due to frequent nonsustained polymorphic ventricular tachycardia, suggesting lupus myocarditis. The ventricular arrhythmia was successfully treated by intravenous corticosteroids, lidocaine and implantation of a permanent pacemaker. This may represent the first report of complete AV block with polymorphic ventricular tachycardia, which was identified before the other clinical features of SLE fully manifested. SLE should be considered if a patient presents with complete AV block without other clinical features. It may warn for early diagnosis and appropriate treatment of SLE including lupus-related heart disease. [ABSTRACT FROM AUTHOR]

Objective: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease and usually requires immunosuppressive therapy, which is a major cause of viral reactivation. The incidence and antiviral response in SLE patients with hepatitis C virus (HCV) reactivation is unclear and needs to be investigated. Methods: One hundred and sixty-six SLE patients with antibody to HCV (anti-HCV) status were retrospectively reviewed regarding the events of HCV reactivation. Patients with HCV reactivation were treated with pegylated interferon plus ribavirin treatment. The virological response and relapse rate were evaluated. Results: Twenty-six patients were positive for anti-HCV. During a mean 8.4 years of follow-up, 10 (38.5%) cases developed HCV reactivation. No clear relationship was noted between immunosuppressive therapy and the HCV reactivation. Eight patients underwent antiviral therapy and the rapid virological response (RVR), early virological response, and sustained virological response (SVR) rates were 37.5%, 87.5%, and 75.0%, respectively. However, late relapse (reappearance of HCV RNA in serum after archiving SVR) was found in two (33.3%) of six patients achieving SVR. The two cases were HCV genotype 1 b concurrent with corticosteroid treatment. Conclusions: HCV reactivation in anti-HCV-positive SLE patients was possibly associated with glucocorticoids. The virological response to interferon plus ribavirin treatment is not inferior to the general population. However, monitoring HCV RNA after SVR is necessary for patients concurrent with corticosteroid treatment due to the risk of late relapse. [ABSTRACT FROM AUTHOR]

Foxp3, encoded by the human FOXP3 gene, is a transcription factor that regulates regulatory T-cell (Treg) development and function. Associations have been reported between FOXP3 gene variants and autoimmune endocrinopathy and non-endocrine autoimmune disease. The aim of this study was to investigate the possible influence of single nucleotide polymorphisms (SNP) in the FOXP3 gene on genetic predisposition to systemic lupus erythematosus (SLE). The study cohort comprised 172 SLE patients and 181 controls, who were genotyped for the FOXP3 gene variants. Of five SNPs identified, the FOXP3 -6054 ATT carrier was shown to be associated with renal disorder (odds ratio [OR] 3.26, 95% confidence interval [95% CI] 1.33—8.03, p = 0.0077). Furthermore, lower anti-dsDNA levels were found in patients with the -3279 A carrier (p = 0.0109). To the authors’ knowledge, this is the first study to investigate the association of FOXP3 SNPs with susceptibility to SLE, as well as sub-phenotype susceptibility. Although the exact role of Foxp3 and FOXP3 gene variations in SLE is still not clear, the present data support the importance of variations in the FOXP3 gene region for the etiology of certain manifestations of SLE. [ABSTRACT FROM PUBLISHER]

XRCC1 plays a central role in mammalian DNA repair processes. Two polymorphisms of XRCC1, rs1799782 (Arg>Trp at codon 194) and rs25487 (Arg>Gln at codon 399), are common in the Han Chinese population. Our objective was to analyze the relationship between these two functional single-nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE) in the Taiwanese Han Chinese population. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) on 172 SLE patients and 160 normal controls. Our data indicate that the frequency of A/G at codon 399 differed between patients and controls (p=0.01; odds ratio: 1.80; 95% confidence interval: 1.17-2.75), but the allelic frequency analysis did not reveal significant differences. For the SNP at codon 194, there were no differences in either allelic or genotype frequencies between SLE patients and normal subjects. Clinical association studies of SLE symptoms revealed the involvement of the A/G polymorphism at codon 399 in SLE pathogenesis. Our results indicate that a functional SNP at codon 399 of XRCC1 is associated with the development of SLE. [ABSTRACT FROM AUTHOR]

Tumour necrosis factor-α (TNF-α), an important proinflammatory cytokine, exerts a variety of physiological and pathogenic effects that lead to tissue destruction. Studies on the association of TNF-α genetic polymorphisms with systemic lupus erythematosus (SLE) have yielded inconclusive results. We investigated the association of TNF-α genetic polymorphisms (-1031T/C, -863C/A, -857T/C, -308A/G and +489A/G) with SLE in Taiwanese patients and controls. Our results indicate that 1) the frequency of the A-allele at -863 position was significantly higher in SLE patients (odds ratio = 1.46; 95% CI = 1.02-2.08); 2) the frequency of the A-allele at +489 position was significantly higher in SLE patients (odds ratio = 1.79; 95% CI = 1.21-2.65); 3) the AA or GA genotype frequencies at +489 position were significantly increased in SLE patients (AA genotype: odds ratio = 11.20; 95% CI = 1.36-92.55; GA genotype: odds ratio = 1.63; 95% CI = 1.03-2.58); 4) no significant association of TNF-α haplotypic distributions was observed, except for the haplotypes TCCGA, CACGA and CCCGG; and 5) the genotype frequency of the polymorphisms at -1031 was significantly different in patients with antinuclear antibodies (P = 0.022). The allele and genotype frequencies of the polymorphisms at -863 were not significantly different. The genotype frequency of the polymorphisms at -857 was significantly different in patients with haematological disorder (P = 0.025). The frequency of A allele of the polymorphisms at -308 was significantly increased in patients with malar rash (P = 0.033), discoid rash (P = 0.023), photosensitivity (P = 0.037), oral ulcers (P = 0.002) and serositis (P = 0.029). The genotype frequency of the polymorphisms at +489 was significantly different in patients with discoid rash and photosensitivity (data not shown; discoid rash, P = 0.031; photosensitivity, P = 0.044). These results suggest that TNF-α genetic polymorphisms contribute to SLE susceptibility in the Taiwanese population. [ABSTRACT FROM AUTHOR]

Sunlight/ultraviolet (UV) irradiation has been recognized as an important risk factor for developing systemic lupus erythematosus (SLE). However, the interpretation of genetic variations involved in UV-light sensitivity is largely unknown. Recent studies indicated that two genetic variations of ERCC2/XPD gene (rs1799793 in exon 10 and rs13181 in exon 23) have been found to exert negative influences on nucleotide excision repair system. To analyse the possible contribution of the ERCC2/XPD functional single nucleotide polymorphisms in genetic susceptibility to SLE, the rs13181 and rs1799793 SNPs in ERCC2/XPD were genotyped by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Association was studied by case–control analyses using samples from 172 SLE patients and 160 healthy controls. Haplotype analysis was performed to detect the association with genetic predisposition to SLE and the clinical features. Although these two functional genetic variations are linked to several immune dysfunction-induced diseases, no statistically significant differences in allele or genotype frequencies were observed between SLE patients and controls. Haplotype analysis showed that none of ERCC2/XPD haplotypes was associated with the incidence of SLE disease, nor the preference of clinical features. In conclusion, the ERCC2/XPD functional polymorphisms analysed in this study showed no association in genetic susceptibility to SLE. [ABSTRACT FROM AUTHOR]

Interleukin-18 (IL-18) is associated with chronic inflammation, autoimmune diseases and various cancers and infectious diseases. An IL-18 genetic A/C polymorphism at coding position 105 (rs549908) has been linked with asthma and rheumatoid arthritis. We tested a hypothesis that the IL-18 genetic polymorphism confers systemic lupus erythematosus (SLE) susceptibility. Study participants were Taiwanese SLE patients and a healthy control group. Our results indicate (1) a significantly higher A allele frequency in SLE patients (P = 0.003; OR = 1.97; 95% CI = 1.26-3.08) and (2) a significantly higher A allele frequency in SLE patients with a central nervous system disorder (P = 0.027; OR = 7.18; 95% CI = 0.95-54.28). Our results suggest that the A/C polymorphism contributes to SLE pathogenesis. [ABSTRACT FROM AUTHOR]

Objective. To elucidate the molecular basis of hyporesponsiveness of polymorphonuclear neutrophils (PMN) to interleukin-8 (IL-8) stimulation in patients with active SLE. [ABSTRACT FROM PUBLISHER]

Objective. Identification of the genes responsible for systemic lupus erythematosus (SLE). [ABSTRACT FROM PUBLISHER]

The purpose of this study was to determine if epidermal growth factor receptor (EGFR) gene polymorphism was a marker of susceptibility to or severity of Chinese patients with systemic lupus erythematosus (SLE) in Taiwan. The study included 119 Chinese patients with SLE. One hundred unrelated healthy individuals living in central Taiwan served as control subjects. Polymorphisms of the EGFR Bsr I gene were typed from genomic DNA. The genotypes, allelic frequencies and carriage rates were compared between SLE patients and control subjects. The relationship between allelic frequencies and clinical manifestations of SLE was evaluated. For the genotype of EGFR gene Bsr I polymorphism, there was statistically significant differences between the SLE and control groups (chi-squared test, P ¼ 0.009, x2 ¼ 9.21). In addition, there was significant association between the two groups in allelic frequency of the T allele (P = 0.02, x2 = 5.27). However, we did not detect any association between EGFR genotype and clinical or laboratory profiles in SLE patients. The results suggest that the EGFR gene Bsr I polymorphism is related to SLE. [ABSTRACT FROM AUTHOR]

Summary Decreased number and impaired functions of polymorphonuclear neutrophils (PMN) due to the presence of anti-PMN autoantibodies in the serum render patients with systemic lupus erythematosus (SLE) susceptible to bacterial infections. However, the cognate antigens and pathological mechanisms of anti-PMN autoantibodies in SLE are rarely reported in the literature. In this study, we found approximately 20% of SLE sera contained anti-PMN autoantibodies detected by human PMN-coated cellular ELISA. A membrane protein with molecular weight of 50 kDa was identified as the cognate antigen of anti-PMN in Western blot after membrane-biotinylation and streptavidin column elution. The 50 kDa molecule was proved to be SSB/La after immunoscreening, molecular cloning and nucleotide sequencing of the gene from the human leucocyte cDNA library. Human anti-SSB/La autoantibodies purified from active SLE sera passing through the recombinant SSB/La conjugated Sepharose 4B affinity column could bind and penetrate into normal human PMN. Functional analysis revealed that the anti-SSB/La autoantibodies exerted a number of potent effects on human PMN, including suppressed phagocytosis, accelerated apoptosis and enhanced IL-8 production. These in vitro results suggest that anti-SSB/La is one of the anti-PMN autoantibodies capable of penetrating into PMN and responsible for neutropenia and functional impairment of PMN in patients with SLE. [ABSTRACT FROM AUTHOR]

Affinity-purified human polyclonal anti-double-stranded DNA antibodies (anti-dsDNA) exerted a cytostatic effect towards human and rat glomerular mesangial cells (MC). In order to identify the cognate antigens for anti-dsDNA on the surface of MC, we used these autoantibodies to probe a human renal λg11 cDNA expression library. Two cDNA clones encoding the cognate proteins for the autoantibodies were isolated. Sequencing analysis of the two cDNA showed that they had 98.6% homology with the gene of the P0 and 99.2% homology with the gene of the Pi human acidic ribosomal phosphoproteins (P protein). Two galactosidase fusion proteins (125 000 and 150 000 MW) derived from the two cDNA inserts expressed in lysogenic Escherichia coli Y1089 could react with the original screening antibodies in an immunoblotting analysis. After transformation and expression of the full-length P1 clone in prokaryotic cells, the purified P1 protein was able to react with anti-dsDNA. In a cross-inhibition experiment, the dsDNA binding activity of anti-dsDNA was inhibited by a synthetic polypeptide corresponding to the carboxyl terminal 20 amino acids of P protein and purified P1 protein in a dose-dependent manner, but this was less potent than the inhibition caused by calf thymus dsDNA. By use of well-defined systemic lupus erythematosus (SLE) sera, we found only sera containing a high titre of anti-dsDNA activity (>300 IU/ml) reacted with P1 of rat MC lysate. Furthermore, the 38000 and 19000 MW macromolecules were proved to be the cognate antigens for anti-dsDNA expression on the surface of the MC, by Western blot of the MC plasma membrane lysates. These results suggest that antidsDNA may cross-react with ribosomal P proteins expressed on the surface of the MC and exert cytostasis towards these cells. [ABSTRACT FROM AUTHOR]

Interleukin-1 receptor antagonist (IL-lra) binds competitively to IL-1 receptors but does not transduce the signal which blocks the biological activities induced by IL-1. In this study, polymorphonuclear neutrophils (PMN) and mononuclear cells (MNC from the patients with active systemic lupus erythematosus (SLE) ( = 11), inactive SLE ( = 13) and normal individuals ( = 13) were compared for the IL-lra producing capacity of these cells. PMN and MNC at a concentration of 1 × 10 cells/ml were incubated with medium alone (spontaneous) or stimulated with lipopolysaccharide (LPS, 100 ng/ml) for 24 h. The IL-lra concentration in the supernatants was quantified by ELISA method. Both spontaneous and LPS-stimulated production of IL-lra by PMN, but not by MNC, of active SLE were significantly lower than that of inactive SLE or normal groups. Prednisolone (1 and 5 μg/ml) did not change the production of IL-lra by normal PMN either spontaneously or LPS-stimulation in study. Moreover, the IL-lra producing capacity of PMN in seven active SLE on admission and after intensive immunosupprcssive treatment was measured. These results suggest that the defective IL-lra production by SLE-PMN is relevant to disease activity and may be regarded as a new indicator of disease activity in patients with active SLE. [ABSTRACT FROM PUBLISHER]

Cytidine deaminase activity (CD) in the neutrophil culture supernatants (PMN SUP) of 27 patients with systemic lupus erythematosus (SLE) was measured using a spectrophotometric method. Compared with the controls (5.449±1.358 U/5 × 10 PMN), the CD activity in the spontaneous culture supernatants of PMN was significantly increased in active (10.003±2.637 U/5 × 10 PMN) but not in inactive (5.358±1.624 U/5 × 10 PMN) SLE. However, after stimulation with -formyl-methionyl-leucyl-phenylalanine (FMLP, 1 × 10 M), the ratio of enzyme activity between stimulated and spontaneous PMN supernatants was decreased in active SLE (0.794±0.178) compared with normal controls (1.300±0.225). In contrast, the enzyme activity in the cytoplasm of either stimulated or non-stimulated PMN was not different among these three groups. These results suggest that CD of PMN is releasable and can be enhanced by chemotactic factor stimulation in normal PMN. The increased spontaneous release of CD by active SLE PMN is one of the indicators for the disease activity in these patients. [ABSTRACT FROM PUBLISHER]