We performed a nationwide study to determine the distributions of the signs and clinical markers of systemic lupus erythematosus (SLE) and identify any patterns in their distributions to allow ...patient subclassification. We obtained 256,999 patient-year records describing the disease status of SLE patients from 2003 to 2010. Of these, 14,779 involved patients diagnosed within the last year, and 242,220 involved patients being followed up. Along with basic descriptive statistics, we analyzed the effects of sex, age and disease duration on the frequencies of signs in the first year and follow-up years. The patients and major signs were clustered using the Ward method. The female patients were younger at onset. Renal involvement and discoid eczema were more frequent in males, whereas arthritis, photosensitivity and cytopenia were less. Autoantibody production and malar rash were positively associated with young age, and serositis and arthritis were negatively associated. Photosensitivity was positively associated with a long disease duration, and autoantibody production, serositis and cytopenia were negatively associated. The SLE patients were clustered into subgroups, as were the major signs. We identified differences in SLE clinical features according to sex, age and disease duration. Subgroups of SLE patients and the major signs of SLE exist.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
On-line preconcentration system for the selective, sensitive and simultaneous determination of chromium species was investigated. Dual mini-columns containing chelating resin were utilized for the ...speciation and preconcentration of Cr(III) and Cr(VI) in water samples. In this system, Cr(III) was collected on first column packed with iminodiacetate resin. Cr(VI) in the effluent from the first column was reduced to Cr(III), which was collected on the second column packed with iminodiacetate resin. Hydroxyammonium chloride was examined as a potential reducing agent for Cr(VI) to Cr(III).
The effects of pH, sample flow rate, column length, and interfering ions on the recoveries of Cr(III) were carefully studied. Five millilitres of a sample solution was introduced into the system. The collected species were then sequentially washed by 1
M ammonium acetate, eluted by 2
M nitric acid and measured by ICP-AES. The detection limit for Cr(III) and Cr(VI) was 0.08 and 0.15
μg
l
−1, respectively. The total analysis time was about 9.4
min.
The developed method was successfully applied to the speciation of chromium in river, tap water and wastewater samples with satisfied results.
In vitro display methods are superior tools for obtaining monoclonal antibodies. Although totally in vitro display methods, such as ribosome display and mRNA display, have the advantages of larger ...library sizes and quicker selection procedures compared with phage display, their applications have been limited to single-chain Fvs due to the requirement for linking of the mRNA and the nascent protein on the ribosome. Here we describe a different type of totally in vitro method, DNA display, that is applicable to heterodimeric Fab fragments: in vitro compartmentalization in water-in-oil emulsions allows the linking of an oligomeric protein and its encoding DNA with multiple ORFs. Since previously used emulsions impaired the synthesis of functional Fab fragments, we modified conditions for preparing emulsions, and identified conditions under which it was possible to enrich Fab fragments 106-fold per three rounds of affinity selection. Furthermore, we confirmed that genes encoding stable Fab fragments could be selected from a Fab fragment library with a randomized hydrophobic core in the constant region by applying heat treatment as a selection pressure. Since this method has all advantages of both phage display and totally in vitro display, it represents a new option for many applications using display methods.
Invariant natural killer T (iNKT) cells play a protective role in the development
of certain autoimmune diseases. However, their precise role in the pathogenesis
of autoimmune arthritis remains ...unclear. In this study, we examined the possible
contribution of iNKT cells in collagen-induced arthritis (CIA) by using iNKT cell-deficient
mice (Jα281−/− mice). CIA in these mice was markedly suppressed and interleukin
(IL)-17 production was reduced in a native type II collagen (CII)-specific T cell
response. Draining lymph nodes of CII-immunized Jα281−/− mice contained a significantly
low number of IL-17-producing T helper cells. To determine whether iNKT cells
produce IL-17, we measured IL-17 by enzyme-linked immunosorbent assay in iNKT
cells stimulated with the ligand, α-galactosylceramide (α-GalCer). Notably, splenocytes
from Jα281−/− mice stimulated in this way were negative for IL-17, whereas those
from C57BL/6 mice produced IL-17. Immunostaining for IL-17 in iNKT cells confirmed
intracellular staining of the protein. RT-PCR analysis showed that iNKT cells
expressed retinoid-related orphan receptor γT and IL-23 receptor. Moreover, cell
sorting demonstrated that NK1.1− iNKT cells were the main producers of IL-17 compared
with NK1.1+ iNKT cells. IL-17 production by iNKT cells was induced by IL-23-dependent
and -independent pathways, since iNKT produced IL-17 when stimulated with either
IL-23 or α-GalCer alone. Our findings indicate that iNKT cells are producers and
activators of IL-17 via IL-23- dependent and -independent pathways, suggesting
that they are key cells in the pathogenesis of CIA through IL-17.
Summary
Programmed cell death‐1 (PD‐1) plays an important role in peripheral T cell tolerance, but whether or not it affects the differentiation of helper T cell subsets remains elusive. Here we ...describe the importance of PD‐1 in the control of T helper type 1 (Th1) cell activation and development of forkhead box protein 3 (FoxP3+) regulatory T cells (Tregs). PD‐1‐deficient T cell‐specific T‐bet transgenic (P/T) mice showed growth retardation, and the majority died within 10 weeks. P/T mice showed T‐bet over‐expression, increased interferon (IFN)‐γ production by CD4+ T cells and significantly low FoxP3+ Treg cell percentage. P/T mice developed systemic inflammation, which was probably induced by augmented Th1 response and low FoxP3+ Treg count. The study identified a unique, previously undescribed role for PD‐1 in Th1 and Treg differentiation, with potential implication in the development of Th1 cell‐targeted therapy.
Summary
The tumour necrosis factor (TNF)‐α‐induced proteins (TNFAIP)9 and TNFAIP3 play an important pathogenic role in murine arthritis. To clarify their pathophysiological roles in patients with ...rheumatoid arthritis (RA), we examined their expression and localization in peripheral blood mononuclear cells (PBMC). TNFAIP9 and TNFAIP3 mRNA expression was determined in PBMC of RA patients and healthy subjects (control). Flow cytometry was used to analyse the main TNFAIP9‐ and TNFAIP3‐expressing cell populations. TNFAIP9 and TNFAIP3 mRNA expression levels were examined in vitro on CD14+ cells stimulated with TNF‐α and lipopolysaccharide (LPS). The expression levels of TNFAIP9 and TNFAIP3 mRNA were also measured before and 12 weeks after treatment with tocilizumab and abatacept. TNFAIP9 expression was significantly higher, while TNFAIP3 expression was lower in PBMC of RA (n = 36) than the control (n = 24) (each P < 0·05). TNFAIP9 was expressed on CD14+ cells, especially in human leucocyte antigen D‐related (HLA‐DR)+CD14brightCD16−cells, while TNFAIP3 was expressed mainly on CD3+ T cells. TNF‐α and LPS induced TNFAIP9 and TNFAIP3 in human CD14+monocytes in vitro. Treatment with tocilizumab (n = 13), but not abatacept (n = 11), significantly reduced TNFAIP9 mRNA expression in PBMC, which was associated with reduction in the number of circulating CD14bright monocytes. The expression of TNFAIP9 in CD14+ cells was specifically elevated in patients with RA, regulated by TNF‐α and LPS, and suppressed by tocilizumab, while TNFAIP3 in PBMC showed different localization and induction patterns.
It is important to assess the mandibular morphology when orthognathic surgery, especially mandibular ramus osteotomy, is performed. Several studies on three-dimensional (3D) facial asymmetry have ...reported differences in linear and angle measurements between the deviated and contralateral sides in asymmetric mandibles. However, methods used in these studies cannot analyse the 3D morphology of the ramus. In this study, we aimed to evaluate the differences in mandibular ramus between the deviated and contralateral sides in asymmetric mandibles using traditional measurements as well as 3D shape analysis.
15 Japanese females with jaw deformities treated by orthodontic surgery were enrolled. 3D CT images were reconstructed, and 14 landmarks were identified on the model surface. Ten linear and four angle measurements were calculated using these landmarks. Homologous ramus models were constructed for each sample, and after converting all homologous models to the right side, 30 homologous models of the ramus were analysed using principal component analysis.
Firstly, eight principal components explained >80% of the total variance. Differences between the deviated and contralateral sides in measurements and scores of the eight principal components were tested. Significant difference at the 5% level between the deviated and contralateral sides was observed in five linear measurements, three angle measurements and the third principal component. The variance of the deviated side was significantly larger in the diameter between the mandibular notch and coronoid process, horizontal dilated angle of the mandibular ramus and vertical dilated angle of the mandibular ramus. The variance of the contralateral side was significantly larger in the height of mandibular ramus, height of posterior of mandibular ramus, condylar width, height of condylar head and mandibular angle. The squared multiple correlation coefficient adjusted for the degrees of freedom was 0.815. The third principal component showed the difference between the deviated and contralateral sides. Shape variation represented by the third principal component visually indicated that the contralateral side was larger and had inwardly directed coronoid process and the deviated side had a mandibular angle that was turned inwards to a greater extent.
In conclusion, we successfully created a homologous model of the mandibular ramus and demonstrated the effectiveness of this model in the 3D comparison of the ramus morphology between the contralateral and deviated sides in asymmetric mandibles.
Objective: To determine whether occurrence, characteristics, and progression of systemic lupus erythematosus (SLE) are associated with polymorphism of the mannose binding lectin (MBL) gene and with ...serum MBL concentration. Methods: Codon 54 MBL gene polymorphism of 147 patients with SLE and 160 healthy controls was determined by polymerase chain reaction-restriction fragment length polymorphism. Serum concentration of MBL was measured by enzyme immunoassay. Fluctuations of serum MBL were analysed with respect to disease characteristics and activity. Results: Frequency of homozygosity for codon 54 minority allele was 6% (9/147) in patients with SLE, and significantly higher than in controls (p = 0.0294, Fisher’s exact test). MBL polymorphism in patients with SLE was not significantly associated with disease characteristics or immunological phenotypes. Patients homozygous for the B allele tended to have a higher risk of infection during treatment. Levels of C3 and CH50 were slightly, but significantly, associated with serum MBL concentration in patients with SLE homozygous for the majority allele. During the course of SLE, serum MBL concentration increased in 6/14 patients, and decreased in 7 after initiation of immunosuppressive treatment. Conclusions: MBL gene polymorphism influences susceptibility to SLE, but has no direct effect on disease characteristics. Serum MBL levels fluctuate during the course of SLE in individual patients. MBL genotyping may be useful in assessing the risk of infection during treatment of SLE.
Summary
To identify and characterize anti‐citrullinated glucose‐6‐phosphate isomerase (GPI) peptide antibodies in patients with rheumatoid arthritis (RA). Nine GPI arginine‐bearing peptides in human ...GPI protein were selected and cyclic citrullinated GPI peptides (CCG‐1–9) were constructed. Samples were obtained from RA (n = 208), systemic lupus erythematosus (SLE) (n = 101), Sjögren's syndrome (SS; n = 101) and healthy controls (n = 174). Antibodies against CCG‐1–9 were measured, and anti‐citrullinated α‐enolase‐1 (CEP‐1), ‐cyclic citrullinated peptides (CCP) and ‐GPI proteins antibodies were also examined. Patients with RA were genotyped for HLA‐DRB1. The numbers of shared epitope (SE) alleles were counted and compared with those of the autoantibodies. Rabbit GPI was citrullinated with rabbit peptidylarginine deiminase and immunoblot analysis of RA sera performed. The levels of autoantibodies were compared before and after treatment with TNF antagonists in 58 RA patients. Anti‐CCG‐2, ‐4 and ‐7 antibodies were detected in 25·5, 33·2 and 37·0% patients with RA, respectively, and these antibodies were very specific for RA (specificity, 98·1–99·7%). Altogether, 44·2, 86·1 and 13·9% of RA sera were positive for anti‐CEP‐1, ‐CCP and ‐GPI protein antibodies, respectively. Anti‐CCG‐2, ‐4 and ‐7 antibodies were correlated with anti‐CCP and anti‐CEP‐1 antibodies and with the presence of HLA‐DRB1 SE alleles. Citrullinated GPI protein was detected using RA sera. Treatment with tumour necrosis factor antagonists reduced significantly the levels of anti‐CCG‐2 and ‐7 but not of anti‐CEP‐1 antibodies. This is the first report documenting the presence of anti‐CCG antibodies in RA. Anti‐CCG‐2 and ‐7 antibodies could be considered as markers for the diagnosis of RA and its disease activity.
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