MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor.

Regulatory T (Treg) cells are important in maintaining self-tolerance and immune homeostasis. The Treg cell transcription factor Foxp3 works in concert with other co-regulatory molecules, including Eos, to determine the transcriptional signature and characteristic suppressive phenotype of Treg cells. Here, we report that the inflammatory cytokine interleukin-6 (IL-6) actively repressed Eos expression through microRNA-17 (miR-17). miR-17 expression increased in Treg cells in the presence of IL-6, and its expression negatively correlated with that of Eos. Treg cell suppressive activity was diminished upon overexpression of miR-17 in vitro and in vivo, which was mitigated upon co-expression of an Eos mutant lacking miR-17 target sites. Also, RNAi of miR-17 resulted in enhanced suppressive activity. Ectopic expression of miR-17 imparted effector-T-cell-like characteristics to Treg cells via the de-repression of genes encoding effector cytokines. Thus, miR-17 provides a potent layer of Treg cell control through targeting Eos and additional Foxp3 co-regulators.

Amyloid-like amelogenin nanoribbons template mineralization via a low-energy interface of ion binding sites.

Protein scaffolds direct the organization of amorphous precursors that transform into mineralized tissues, but the templating mechanism remains elusive. Motivated by models for the biomineralization of tooth enamel, wherein amyloid-like amelogenin nanoribbons guide the mineralization of apatite filaments, we investigated the impact of nanoribbon structure, sequence, and chemistry on amorphous calcium phosphate (ACP) nucleation. Using full-length human amelogenin and peptide analogs with an amyloid-like domain, films of ß-sheet nanoribbons were self-assembled on graphite and characterized by in situ atomic force microscopy and molecular dynamics simulations. All sequences substantially reduce nucleation barriers for ACP by creating low-energy interfaces, while phosphoserines along the length of the nanoribbons dramatically enhance kinetic factors associated with ion binding. Furthermore, the distribution of negatively charged residues along the nanoribbons presents a potential match to the Ca­Ca distances of the multi-ion complexes that constitute ACP. These findings show that amyloid-like amelogenin nanoribbons provide potent scaffolds for ACP mineralization by presenting energetically and stereochemically favorable templates of calcium phosphate ion binding and suggest enhanced surface wetting toward calcium phosphates in general.

TRAF6 directs FOXP3 localization and facilitates regulatory T-cell function through K63-linked ubiquitination.

Regulatory T cells (Tregs) are crucial mediators of immune control. The characteristic gene expression and suppressive functions of Tregs depend considerably on the stable expression and activity of the transcription factor FOXP3. Transcriptional regulation of the Foxp3 gene has been studied in depth, but both the expression and function of this factor are also modulated at the protein level. However, the molecular players involved in posttranslational FOXP3 regulation are just beginning to be elucidated. Here, we found that TRAF6-deficient Tregs were dysfunctional in vivo; mice with Treg-restricted deletion of TRAF6 were resistant to implanted tumors and displayed enhanced anti-tumor immunity. We further determined that FOXP3 undergoes K63-linked ubiquitination at lysine 262 mediated by the E3 ligase TRAF6. In the absence of TRAF6 activity or upon mutation of the ubiquitination site, FOXP3 displayed aberrant, perinuclear accumulation and disrupted regulatory function. Thus, K63-linked ubiquitination by TRAF6 ensures proper localization of FOXP3 and facilitates the transcription factor's gene-regulating activity in Tregs. These results implicate TRAF6 as a key posttranslational, Treg-stabilizing regulator that may be targeted in novel tolerance-breaking therapies.

Co-Assembly of Carbon Nanotube Porins into Biomimetic Peptoid Membranes.

Robust and cost-effective membrane-based separations are essential to solving many global crises, such as the lack of clean water. Even though the current polymer-based membranes are widely used for separations, their performance and precision can be enhanced by using a biomimetic membrane architecture that consists of highly permeable and selective channels embedded in a universal membrane matrix. Researchers have shown that artificial water and ion channels, such as carbon nanotube porins (CNTPs), embedded in lipid membranes can deliver strong separation performance. However, their applications are limited by the relative fragility and low stability of the lipid matrix. In this work, we demonstrate that CNTPs can co-assemble into two dimension (2D) peptoid membrane nanosheets, opening up a way to produce highly programmable synthetic membranes with superior crystallinity and robustness. A combination of molecular dynamics (MD) simulations, Raman spectroscopy, X-ray diffraction (XRD), and atomic force microscopy (AFM) measurements to verify the co-assembly of CNTP and peptoids are used and show that it does not disrupt peptoid monomer packing within the membrane. These results provide a new option for designing affordable artificial membranes and highly robust nanoporous solids.

IFN-beta and EIF2AK2 are potential biomarkers for interstitial lung disease in anti-MDA5 positive dermatomyositis.

OBJECTIVE: DM with positive anti-melanoma differentiation-related gene 5 (MDA5) antibody is an autoimmune disease with multiple complications. Interstitial lung diseases (ILDs) are significantly associated with DM and are particularly related to MDA5+ DM. This article aims to explore potential molecular mechanisms and develop new diagnostic biomarkers for MDA5+ DM-ILD. METHODS: The series matrix files of DM and non-specific interstitial pneumonia (NSIP) were downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) was used to screen the common enriched pathways related to DM and NSIP. Next, the co-expressed differential expressed genes (co-DEGs) between MDA5+, MDA5- and NSIP groups were identified by Venn plots, and then selected for different enrichment analyses and protein-protein interaction (PPI) network construction. The mRNA expression levels of IFN-beta and EIF2AK2 were measured by RT-qPCR. The protein expression levels of IFN-beta were measured by ELISA. RESULTS: Using GSEA, the enriched pathway 'herpes simplex virus 1 infection' was both up-regulated in DM and NSIP. Enrichment analysis in MDA5+ DM, MDA5- DM and NSIP reported that the IFN-beta signalling pathway was an important influencing factor in the MDA5+ DM-ILD. We also identified that eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) was an important gene signature in the MDA5+ DM-ILD by PPI analysis. The expression levels of IFN-beta and EIF2AK2 were significantly increased in MDA5+ DM-ILD patients. CONCLUSIONS: IFN-beta and EIF2AK2 contributed to the pathogenesis of MDA5+ DM-ILD, which could be used as potential therapeutic targets.

Impact of climate factors and climate-gene interaction on systemic lupus erythematosus patients' response to glucocorticoids therapy.

BACKGROUND: Glucocorticoids (GCs) were the essential drugs for systemic lupus erythematosus (SLE). However, different patients differ substantially in their response to GCs treatment. Our current study aims at investigating whether climate variability and climate-gene interaction influence SLE patients' response to the therapy of GCs. METHODS: In total, 778 SLE patients received therapy of GCs for a study of 12-week follow-up. The efficacy of GCs treatment was evaluated using the Systemic Lupus Erythematosus Disease Activity Index. The climatic data were provided by China Meteorological Data Service Center. Additive and multiplicative interactions were examined. RESULTS: Compared with patients with autumn onset, the efficacy of GCs in patients with winter onset is relatively poor (ORadj = 1.805, 95%CIadj : 1.181-3.014, padj = 0.020). High mean relative humidity during treatment decreased the efficacy of GCs (ORadj = 1.033, 95%CIadj : 1.008-1.058, padj = 0.011), especially in female (ORadj = 1.039, 95%CIadj : 1.012-1.067, padj = 0.004). There was a significant interaction between sunshine during treatment and TRAP1 gene rs12597773 on GCs efficacy (Recessive model: AP = 0.770). No evidence of significant interaction was found between climate factors and the GR gene polymorphism on the improved GCs efficacy in the additive model. Multiplicative interaction was found between humidity in the month prior to treatment and GR gene rs4912905 on GCs efficacy (Dominant model: OR = 0.470, 95%CI: 0.244-0.905, p = 0.024). CONCLUSIONS: Our findings suggest that climate variability influences SLE patients' response to the therapy of GCs. Interactions between climate and TRAP1/GR gene polymorphisms were related to GCs efficacy. The results guide the individualized treatment of SLE patients.

Shape-preserving amorphous-to-crystalline transformation of CaCO3 revealed by in situ TEM.

Organisms use inorganic ions and macromolecules to regulate crystallization from amorphous precursors, endowing natural biominerals with complex morphologies and enhanced properties. The mechanisms by which modifiers enable these shape-preserving transformations are poorly understood. We used in situ liquid-phase transmission electron microscopy to follow the evolution from amorphous calcium carbonate to calcite in the presence of additives. A combination of contrast analysis and infrared spectroscopy shows that Mg ions, which are widely present in seawater and biological fluids, alter the transformation pathway in a concentration-dependent manner. The ions bring excess (structural) water into the amorphous bulk so that a direct transformation is triggered by dehydration in the absence of morphological changes. Molecular dynamics simulations suggest Mg-incorporated water induces structural fluctuations, allowing transformation without the need to nucleate a separate crystal. Thus, the obtained calcite retains the original morphology of the amorphous state, biomimetically achieving the morphological control of crystals seen in biominerals.

Spontaneous Lithiation of Binary Oxides during Epitaxial Growth on LiCoO2.

Epitaxial growth is a powerful tool for synthesizing heterostructures and integrating multiple functionalities. However, interfacial mixing can readily occur and significantly modify the properties of layered structures, particularly for those containing energy storage materials with smaller cations. Here, we show a two-step sequence involving the growth of an epitaxial LiCoO2 cathode layer followed by the deposition of a binary transition metal oxide. Orientation-controlled epitaxial synthesis of the model solid-state-electrolyte Li2WO4 and anode material Li4Ti5O12 occurs as WO3 and TiO2 nucleate and react with Li ions from the underlying cathode. We demonstrate that this lithiation-assisted epitaxy approach can be used for energy materials discovery and exploring different combinations of epitaxial interfaces that can serve as well-defined model systems for mechanistic studies of energy storage and conversion processes.

Association between air pollution exposure and outpatient visits for dermatomyositis in a humid subtropical region of China: a time-series study.

In recent years, a growing number of studies have found that air pollution plays critical roles in the onset and development of autoimmune diseases, but few studies have shown an association between air pollutants and dermatomyositis (DM). We sought to investigate the relationship between short-term exposure to air pollution and outpatient visits for DM and to quantify the burden of DM due to exposure to air pollutants in Hefei, China. Daily records of hospital outpatient visits for DM, air pollutants and meteorological factors data in Hefei from January 1, 2018 to December 31, 2021 were obtained. We used a distributed lag non-linear model (DLNM) in conjunction with a generalized linear model (GLM) to explore the association between air pollution and outpatient visits for DM, and conducted stratified analyses by gender, age and season. Moreover, we used attributable fraction (AF) and attributable number (AN) to reflect the burden of disease. A total of 4028 DM clinic visits were recorded during this period. High concentration nitrogen dioxide (NO2) exposure was associated with increased risk of DM outpatient visits (relative risk (RR) 1.063, 95% confidence interval (CI) 1.015-1.114, lag 0-5). Intriguingly, exposure to high concentration ozone (O3) was associated with reduced risk of outpatient visits for DM (RR 0.974, 95% CI 0. 0.954-0.993, lag 0-6). The results of stratified analyses showed that the cold season (vs. warm season) were more susceptible to outpatient visits for DM associated with NO2 and O3 exposure. In addition, we observed that an increased risk of DM outpatient visits was attributable to high concentration NO2 exposure, while high concentration O3 exposure was associated with a decreased risk of DM outpatient visits. This study provided a scientific basis for the etiology research and health protection of DM.

Multi-Step Nucleation of a Crystalline Silicate Framework via a Structurally Precise Prenucleation Cluster.

Hierarchical nucleation pathways are ubiquitous in the synthesis of minerals and materials. In the case of zeolites and metal-organic frameworks, pre-organized multi-ion "secondary building units" (SBUs) have been proposed as fundamental building blocks. However, detailing the progress of multi-step reaction mechanisms from monomeric species to stable crystals and defining the structures of the SBUs remains an unmet challenge. Combining in situ nuclear magnetic resonance, small-angle X-ray scattering, and atomic force microscopy, we show that crystallization of the framework silicate, cyclosilicate hydrate, occurs through an assembly of cubic octameric Q3 8 polyanions formed through cross-linking and polymerization of smaller silicate monomers and other oligomers. These Q3 8 are stabilized by hydrogen bonds with surrounding H2 O and tetramethylammonium ions (TMA+ ). When Q3 8 levels reach a threshold of ≈32 % of the total silicate species, nucleation occurs. Further growth proceeds through the incorporation of [(TMA)x (Q3 8 )⋅n H2 O](x-8) clathrate complexes into step edges on the crystals.

The deubiquitinase USP44 promotes Treg function during inflammation by preventing FOXP3 degradation.

The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis. Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination. However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct induced Treg (iTreg) lineage, remain unclear. Here, we identify the ubiquitin-specific peptidase 44 (USP44) as a novel deubiquitinase for FOXP3. USP44 interacts with and stabilizes FOXP3 by removing K48-linked ubiquitin modifications. Notably, TGF-ß induces USP44 expression during iTreg differentiation. USP44 co-operates with USP7 to stabilize and deubiquitinate FOXP3. Tregs genetically lacking USP44 are less effective than their wild-type counterparts, both in vitro and in multiple in vivo models of inflammatory disease and cancer. These findings suggest that USP44 plays an important role in the post-translational regulation of Treg function and is thus a potential therapeutic target for tolerance-breaking anti-cancer immunotherapy.

The energetic basis for hydroxyapatite mineralization by amelogenin variants provides insights into the origin of amelogenesis imperfecta.

Small variations in the primary amino acid sequence of extracellular matrix proteins can have profound effects on the biomineralization of hard tissues. For example, a change in one amino acid within the amelogenin protein can lead to drastic changes in enamel phenotype, resulting in amelogenesis imperfecta, enamel that is defective and easily damaged. Despite the importance of these undesirable phenotypes, there is very little understanding of how single amino acid variation in amelogenins can lead to malformed enamel. Here, we aim to develop a thermodynamic understanding of how protein variants can affect steps of the biomineralization process. High-resolution, in situ atomic force microscopy (AFM) showed that altering one amino acid within the murine amelogenin sequence (natural variants T21 and P41T, and experimental variant P71T) resulted in an increase in the quantity of protein adsorbed onto hydroxyapatite (HAP) and the formation of multiple protein layers. Quantitative analysis of the equilibrium adsorbate amounts revealed that the protein variants had higher oligomer-oligomer binding energies. MMP20 enzyme degradation and HAP mineralization studies showed that the amino acid variants slowed the degradation of amelogenin by MMP20 and inhibited the growth and phase transformation of HAP. We propose that the protein variants cause malformed enamel because they bind excessively to HAP and disrupt the normal HAP growth and enzymatic degradation processes. The in situ methods applied to determine the energetics of molecular level processes are powerful tools toward understanding the mechanisms of biomineralization.

Short-term association of NO2 with hospital visits for chronic kidney disease and effect modification by temperature in Hefei, China: A time series study.

BACKGROUND: A large body of evidence has linked air pollution and temperature with chronic kidney disease (CKD) prevalence and hospitalizations. However, most studies have focused on the influence of heat stress on CKD prevalence, and the potential effect modification of temperature on the association between air pollution and CKD has not been well-investigated. In this study, we examined the associations of the whole temperature spectrum and air pollution with CKD-related hospital visits and explored whether temperature modifies the short-term association of air pollution with CKD-related hospital visits. METHODS AND FINDINGS: We collected 40 276 CKD-related hospital visits from the first Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital in Hefei, China, during 2015-2019. A two-stage time-series design was conducted to investigate the associations of air pollution and daily mean temperature with CKD-related hospital visits. First, we estimated the associations between air pollution and CKD-related hospital visits as well as temperature and CKD-related hospital visits. Second, we analyzed the associations of air pollution with CKD hospital visits at different temperatures. We found that NO2 exposure and low temperature were associated with an increased risk of CKD-related hospital visits. Low temperature enhanced the association between NO2 exposure and CKD-related hospital visits, with an increase of 4.30% (95% CI: 2.47-5.92%) per 10 µg/m3 increment in NO2 at low temperature. Effect modification of the association between NO2 and the risk of CKD-related hospital visits was stronger at low temperature across the whole population. CONCLUSIONS: Our findings indicate that low temperature-related chronic kidney damage should be of immediate public health concern. Impact of NO2 exposure on the risk of CKD-related hospital visits may increase under the low temperature, which suggests the need for NO2 exposure mitigation strategies in the context of climate change and an enhanced understanding of the mechanisms underlying the temperature variance of air pollution effect to help reduce the magnitude of the CKD burden on the healthcare systems.

Chromatin accessibility landscapes of immune cells in rheumatoid arthritis nominate monocytes in disease pathogenesis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that involves a variety of cell types. However, how the epigenetic dysregulations of peripheral immune cells contribute to the pathogenesis of RA still remains largely unclear. RESULTS: Here, we analysed the genome-wide active DNA regulatory elements of four major immune cells, namely monocytes, B cells, CD4+ T cells and CD8+ T cells, in peripheral blood of RA patients, osteoarthritis (OA) patients and healthy donors using Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq). We found a strong RA-associated chromatin dysregulation signature in monocytes, but no other examined cell types. Moreover, we found that serum C-reactive protein (CRP) can induce the RA-associated chromatin dysregulation in monocytes via in vitro experiments. And the extent of this dysregulation was regulated through the transcription factor FRA2. CONCLUSIONS: Together, our study revealed a CRP-induced pathogenic chromatin dysregulation signature in monocytes from RA patients and predicted the responsible signalling pathway as potential therapeutic targets for the disease.

Peptoid-Directed Formation of Five-Fold Twinned Au Nanostars through Particle Attachment and Facet Stabilization.

While bio-inspired synthesis offers great potential for controlling nucleation and growth of inorganic particles, precisely tuning biomolecule-particle interactions is a long-standing challenge. Herein, we used variations in peptoid sequence to manipulate peptoid-Au interactions, leading to the synthesis of concave five-fold twinned, five-pointed Au nanostars via a process of repeated particle attachment and facet stabilization. Ex situ and liquid-phase TEM observations show that a balance between particle attachment biased to occur near the star points, preferential growth along the [100] direction, and stabilization of (111) facets is critical to forming star-shaped particles. Molecular simulations predict that interaction strengths between peptoids and distinct Au facets differ significantly and thus can alter attachment kinetics and surface energies to form the stars. This work provides new insights into how sequence-defined ligands affect particle growth to regulate crystal morphology.

Systemic lupus erythematosus patients have a distinct structural and functional skin microbiota compared with controls.

OBJECTIVE: The skin is the second most affected organ after articular involvement in systemic lupus erythematosus (SLE) patients. Cutaneous involvement occurs in approximately 80% of patients during the course of SLE. Interaction between the host and skin microorganism is a complex process. There are few studies on the diversity of skin microbes in SLE patients. Therefore, this study aims to explore the relationship between skin microorganisms and SLE. METHODS: A total of 20 SLE patients, 20 controls with rosacea and 20 healthy controls were selected as study subjects. Both the skin microbiota of rash region and non-rash region for each SLE patient were collected.16S rRNA gene sequencing was used to detected skin microbiota from 80 specimens. α-Diversity and ß-diversity of skin microbiota were analyzed based on operational taxonomic units (OTUs) and minimal entropy decomposition (MED). Using Wilcoxon test and Linear Discriminate Analysis Effect Size (LEfSe), skin microbial diversity and composition were analyzed. Functional capabilities of microbiota were estimated through Kyoto Encyclopedia of Genes and Genomes database. RESULTS: Compared to rash region of SLE, diversity and richness were increased in healthy controls, and decreased in non-rash region of SLE and rash region of controls with rosacea. Additionally, changes of skin microbial composition were found at different taxonomic levels between four groups. For example, genus Halomonas was increased and genera Pelagibacterium, Novosphingobium, and Curvibacter were decreased in rash region compared to non-rash region of SLE based on OTUs and MED. Based on OTUs, metabolic pathways were also found differences in SLE patients, such as Xenobiotics Biodegradation and Metabolism. CONCLUSION: Compositions and diversity of skin microbiota in SLE patients are changed. This pilot study provides some suggestive evidence for further exploration of skin microbiota in SLE patients with cutaneous involvement.

Prevalence and influential factors of thrombocytopaenia in systemic lupus erythematosus patients: a retrospective analysis of 3140 cases in a Chinese population.

INTRODUCTION: The present study aimed to investigate the prevalence and influential factors of thrombocytopaenia in systemic lupus erythematosus (SLE) patients among the Chinese population in order to provide evidence for improving the treatment and nursing of SLE patients. METHODS: A retrospective analysis of 3140 SLE patients admitted to two large tertiary hospitals was conducted in Anhui, China, from 2011 to 2018. In addition, the influential factors related to SLE with thrombocytopaenia were analysed through univariate and multivariate analysis. RESULTS: A total of 804 SLE patients had thrombocytopaenia (25.6%). The top 5 clinical manifestations of SLE inpatients were proteinuria (51.0%), lupus nephritis (45.9%), new rash (38.4%), haematuria (36.7%) and pyuria (32.2%). The incidence of neurological manifestations, oral mucosal ulceration, pleurisy, pericarditis, hyperglycaemia, leucocytopaenia, urinary casts, haematuria, pyuria and high disease activity in the thrombocytopaenia group were higher than those in the non-thrombocytopaenia group (p < 0.05). Multivariate analysis showed age (odds ratio (OR) = 1.009, p = 0.005), neurological manifestations (OR = 1.373, p = 0.048), pericarditis (OR = 1.394, p = 0.048), hyperglycaemia (OR = 1.717, p < 0.001), leucocytopaenia (OR = 2.551, p < 0.001), haematuria (OR = 1.582, p < 0.001), serum C3 level <0.85 g/L (OR = 1.525, p = 0.001), serum C4 concentration <0.10 g/L (OR = 1.287, p = 0.020), serum CRP concentration <8 ng/L (OR = 1.314, p = 0.005), prothrombin time >15.30 seconds (OR = 1.479, p = 0.032), activated partial thromboplatin time >45 seconds (OR = 1.924, p < 0.001) and thrombin time >21 seconds (OR = 1.629, p = 0.015) were associated with thrombocytopaenia. CONCLUSION: Thrombocytopaenia has a high prevalence in SLE patients and is related to some baseline, clinical and laboratory characteristics, affecting multiple organs and systems.

Natural products action on pathogenic cues in autoimmunity: Efficacy in systemic lupus erythematosus and rheumatoid arthritis as compared to classical treatments.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by self-perpetuating inflammation and tissue/organ damage, resulting from the failure of lymphocyte auto-tolerance, cause morbidity and mortality worldwide. The current drugs or therapies including conventional non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), as well as several biologic therapies such as B cell-targeted, T cell-targeted, cytokines-targeted and cytokines receptors-targeted therapy, cannot completely cure SLE and RA, and are always accompanied by unexpected side effects. Therefore, more studies have explored new methods for therapy and found that the herbal medicine as well as its natural products (NPs) exhibited promising therapeutic value through exerting effects of immunomodulation, anti-inflammation, anti-oxidation, and anti-apoptosis, etc. via regulating abnormal responses in kidney, innate and adaptive immune systems, intestine, synoviocytes, as well as bone system including chondrocytes, osteoclasts, joints and paw tissues. In the present review, we will elucidate the current mainstream drugs and therapies for SLE and RA, and summarize the efficacy and mechanisms of NPs in the treatment of SLE and RA based on available findings including in vitro and in vivo animal models, as well as clinical studies, and further analyze the existing challenges, in order to provide comprehensive evidence for improvement of SLE and RA therapy by NPs and to promote management of these two autoimmune diseases.

Hsp70 Gene Polymorphisms Are Associated With Disease Susceptibility and HRQOL Improvement in Chinese Han Population With Systemic Lupus Erythematosus.

OBJECTIVES: The aim of this study is to investigate whether heat shock protein 70 (Hsp70) gene polymorphisms are implicated in systemic lupus erythematous (SLE) susceptibility, the efficacy of glucocorticoids (GCs) treatment, and improvement of health-related quality of life. METHODS: A total of 499 SLE patients and 499 controls were included in a case-control study, and 468 SLE patients treated with GCs for 12 weeks were involved in a follow-up study. Patients who completed the 12-week follow-up were divided into GCs-sensitive and GCs-insensitive group by using the SLE disease activity index. The SF-36 was used to evaluate the health-related quality of life of SLE patients, and genotyping was performed by improved multiplex ligation detection reaction. RESULTS: rs2075800 was associated with SLE susceptibility (adjusted odds ratio [ORadj], 1.437; 95% confidence interval [CI], 1.113-1.855; Padj = 0.005; PBH = 0.020 by dominant model; ORadj, 1.602; 95% CI, 1.072-2.395; Padj = 0.022; PBH = 0.029 by TT vs CC model; ORadj = 1.396; 95% CI = 1.067-1.826; Padj = 0.015; PBH = 0.029 by TC vs CC model). In the follow-up study, rs2075799 was associated with the improvement in mental health (p = 0.004, PBH = 0.044), but we failed to find any association between the efficacy of GCs and Hsp70 gene polymorphisms. CONCLUSIONS: Hsp70 gene polymorphisms may be associated with susceptibility to SLE and improvement of mental health in Chinese Han population.

Copy number variations and polymorphisms in HSP90AB1 and risk of systemic lupus erythematosus and efficacy of glucocorticoids.

The aim of our study was to assess the associations of HSP90AB1 copy number variations (CNVs) with systemic lupus erythematosus (SLE) risk and glucocorticoids (GCs) efficacy, as well as the relationship between HSP90AB1 single-nucleotide polymorphisms (SNPs) and GCs efficacy. HSP90AB1 CNVs and SLE risk were analysed in 519 patients and 538 controls. Patients treated with GCs were followed up for 12 weeks and were divided into sensitive and insensitive groups to investigate the effects of CNVs (419 patients) and SNPs (457 patients) on the efficacy of GCs. Health-related quality of life (HRQoL) was also measured by SF-36 at baseline and week 12 to explore the relationship between CNVs/SNPs and HRQoL improvements in Chinese SLE patients. Our results indicated a statistically significant association between HSP90AB1 CNVs and SLE (PBH  = 0.039), and this association was more pronounced in the female subgroup (PBH  = 0.039). However, we did not detect association of HSP90AB1 CNVs/SNPs with efficacy of GCs. But we found a marginal association between SNP rs13296 and improvement in Role-emotional, while this association was not strong enough to survive in the multiple testing corrections. Collectively, our findings suggest that the copy number of HSP90AB1 is associated with SLE susceptibility. But copy number and polymorphisms of HSP90AB1 may not be associated with efficacy of GCs.