Expression of Toll-like receptors 2 and 4 in the saliva of patients with systemic lupus erythematosus and chronic periodontitis

Objective

The aim of this study was to investigate the expression of salivary Toll-like receptors (TRL) 2 and 4 in patients with systemic lupus erythematosus (SLE) and chronic periodontitis (CP).

Methods

A case-control study was conducted with 77 participants (42 SLE and 35 non-SLE) stratified according to CP diagnosis criteria. Periodontal parameters consisted of clinical attachment level (CAL), probing depth (PD), the visible plaque index (VPI), and the gingival bleeding index (GBI). Salivary TRL 2 and 4 expressions were determined by quantitative real-time polymerase chain reaction (RT-PCR). Statistical analysis included Mann-Whitney U test, Kruskal-Wallis test, Spearman’s correlation rank, and multiple linear regression.

Results

Patients with isolated SLE or CP had higher TLR 2 and TLR 4 expression in their saliva samples (P?<?0.05). The group with both SLE and CP had lower TLR 2 and 4 expressions (P?<?0.05). TLR 2 and TLR 4 showed significant negative correlations with PD, CAL, and GBI in SLE patients, and a significant positive correlation with periodontal parameters in non-SLE patients. CP was independently associated with reduction of TLR2 and TLR4 expression, even after adjusting for clinical data and current drug use.

Conclusion

Reduced TRL 2 and 4 expression in saliva was associated with the presence of CP in SLE patients.

Pregnancy rates and perinatal outcomes in women with systemic lupus erythematosus: data from the Korean national health claims database

Introduction/Objectives

The pregnancy rate in systemic lupus erythematosus (SLE) is not fully understood and comparisons of adverse pregnancy outcomes (APOs) with SLE versus the general population are limited. This study aimed to estimate the pregnancy rate and APOs in Korean SLE compared to those without SLE.

Method

Pregnant women were identified using the ICD-10 codes for delivery and abortion in the Korean national health claims database (2013–2015). APOs were classified as fetal loss, intrauterine growth retardation (IUGR), pre-eclampsia/eclampsia, and gestational diabetes. Annual incidence rates (IRs) of pregnancy and APOs were calculated in women with SLE and the general population without SLE and the two groups were compared using age-adjusted incidence rate ratios (IRRs). Age-stratified IRRs were further analyzed.

Results

The annual IRs of pregnancy in SLE were 29.54–30.70 per 1000 persons. The IRRs were lower in women with SLE than in the general population: 0.68 (0.61–0.76), 0.66 (0.60–0.74), and 0.74 (0.66–0.82) in each respective year. The IRRs of fetal loss, IUGR, and pre-eclampsia/eclampsia were 1.30 (1.14–1.49), 4.65 (3.55–6.09), and 3.43 (2.70–4.36), respectively. However, the IRR of gestational diabetes in SLE did not significantly differ from that of women without SLE. Among the APOs, fetal loss, IUGR, and pre-eclampsia/eclampsia showed decreasing tendencies as age increased.

Conclusions

Pregnancy rates in SLE were approximately 30% lower than those in the general population. Except for gestational diabetes, fetal loss, IUGR, and pre-eclampsia/eclampsia were higher in SLE and showed a decreasing tendency with age.

MiR-325 Promotes Oxaliplatin-Induced Cytotoxicity Against Colorectal Cancer Through the HSPA12B/PI3K/AKT/Bcl-2 Pathway

Background

Oxaliplatin is one of the most effective chemotherapeutic drugs used for the treatment of colorectal cancer (CRC). However, intervention that attenuates the resistance of oxaliplatin is still required in the treatment of CRC.

Aims

To investigate the role of miR-325 in changing the oxaliplatin sensitivity to CRC cells.

Methods

Expression of miR-325 in colorectal cancer tissues and cell lines was measured by using qRT-PCR analysis. Cytotoxicity of oxaliplatin to control or miR-325-overexpressed HT29 and SW480 cells was evaluated by CCK-8 assays. Luciferase reporter assay was used to confirm the regulation of miR-325 on HSPA12B. Flow cytometry was performed to detect the mitochondrial membrane potential and cell apoptosis.

Results

Expression of miR-325 was decreased in colorectal cancer tissues and cell lines. However, overexpression of miR-325 can decrease the 50% inhibiting concentration of oxaliplatin to colorectal cancer cell lines HT29 and SW480. Mechanically, we confirmed that miR-325 targeted HSPA12B in colorectal cancer. Therefore, overexpression of miR-325 inhibited the phosphorylation of PI3K and AKT and decreased the expression of Bcl-2 to promote the oxaliplatin-induced mitochondrial apoptosis in colorectal cancer.

Conclusions

MiR-325 sensitizes the colorectal cancer cells to oxaliplatin-induced cytotoxicity through the HSPA12B/PI3K/AKT/Bcl-2 pathway.

     

Several critical genes and microRNAs associated with the development of polycystic ovary syndrome

BackgroundWe aimed to identify key genes and microRNAs (miRNAs) associated with the development of polycystic ovary syndrome (PCOS).MethodsGSE84376 mRNA microarray data (15 PCOS granulosa cells and 13 control granulosa cells) and GSE34526 mRNA microarray data (7 PCOS granulosa cells and 3 control granulosa cells) were downloaded from the Gene Expression Omnibus (GEO) database. First, differentially expressed gene (DEG) analysis, gene set enrichment analysis (GSEA) for differentially expressed mRNAs, and protein–protein interaction (PPI) network analysis were conducted. Next, miRNA-target genes were analyzed and functions predicted, and a competing endogenous RNA (ceRNA) network was constructed. Finally, the relationship between miR-486-5p and PRELID2 was experimentally validated.ResultsSpleen tyrosine kinase (SYK), major histocompatibility complex, class II, DR alpha (HLA-DRA), and interleukin 10 (IL-10) were important nodes in the PPI network. Interestingly, HLA-DRA was significantly enriched in phagosomes mediated by Staphylococcus aureus infection, and in IL-10 enriched during S. aureus infection. One miRNA (miR-486-5p) and a single target gene (PRELID2) were obtained from the ceRNA network. Further experiments showed that miR-486-5p is upregulated and PRELID2 is downregulated in PCOS patient granulosa cells, and that miR-486-5p targets the PRELID2 3′UTR. Topological property analysis showed that hsa-miR-4687-5p downregulation and hsa-miR-4651 upregulation determined the levels of most mRNAs. Levels of the hsa-miR-4651 target gene were significantly enriched in the leukocyte transendothelial migration pathway.ConclusionsOur results suggest that HLA-DRA and IL-10 may contribute to PCOS progression via phagosome enriched by S. aureus infection, while miR-486-5p may be implicated in follicular development in PCOS by targeting PRELID2. Besides, miR-4651 may be involved in inflammation via leukocyte transendothelial migration, by regulating its target gene. These findings may indicate new directions and constitute a breakthrough in studying the pathophysiology of PCOS.     

T-cell proliferation by surface molecules expression on polymorphonuclear neutrophils stimulated with IL-4 in superantigen presence

BackgroundPolymorphonuclear neutrophils (PMNs) were originally described as short lived and terminally differentiated phagocytes that contribute only to the innate immune response. Some studies of PMNs cytokine production and expression of numerous cell surface proteins has suggested that PMNs are likely to influence adaptive responses and may satisfy the criteria of antigen presenting cells.Aim of the studyThis work aimed to study the effect of IL-4 in the function of PMNs as antigen presenting cells.MethodsFlow cytometry was used in the present study for the detection of cell surface human leukocyte antigen (HLA) class II, CD80 and CD86 required for antigen presentation and subsequent T-cell activation in the presence of Staphylococcus aureus enterotoxin (A). Human peripheral blood neutrophils were used for this purpose.ResultsThis study has shown that IL-4 stimulated PMNs for 24 h expressed HLA class II, CD80 and CD86 that involved in antigen presentation. It also indicated that co-cultivation of IL-4 stimulated PMNs with autologous T-cells and in the presence of S. aureus enterotoxin (A) induced T-cell proliferation.ConclusionsIn vitro stimulation of PMNs with IL-4 showed expression of surface molecules involved in antigen presentation. In addition, the co-culture of T-Cells and stimulated PMNs showed high T-Cells proliferation in the presence of superantigens.     

Clinicopathological features and outcomes of SLE patients with renal injury characterised by thrombotic microangiopathy

Objectives

Non-immune complex (IC)-mediated renal thrombotic microangiopathy (TMA) has been reported in patients with systemic lupus erythematosus (SLE), but most studies included patients with both renal TMA and IC-mediated lupus nephritis (LN). In this study, the clinicopathological features and outcomes of renal injury characterised by only renal TMA were retrospectively analyzed.

Methods

Patients with glomerular and/or vascular TMA in the absence of subendothelial or epithelial immune deposits were screened from 2,332 biopsied of SLE patients. The TMA lesions were divided into glomerular, vascular or both. Acute tubular-interstitial injury was semi-quantitatively analyzed. The podocyte foot process effacement (FPE) was measured by electronic microscopy.

Results

Two hundred fifty-seven (11.0%) renal biopsies revealed TMA, among which 237 biopsies showed TMA coexisting with LN, and 20 (0.9%) biopsies had only renal TMA without or with only mesangial immune deposits. All patients manifested with acute kidney injury and haematological disorders. Among them, 11 (55%) required renal replacement therapy, 12 (60%) had nephrotic syndrome and 13 (65.0%) showed microvascular haemolytic anaemia with thrombocytopenia. Seventeen (85%) biopsies revealed both glomerular TMA and vascular TMA, two had only glomerular TMA and one had vascular TMA. Eight (40%) had no glomerular immune deposits and 12 (60%) showed only mesangial immune deposits. The acute tubulointerstitial injury in patients requiring dialysis was more severe than those not needing dialysis ((43.6 ± 24.9) % vs. (21.7 ± 20.1) %, p = 0.047). FPE of podocytes was positively correlated with proteinuria (r² = 0.347, p = 0.006). All patients received high-dose methylprednisolone pulse therapy. Four patients received plasma exchange. The renal function of 11 patients requiring dialysis initially recovered after 16.0 (interquartile range [IQR] 9.0, 30.0) days of treatment. During the follow-up of 58.0 (IQR 36.0, 92.3) months, remission was achieved in 19 (95%) patients; only one patient had no response. No patient died or progressed to end-stage renal disease; six patients (30%) relapsed.

Conclusion

Renal TMA, usually accompanying severe renal injury, was not uncommon in SLE patients with renal disease and should be distinguished from immune complex–mediated severe classes of LN. Early intensive immunosuppressive treatment may be associated with a good long-term renal outcome.

Low estimated glomerular filtration rate is an independent risk factor for higher hydroxychloroquine concentration

Background

The aim of this study was to analyze the relationship of the estimated glomerular filtration rate (eGFR) to hydroxychloroquine (HCQ) blood concentrations in systemic lupus erythematosus (SLE) patients.

Method

Patients with SLE who had been taking HCQ for more than 12 months were recruited. All subjects gave written informed consent. Various clinical characteristics and laboratory values were examined. The blood concentration of HCQ was measured by high-performance liquid chromatography, and the relationship of eGFR to HCQ blood concentration was mainly investigated.

Result

In total, 115 patients with SLE receiving long-term HCQ therapy were included in the study. The median concentration of HCQ was 1096 ng/ml (range 116–8240 ng/ml). The eGFR was strongly associated with blood concentration of HCQ (P = 0.011, P < 0.05), when adjusted for age, sex, body mass index (BMI), weight-adjusted dose, prednisone use and immunosuppressive drug use. No statistically significant association were found between age, duration, BMI, weight-adjusted HCQ dose, corticosteroid use, immunosuppressant use and blood concentrations of HCQ.

Conclusion

We provided novel evidence that impaired renal function influenced the blood concentration of HCQ. Patients with low eGFR need to adjust the HCQ dosage according to the monitoring results of HCQ blood concentrations.

Infección del sistema nervioso central por Listeria monocytogenes en pacientes con lupus eritematoso sistémico: análisis de 26 casos,incluyendo el reporte de un caso nuevo

IntroductionInfections in patients with systemic lupus erythematosus cause significant morbidity. Infection due to Listeria monocytogenes (LM) is considered an opportunistic disease, and has been published on rare occasions in patients with SLE.ObjectiveTo review the presentation of listeria infections in the central nervous system (CNS) in SLE patients.MethodologyWe conducted a literature review, selecting cases with central nervous system infection and confirmation of LM infection through culture.ResultsTwenty six cases are described. The most common presentation was meningitis, with meningoencephalitis and brain abscesses being less frequent. The predisposing factors are: use of glucocorticoids, immunosuppressants, renal replacement therapy and the activity flares.ConclusionCNS infection by listeria is rare and sometimes fatal. The atypical presentation may lead to a delay in diagnosis and appropriate treatment. L. monocytogenes should be included in the differential diagnosis of patients with SLE with neurological manifestations.     

Regulation of leukocyte-endothelium interaction and leukocyte transendothelial migration by intercellular adhesion molecule 1-fibrinogen recognition.

Although primarily recognized for its role in hemostasis, fibrinogen is also required for competent inflammatory reactions in vivo. It is now shown that fibrinogen promotes adhesion to and migration across an endothelial monolayer of terminally differentiated myelomonocytic cells. This process does not require chemotactic/haptotactic gradients or cytokine stimulation of the endothelium and is specific for the association of fibrinogen with intercellular adhesion molecule 1 (ICAM-1) on endothelium. Among other adhesive plasma proteins, fibronectin fails to increase the binding of leukocytes to endothelium, or transendothelial migration, whereas vitronectin promotes the binding but not the migration. The fibrinogen-mediated leukocyte adhesion and transendothelial migration could be inhibited by a peptide from the fibrinogen gamma-chain sequence N117NQKIVNL-KEKVAQLEA133, which blocks the binding of fibrinogen to ICAM-1. This interaction could also be inhibited by new anti-ICAM-1 monoclonal antibodies that did not affect the ICAM-1-CD11a/CD18 recognition, thus suggesting that the fibrinogen binding site on ICAM-1 may be structurally distinct from regions previously implicated in leukocyte-endothelium interaction. Therefore, binding of fibrinogen to vascular cell receptors is sufficient to initiate (i) increased leukocyte adhesion to endothelium and (ii) leukocyte transendothelial migration. These two processes are the earliest events of immune inflammatory responses and may also contribute to atherosclerosis.     

Lupus erythematosus tumidus (LET) with autoimmune thyroid dysfunction (AITD) as the first presentation of systemic lupus erythematosus: A case report and review of the literature

IntroductionLupus erythematosus tumidus (LET) is a rare cutaneous manifestation especially as a first presentation of systemic lupus erythematosus (SLE). Autoimmune thyroid dysfunction (AITD) may be associated with SLE but rarely at initial presentation, and its diagnosis may be delayed.Case reportA 29 year old male presented to Tishreen Hospital in Damascus with a three-year history of recurrent cellulitis-like lesions on the face, and more recently, he developed similar lesions on the trunk and the chest, in addition to the development of peripheral and scrotal edema, constipation, xeroderma, hair loss, musculoskeletal pain and depression. Laboratory investigations revealed: leukopenia, anaemia, elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Immunological tests identified the positive anti-nuclear antibody (ANA), anti-double stranded DNA (anti-dsDNA), anti Ro/SSA, anti La/SSB antibodies. Additionally, there was consumed complement C3, elevated thyroid stimulating hormone (TSH), thyroid hormones decreased free T3 and T4 and anti-thyroid peroxidase (anti-TPO) antibody was positive. Skin biopsy from the cheek plaque suggested the presence of LET and revealed slight hyperkeratosis; actinic elastosis, telangiectasia and edema of the papillary dermis; deep dermis perivascular and periadnexal inflammatory infiltrates with karyorrhexis of the lymphocytes and dermis edema between strands of collagen. The patient fulfilled the SLE classification criteria and consequently, methylprednisolone, azathioprine, hydroxychloroquine, levothyroxine were introduced with dramatic improvement.ConclusionLET is a rare cutaneous lupus-specific lesion that may be associated with SLE. AITD, hypothyroidism in particular, could be an initial presentation of SLE. Increased awareness and early diagnosis of such clinical presentations may improve patient outcomes.     

Association between Duffy antigen receptor expression and disease severity in sickle cell disease patients

Objectives: Sickle cell disease (SCD) is associated with a pro-inflammatory state, characterized by an elevated baseline leukocyte count and inflammatory cytokines. Inflammation, white blood cell (WBC) adhesion to vascular endothelium with subsequent endothelial injury, and repeated ischemia–reperfusion injury contribute to disease pathogenesis. Identification of genetic polymorphisms that may modulate disease severity in SCD is becoming a field of interest. The Duffy blood group antigen has been identified as a receptor for various chemokines involved in neutrophil activation and trafficking. This study aimed at investigating the effect of RBCs’ Duffy antigen expression and its genetic polymorphisms on modulating disease severity and its complications among Egyptian sickle cell patients.

Methods

We analyzed the association of Duffy genotypes and phenotypes with clinical expression of SCD in 100 Egyptian patients. The Duffy phenotype expression was detected by indirect anti-globulin test while Duffy genotyping was conducted with polymerase chain reaction-restriction fragment length polymorphism-based assay.

Results

Total WBC count was strongly associated with Duffy genotype. WBCs were significantly higher in Duffy-positive patients (P?=?0.002). No statistical significance was evident between individual measures of disease severity (pulmonary dysfunction, avascular necrosis, central nervous system dysfunction, kidney dysfunction, and leg ulcers) and Duffy genotype.

Conclusion

Our study suggests that RBC Duffy expression increases levels of WBCs in SCD patients and that Duffy genotype may not be a potential biomarker for end-organ damage in SCD.     

Dysfunction of TRIM21 in interferon signature of systemic lupus erythematosus

Abstract

Objectives: TRIM21 is an E3 ubiquitin ligase for interferon regulatory factors (IRFs) that are involved in innate and acquired immunity. Here, we evaluated the role of TRIM21 in the interferon (IFN) signature of systemic lupus erythematosus (SLE).

Methods: Twenty SLE patients and 24 healthy controls were enrolled in this study. We analyzed mRNA expression of TRIM21, type I IFN, and IFN-inducible genes in peripheral blood mononuclear cell (PBMC). The protein levels of IRFs were assessed by Western blotting in PBMCs cultured with or without MG-132.

Results: The expression of TRIM21 mRNA and protein was significantly higher in SLE PBMCs as compared to healthy controls. There was a correlation between TRIM21 mRNA expression and SLE activities. In contrast to a negative correlation between mRNA expression level of TRIM21 and those of type I IFNs in healthy controls, we found a positive correlation between them in anti-TRIM21 antibody-positive SLE patients. Neither positive nor negative correlation was observed in the autoantibody-negative SLE patients. Western-blotting analysis revealed impaired ubiquitin-dependent proteasomal degradation of IRFs in SLE PBMCs.

Conclusion: Our study showed ubiquitin-dependent proteasomal degradation of IRFs was impaired in anti-TRIM21 antibody-dependent and -independent fashions, leading to amplification of IFN signature in SLE.     

ADAMTS7 Attenuates House Dust Mite-Induced Airway Inflammation and Th2 Immune Responses

Purpose

ADAMTS7 is a secreted metalloproteinase enzyme and proteoglycan associated with the early progression of coronary artery disease. However, there is limited information regarding the role of ADAMTS7 in lung adaptive immunity and inflammation. Thus, we sought to assess whether ADAMTS7 expression in the lung modulates house dust mite (HDM)-induced airway inflammation and Th2 immune response.

Methods

The role of ADAMTS7 in HDM-induced airway disease was assessed in ADAMTS7-deficient (ADAMTS7^?/?) mice and compared with the wild-type control mice by flow cytometry, ELISA, and histopathology. Furthermore, the antigen priming capability of dendritic cells (DC) was determined ex vivo by employing coculture with CD4⁺ OT-II cells.

Results

ADAMTS7^?/? mice develop an augmented eosinophilic airway inflammation, mucous cell metaplasia, and increased Th2 immune response to inhaled HDM. In addition, allergen uptake by lung DC and migration to draining mediastinal lymph node were significantly increased in ADAMTS7^?/? mice, which shows an enhanced capacity to mount allergen-specific T-cell proliferation and effector Th2 cytokine productions. We propose that the mechanism by which ADAMTS7 negatively regulates DC function involves attenuated antigen uptake and presentation capabilities, which reduces allergic sensitization and Th2 immune responses in the lung.

Conclusion

In aggregate, we provide compelling evidence that ADAMTS7 plays a pivotal role in allergic airway disease and Th2 immunity and would be an attractive target for asthma.

     

A systematic meta-analysis of the efficacy and heterogeneity of disease management programs in congestive heart failure

BackgroundWe sought to systematically combine the evidence on efficacy of disease management programs (DMPs) in the treatment of congestive heart failure (CHF), to identify and explain heterogeneity of results from prior studies of DMPs, and to assess potential publication bias from these studies.Methods and ResultsWe conducted a systematic literature search on randomized clinical trials investigating the effect of DMPs on CHF outcomes and performed meta-analyses and meta-regressions comparing DMPs and standard care for mortality and rehospitalization. We included 36 studies from 13 different countries (with data from 8341 patients). Our meta-analysis yielded a pooled risk difference of 3% (95% confidence interval [CI] 1–6%, P < .01) for mortality and of 8% (95% CI 5–11%, P < .0001) for rehospitalization, both favoring DMP. Factors explaining heterogeneity between studies included severity of disease, proportion of β-blocker at baseline, country, duration of follow-up, and mode of postdischarge contact. No statistically significant publication bias was detected.ConclusionDMPs have the potential to reduce morbidity and mortality for patients with CHF. The benefit of the intervention depends on age, severity of disease, guideline-based treatment at baseline, and DMP modalities. Future studies should directly compare the effect of different aspects of disease management programs for different populations.     

Mesenteric vasculitis causing ileocecal intussusception as the initial presentation of systemic lupus erythematosus: a case report

Mesenteric vasculitis is one of the most devastating complications of systemic lupus erythematosus (SLE) and may produce a spectrum of complications, including ulceration, hemorrhage, bowel necrosis, perforation, serositis, and ascites. Intussusception is a process in which a segment of intestine invaginates into the adjoining intestinal lumen, causing bowel obstruction. Intussusception in association with SLE has rarely been reported. Here we report a case of SLE whose initial presentation was mesenteric vasculitis causing ileocecal intussusception.

     

Association between depression and sleep quality in patients with systemic lupus erythematosus: a systematic review and meta-analysis

Background

Currently, there is no consistent understanding of the relationship between depression and sleep quality in patients with systemic lupus erythematosus (SLE). This study aimed to explore the correlation between depression and sleep quality in SLE patients.

Methods

Five English (PubMed, Web of Science, EMBASE, Cochrane Library, and CINAHL) databases were systematically searched from inception to January 12, 2021. Two authors independently screened publications and extracted data according to set inclusion and exclusion criteria. Statistical analyses were performed with STATA 16.0. Data were pooled using a random-effects model.

Results

A total of 9 identified studies matched the inclusion criteria, reporting on 514 patients with SLE in the analysis. A moderate correlation of depression with sleep quality was found (pooled r?=?0.580 [0.473, 0.670]). Compared to good sleepers, patients with SLE and poor sleep quality had higher levels of depression (standardized mean difference?=????1.28 [??1.87,???0.69]). Depression was associated with subjective sleep quality (r?=?0.332 [0.009, 0.592]), sleep latency (r?=?0.412 [0.101, 0.649]), sleep disturbances (r?=?0.405 [0.094, 0.645]), daytime dysfunction (r?=?0.503 [0.214, 0.711]), the four dimensions of Pittsburgh Sleep Quality Index (PSQI), while no significant correlation was found in the other three PSQI dimensions.

Conclusion

Depression had a moderate correlation with sleep quality in patients with SLE. Patients with poor sleep quality tended to have higher level of depression than that of good sleepers. Awareness of the correlation may help rheumatology physicians and nurses to assess and prevent depression and improve sleep quality in patients with SLE.

     

Evaluation of the alternative classification criteria of systemic lupus erythematosus established by Systemic Lupus International Collaborating Clinics (SLICC)

Objective: To evaluate the performance of the 2012 Systemic Lupus International Collaborating Clinics criteria (SLICC-12) on classifying systemic lupus erythematosus (SLE) in an uncontrolled multi-centered study with real-life scenario of the patients in Japan.

Methods: This study comprised 495 patients with SLE or non-SLE rheumatic diseases and allied conditions from 12 institutes in Japan. Chart review of each patient was performed by the 27 expert rheumatologists and diagnosis of 487 cases reached to the consensus. Value of the SLICC-12 on SLE classification was analyzed comparing with the 1997 revised American College of Rheumatology SLE classification criteria (ACR-97) employing the expert-consented diagnoses.

Results: Compared to the ACR-97, the SLICC-12 had a higher sensitivity (ACR-97 vs. SLICC-12: 0.88 vs. 0.99, p?Conclusion: Although employment of SLICC-12 for the classification for SLE should be carefully considered, the SLICC-12 showed the higher sensitivity on classifying SLE in Japanese population.     

Clinical significance of plasma presepsin levels in patients with systemic lupus erythematosus

Objectives: Presepsin (PSEP: soluble CD14 subtype) is produced from bacteria-stimulated monocytes or neutrophils, thus recognized as a biomarker of sepsis. Aberrant functions in monocyte or neutrophils are increasingly recognized in systemic lupus erythematosus (SLE). We investigated whether plasma PSEP reflects disease activity in patients with SLE.

Methods: This retrospective study comprised 35 patients with SLE and 72 with non-SLE autoimmune diseases who visited our facility during the period from August 2012 to September 2015. Plasma PSEP levels and laboratory data were compared between SLE and non-SLE. Clinical markers of SLE disease activity, including SLE disease activity index 2000 (SLEDAI-2K), serum complement concentrations and serum anti-ds-DNA antibodies were assessed in correlation with plasma PSEP levels.

Results: Plasma PSEP levels in SLE were higher than those in non-SLE. This phenomenon holds true when comparing SLE and non-SLE patients in the absence of infection (p?=?.0008). Plasma PSEP levels in SLE patients negatively correlated with C3 (r =?–0.4454, p =?.0430), CH50 (r =?–0.4502, p =?.0406) and positively with SLEDAI-2K (r =?0.4801, p =?.0237).

Conclusion: Elevated plasma PSEP levels were correlated with disease activity of SLE, suggesting inappropriate monocyte or neutrophil activation in the pathophysiology of SLE exacerbation.     

Multicenter double-blind randomized controlled trial to evaluate the effectiveness and safety of bortezomib as a treatment for refractory systemic lupus erythematosus

Abstract

Objectives: The objective of this study is to evaluate the efficacy and safety of bortezomib for treating systemic lupus erythematosus (SLE), in patients whose disease activity could not be controlled.

Methods: Fourteen SLE patients with persistent disease activity were selected, who required prednisolone doses of >10?mg/d despite concomitant immunosuppressive therapy. Patients were randomly administered either bortezomib or a placebo, eight times. The primary and secondary end-points were a change in anti-dsDNA antibody titer at week 24 and the SLE Responder Index (SRI), respectively.

Results: In the bortezomib group, four out of eight patients discontinued the trial; three others failed to complete the minimum protocol treatment due to adverse reactions. The changes in anti-dsDNA antibody titers at week 24 were 4.24% and ?1.96%, for the bortezomib and placebo groups, respectively, disconfirming bortezomib’s efficacy. In contrast, the corresponding SRI at week 12 was 75% and 40%.

Conclusions: As bortezomib therapy for SLE is associated with many adverse reactions, treatment indications should be selected carefully, and protocols should aim to prevent these occurrences. Although the change in anti-dsDNA antibody titer did not support the efficacy of bortezomib as a treatment for SLE, high SRI in the treatment group suggests bortezomib may utilize mechanisms other than inhibition of anti-dsDNA antibody production.