Serum Growth Arrest-Specific Protein 6 Levels are a Reliable Biomarker of Disease Activity in Systemic Lupus Erythematosus

Purpose

Growth arrest-specific protein 6 (Gas6) has been suggested to be a biomarker of disease activity in patients with systemic lupus erthematosus (SLE). We investigated the clinical significance of this protein in Korean SLE.

Methods

Blood samples were collected from 150 SLE patients and 50 normal controls (NC). In addition, follow-up samples were collected from 50 SLE patients.

Results

Serum Gas6 levels of SLE patients (43.01?±?28.02 ng/mL) were higher than those of NC (20.15?±?9.23 ng/mL, p?<?0.001). When evaluated sensitivity and specificity of the Gas6 for diagnosing SLE using ROC curves, the sensitivity and specificity were 72.7 % and 84 % with a cut-off value of 25.3 ng/mL. In the ROC analysis of Gas6, anti-dsDNA antibody, ESR, complement 3 and complement 4 to identify patients with active lupus, area under the curve (AUC) of Gas6 was highest with 0.763. Serum Gas6 levels were significantly higher in the patients with serositis (70.04?±?30.85 ng/mL) and renal disorder (65.66 ±32.28 ng/mL) compared to those without (41.88?±?27.44 ng/mL, p?=?0.033, 40.3?±?26.33 ng/mL, p?=?0.001, respectively). Gas6 levels were correlated positively with anti-dsDNA antibody (r?=?0.199, p?=?0.015), ESR (r?=?0.204, p?=?0.013) and SLEDAI (r?=?0.512, p?<?0.001). In addition, serum Gas6 levels were correlated negatively with hemoglobin (r?=??0.165, p?=?0.043), lymphocyte count (r?=??0.165, p?=?0.043), complement 3 (r?=??0.343, p?<?0.001) and complement 4 (r?=??0.316, p?<?0.001). Furthermore, change in serum Gas6 levels was correlated with change in SLEDAI levels in the SLE patients that were followed up (r?=?0.524, p?<?0.001).

Conclusion

These results suggest that serum Gas6 can be a reliable clinical marker for monitoring disease activity and treatment response in SLE.     

Serum Levels of Calreticulin in Correlation with Disease Activity in Patients with Rheumatoid Arthritis

Objective

The aim of our study was to investigate the contribution of serum calreticulin (CRT) in the assessment of disease activity in rheumatoid arthritis (RA).

Methods

Serum CRT levels were measured by ELISA in 70 patients with established RA, 30 systemic lupus erythematosus (SLE), 25 other autoimmune diseases, 20 osteoarthritis (OA), and 35 of healthy controls (HC). Correlations of CRT serum levels with disease activity [Disease Activity Score for 28 joints (DAS28)], erythrocyte sedimentation rate(ESR) and C-reactive protein (CRP) were assessed. Serum CRT levels were also detected in RA patients whose RF, anti-CCP and anti- MCV antibodies were positive and negative.

Results

Serum CRT levels in RA patients (4.817?±?2.425 ng/ml) was significantly higher (P <0.05) compared with those in the serum of OA (3.574?±?0.942 ng/ml), SLE (4.013?±?1.536 ng/ml), other autoimmune diseases (3.882?±?0.837 ng/ml) and HC (3.726?±?0.627 ng/ml). Significant positive correlation of CRT with DAS28, ESR and CRP was found in RA patients. Furthermore, RA patients whose anti-CCP and anti-MCV antibodies were positive had higher levels of CRT (P?<?0.01).

Conclusion

Serum CRT levels were increased in patients with RA compared with those controls. Moreover, a significant correlation was observed between serum CRT levels and disease activity in RA. It might be used as a potential biomarker for clinical diagnosis and provide additional information regarding disease activity along with the traditional indices such as ESR and CRP.     

Assessing vitamin D levels in an anti-DFS70 positive population: New insights emerging

Abstract

Background: Anti-dense fine speckled 70 (DFS70) autoantibodies have more often been described in apparently healthy individuals than in patients with systemic autoimmune rheumatic diseases (SARD). The aim of this study was to explore the link between anti-DFS70 autoantibodies and vitamin D (25(OH)D) levels in an Italian adult cohort.

Methods: Serum samples from 34 (five males and 29 females) anti-DFS70 positive patients (index cases), 34 ANA-negative healthy controls, 34 ANA-positive anti-DFS70 negative SLE patients, both groups age- and gender-matched with the index cases, 23 ANA-positive anti-DFS70 negative healthy blood donors and six female SARD patients showing mixed DFS positive pattern were collected and tested for 25(OH)D levels. Relevant demographics and lifestyle practices, body mass index (BMI), comorbidities, and use of medication were recorded for patients and healthy controls.

Results: Mean serum levels of 25(OH)D were significantly higher in anti-DFS70 positive subjects (mean?±?SD: 22.1?±?9.8?ng/ml) than in ANA-negative healthy controls (mean?±?SD: 17.3?±?6.7?ng/ml; p?=?.03), ANA-positive healthy controls (mean?±?SD: 15.2?±?6.8?ng/ml; p?=?.01), SLE patients (16.6?±?11.0?ng/ml; p?=?.01) and in patients with SARD (15.0?±?5.6?ng/ml; p?=?.01). No statistically relevant differences in BMI, clinical, or demographic parameters were found.

Conclusions: Our findings showed higher levels of vitamin D in anti-DFS70 positive subjects than in the controls, which is compatible with the hypothesis of the “benign” nature of anti-DFS70 antibodies.     

Methylation levels of the TNFA gene are different between Graves’ and Hashimoto’s diseases and influenced by the TNFA polymorphism

Graves’ disease (GD) and Hashimoto’s disease (HD) are different pathological types of autoimmune thyroid diseases (AITDs). However, the epigenetic differences between these diseases have not been elucidated. DNA methylation is one of the primary epigenetic modifications that reflect environmental influences on gene expression. In this study, we evaluated the methylation status of six CpG sites in the TNFA promoter using pyrosequencing and analyzed the data in combination with functional polymorphisms (?1031?T/C and?+123?C/T) in the TNFA gene to clarify the role of gene methylation on the prognosis of AITDs. We examined the methylation pattern in 52 patients with GD, 60 patients with HD, and 29 healthy controls by pyrosequencing. Additionally, we also genotyped the polymorphisms from 163 patients with GD, 152 patients with HD, and 94 healthy controls using the restriction fragment length polymorphism (RFLP) method. Each proportion of subjects with low methylation of the ?72 CpG site (≤11.9%), low methylation of the ?49 CpG site (≤15.5%), and low methylation of the ?38 CpG site (≤8.9%) was significantly increased in the groups with high concentration of TNF-α (≥0.134?pg/mL). The methylation level of the ?72 CpG site was significantly higher in GD cases (10.7?±?4.9%) than in healthy controls (6.8?±?3.9%). The methylation level of the ?49 and ?38 CpG sites were significantly higher in patients with GD in remission (20.5?±?9.5%, 17.6?±?8.0%, respectively) than in healthy controls (13.0?±?7.6%, 7.9?±?7.3%, respectively). The frequency of the TNFA???1031C carrier (CT?+?CC) is correlated with higher TNF-α production and was significantly higher in GD (35.0%) and HD (39.5%) cases than in controls (19.1%). In the subjects with the TNFA???1031C carrier (CT?+?CC), the methylation level of the ?72 CpG site was significantly higher in GD (11.5?±?5.7%) than in HD (6.0?±?3.4%). However, there was no difference between GD and HD in patients with the TT genotype. Cumulatively, our data indicate the methylation levels of CpG sites in the TNFA gene may be related to the difference between GD and HD in AITDs and may be influenced by the TNFA gene polymorphism.     

Serum Leptin Levels,Leptin Receptor Gene (LEPR) Polymorphism,and the Risk of Systemic Lupus Erythematosus in Kashmiri Population

The study is conducted to evaluate relationship between LEPRQ223R (Gln?>?Arg) polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG?+?GG) in cases compared to controls [OR?=?2.52, CI?=?1.18–5.35, p?=?0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR?=?1.49, p?=?0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR?=?11.8, CI?=?1.6–85.1, p?=?0.002] and an inverse association with cardiac disorder [OR?=?0.09, CI?=?0.02–0.46, p?=?0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9?±?19.5 vs 14.8?±?10.4, p?<?0.001). SLE patients in the highest quartile leptin levels (≥32.5?ng/mL) were significantly more likely to have higher BMI (p?=?0.001) and increased risk of developing arthritis (p?=?0.02). Furthermore positive association was observed between the variant genotype(AG?+?GG) and leptin levels (p?=?0.001) in SLE patients. Thus, it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.     

Validation of photoplethysmography as a method to detect heart rate during rest and exercise

Abstract

Despite their enhanced marketplace visibility, validity of wearable photoplethysmographic heart rate monitoring is scarce. Forty-seven healthy participants performed seven, 6-min exercise bouts and completed a valid skin type scale. Participants wore an Omron HR500U (OHR) and a Mio Alpha (MA), two commercial wearable photoplethysmographic heart rate monitors. Data were compared to a Polar RS800CX (PRS). Means and error were calculated between devices using minutes 2–5. Compared to PRS, MA data was significantly different in walking, biking (2.41?±?3.99?bpm and 3.26?±?11.38?bpm, p?<?0.05) and weight lifting (23.30?±?31.94?bpm, p?<?0.01). OHR differed from PRS in walking (4.95?±?7.53?bpm, p?<?0.05) and weight lifting (4.67?±?8.95?bpm, p?<?0.05). MA during elliptical, stair climbing and biking conditions demonstrated a strong correlation between jogging speed and error (r?=?0.55, p?<?0.0001), and showed differences in participants with less photosensitive skin.     

Decreased proportions of CD4 + IL17+/CD4 + CD25 + CD127− and CD4 + IL17+/CD4 + CD25 + CD127 − FoxP3+ T cells in children with autoimmune thyroid diseases*

Until now, altered balance of Th1 and Th2 immune cells has been postulated to play an important role in the pathogenesis of autoimmune thyroid diseases (AITD). However, recent studies on thyroid diseases have suggested a new role for Th17 cells that have been classified as a new lineage, distinct from Th1, Th2 and Treg cells. Despite wide interest, the role of Th17 cells in the pathogenesis of inflammatory and autoimmune diseases is still debated. The aim of the study was to estimate the proportions of Th17/Treg T cells in peripheral blood from patients with Graves’ disease (GD; n?=?29, mean age 15.4?±?5.1 years), Hashimoto’s thyroiditis (HT; n?=?39, mean age 15.2?±?4.1 years) and in healthy controls (n?=?49, mean age 14.8?±?3 years). Polychromatic flow cytometry and several fluorochrome-conjugated monoclonal antibodies were applied to delineate Th17 and Treg cells. The analysis of Th17/Treg T cell proportions in peripheral blood from patients with Graves’ disease revealed significantly lower ratios of CD4?+?IL17+/CD4?+?CD25?+?CD127???(p?p?p?p?R?=?0.71, p?R?=?0.72, p?R?=?0.66, p?相似文献   

Computerized acoustic cardiography correlates with echocardiography and invasive haemodynamics after percutaneous transvenous mitral commissurotomy

Background:?Rheumatic mitral stenosis severity has been assessed by the systolic time interval between the QRS onset and the first heart sound (QS1) by phonocardiography. We hypothesized that non-invasive computerized acoustic cardiography could evaluate mitral stenosis severity compared with echocardiography and invasive haemodynamics in patients undergoing percutaneous transvenous mitral commissurotomy (PTMC).

Methods:?27 patients underwent computerized acoustic cardiography, echocardiography, and invasive haemodynamic measurements prior to and after PTMC.

Results:?The mean age was 31?±?10 years, and 21 (78%) were female. By echocardiography, mitral valve area increased from 0.82?±?0.14 to 1.50?±?0.24 cm² (p?<?0.0001). The QS1 interval decreased from 101.7?±?12.9 to 93.2?±?9.2?ms (p?<?0.0001). The change in the QS1 interval correlated with the change in mitral valve area by echocardiography (p?=?0.037), right ventricular systolic pressure (p?<?0.0001), and the invasive mitral valve gradient (p?=?0.076).

Conclusions:?Acoustic cardiography may be used as an adjunctive non-invasive diagnostic tool to assess mitral stenosis severity.     

Rapid response to and long-term effectiveness of anti-CD20 antibody in conventional therapy resistant Graves’ orbitopathy: A five-year follow-up study

Abstract

The aim of this investigations was to study the effectiveness of anti-CD20 antibody therapy in Graves’ orbitopathy (GO) resistant to glucocorticoids. Five patients were entered in the study. The protocol required no improvement of orbital status after a recent course of glucocorticoids. Activity of GO was confirmed by three independent techniques: clinical activity score (CAS), ^99mTc-labeled diethylene triamine pentaacetic acid (^99mTc DTPA) single photon emission computed tomography and magnetic resonance imaging. Rituximab (RTX) was given as weekly infusions of 375?mg/m² body surface area for four weeks. The mean follow-up period was 67 (range 58–81) months. Improvement of GO has been observed in all patients: CAS before therapy was 6.5?±?1.7 and decreased to 3.4?±?1.6 by one month (p?<?0.05) and remained unchanged (3.2?±?1.7) at 12 months. No further CAS change, in either direction, was detected during the yearly follow-up visits. The mean DTPA uptake before therapy was 16.52?±?4.51?MBq/cm³ and decreased to 11.97?±?2.36?MBq/cm³ at one year (p?<?0.002). The mean of T2 relaxation times before and one year after therapy were 96.91?±?17.61?ms and 84.29?±?9.41?ms, respectively (p?<?0.001). The mean serum TSH receptor antibody (TRAb) levels before therapy, at the one month and one year control visits were 7.4?±?3.4?U/L, 5.6?±?4.5?U/L and 1.7?±?1.5?U/L, respectively (p?<?0.004). No correlation between changes of TRAb and activity parameters has been found. Anti-CD20 treatment seems to influence positively the clinical course of GO, and this effect seems to be stable for five years. To our knowledge, this is the longest published follow-up of RTX treatment in GO.     

Serum Soluble Triggering Receptor on Myeloid Cells-1 (sTREM-1) is Elevated in Systemic Lupus Erythematosus but does not Distinguish Between Lupus Alone and Concurrent Infection

We sought to determine serum triggering receptor expressed on myeloid cell-1 (sTREM-1) level in a cohort of patients with systemic lupus erythematosus (SLE). Serum sTREM-1 level of 98 patients with SLE and 49 healthy controls was assayed by ELISA. Serum sTREM-1 level was significantly elevated in a cohort of 78 unselected consecutively recruited patients with SLE (mean 1.1?±?2.8 ρg/ml, median 0.02 ρg/ml) compared to that of the controls (mean 0.11?±?0.3 ρg/ml, median 0 ρg/ml; p?<?0.0001). We also determined serum sTREM-1 level of 20 SLE patients with a concurrent infection (mean 0.6?±?1.1 ρg/ml, median 0.12 ρg/ml) and found it not statistically significant compared with that of the patients without infection. Serum sTREM-1 level did not correlate with SLE disease activity. Our finding of elevated serum sTREM-1 level suggests an increased shedding of TREM-1 in SLE and a possible novel pathway of innate immune response in autoimmunity.     

Effects of diphencyprone on expression of Bcl-2 protein in patients with Alopecia areata

Background: Alopecia areata (AA) development is attributed to a T cell involved autoimmune process. Apoptosis is one of the suspected culprits in pathogenesis of this disorder. This disorder can be treated by contact sensitizers like diphencyprone (DPCP). We investigated the effects of treatment with DPCP on the expression of Bcl-2 protein in hair follicle epithelial cells of AA patients and its relation to clinical response to treatment.

Materials and Methods: Patients with chronic and extensive AA who had not received any treatment for at least 6 months were included. Furthermore, 3-mm punch biopsies were obtained from the affected areas before starting the treatment, and, six months after DPCP application, punch biopsies of the same size were taken from the following groups of patients: Group 1: six patients with complete hair regrowth, Group 2: six patients with partial regrowth, and Group 3: six patients with no regrowth. The samples were studied by immunohistochemistry to detect and compare the rate of Bcl-2 expression.

Results: Level of Bcl-2 expression in respondent patients (Group 1) was significantly higher after DPCP treatment (36.50?±?4.23) compared to pretreatment state (3.67?±?1.406, P?<?0.001). Similar finding was observed in second group with partial regrowth (17.67?±?1.745 versus 5.33?±?2.076, P?<?0.01). Such significant change was not observed in third group (4.75?±?1.315 versus 3.50?±?0.645, P?>?0.05).

Conclusion:The results of this study indicate the positive effect of DPCP on regulation (inhibition) of apoptotic process in patients with AA.     

A study on the antioxidant defense system of psoriasis patients in the ethnic population of Kashmir-India

The study was designed to evaluate the role of antioxidant defense system in the etiology of psoriasis, a chronic skin disorder of complex etiology and pathology. Hospital-based case–control study was carried out in major referral hospital in Kashmir, North India. Cases (N?=?40) were composed of patients with psoriasis vulgaris, and controls (N?=?20) were healthy volunteers. Study included estimation in plasma of both patients and controls of glutathione (GSH) levels, superoxide dismutase (SOD) activity, and total antioxidant potential (AOP) as indices of antioxidant defense system and malondialdehyde (MDA) as a measure of lipid peroxidation (LP), an indicator of oxidative stress. The GSH levels, SOD activity, AOP, and malondialdehyde levels in plasma of psoriasis patients were 2.58?±?0.22 μM/l, 5.24?±?0.69 U/ml, 0.020?±?.011?nmol^?1/ml?h, and 0.88?±?0.20 nmol/ml and were 4.76?±?0.52 μM/l, 4.14?±?0.56U/ml, 0.042?±?0.018 nmol^?1/ml?h, and 0.53?±?0.16 nmol/ml in healthy voluntary controls, respectively. A significant decrease in GSH levels (p?<?0.005) and AOP (p?<?0.005) and significant increase in SOD activity (p?<?0.01) MDA levels (p?<?0.005) as an indicator of LP was observed.     

Evaluation of mortality,disease activity,treatment, clinical and immunological features of adult and late onset systemic Lupus erythematosus

Abstract

Objectives: We retrospectively compared disease activity, treatment, clinical and laboratory features, and rate of mortality of 535 SLE patients with adult and late disease onset.

Methods: patients were divided into two groups based on the onset of the disease before or after 50 years of age. Clinical data were collected from medical reports. Disease activity was measured by ECLAM score. Parameters were compared by χ²-test, Fisher’s test, Student’s t or the Mann–Whitney test.

Results: Forty patients (7.5%) were included in the late SLE onset group (group A), while 495 (92.5%) in the adult SLE onset group (group B). Sicca symptoms were more frequent in group A (p?<?0.0008), while glomerulonephritis (p?<?0.0069), reduced C3 (p?<?0.0006) and low C3 (p?<?0.00002) and C4 levels (p?<?0.0006) were more prevalent in group B. Twenty-two deaths (4.3%) were recorded: 14 (2.8%) in group B and 8 (20%) in group A. Deaths were mainly due to infections in group B (28.5%) and cardiovascular events in group A (50%). A lower use of HCQ and LDA were recorded in deceased versus living patients (p?<?0.0001 and 0.0166, respectively), while a higher ECLAM score was measured at onset in dead versus living patients (p?<?0.048).

Conclusions: Late onset SLE occurred in 7.5% of patients and it was associated with sicca symptoms. The use of HCQ and LDA is positively correlated with survival. Death in late onset SLE occurred more frequently for cardiovascular involvement. Higher disease activity at onset of the disease might represent a poor prognostic factor for death in adult onset.     

The absence of physiological neonatal weight loss on the 1st–5th day is associated with decreased later physical indices

Abstract

Aim: To investigate associations between physiological neonatal weight loss on the 1st–5th day and physical indices from birth up to the age of 17 years.

Methods: Data were derived from the personal health records of healthy, full-term and breastfed children born in Vilnius in 1990 and 1996. Five hundred and thirty children (289 boys and 241 girls) who left a maternity unit on the 1st–5th day after birth were included in the analysis.

Results: Infants left the maternity unit on day 4.62?±?2.33. On the day of leaving a maternity unit, infants lost 105.06?±?130.48 g (2.85?±?3.65%) of birth weight. Girls who did not lose or gained weight after birth had already weighed less at birth (3163?±?547 and 3490?±?403 g, respectively, p?<?0.01) and remained lighter up to the age of 17 years (54.3?±?8.7 and 60.8?±?10.1?kg at the age of 17 years respectively, p?<?0.001). Girls who did not lose or gained weight after birth were also shorter than those who lost weight (164.3?±?5.7 and 168.6?±?5.4?cm at the age of 17 years, respectively, p?<?0.001).

Conclusion: Girls who did not lose or gained weight immediately after birth tended to remain shorter and lighter during childhood and adolescence. Only a few statistically significant differences were obtained in boys.     

Body Image in Patients with Systemic Lupus Erythematosus

Background

Systemic lupus erythematosus (SLE), a multisystemic disease of young women may be disfiguring and affect physical and emotional health. Body image literature in SLE is scant and controversial.

Purpose

We compared body image-related quality of life in subjects with (n?=?87) and without (n?=?78) SLE and determined its correlates using the body image quality of life inventory (BIQLI).

Method

The tool was self-administered to consenting individuals. Demographic information along with disease activity and damage assessments for SLE patients were obtained. T test, chi square test, correlational, and regression analyses were used to make comparisons.

Results

Mean age (±SD) were 42.4?±?13.1 and 38.7?±?13.2?years for SLE and non-SLE subjects, respectively. Mean (±SD) BIQLI scores were significantly worse in SLE than non-SLE subjects: 19.9?±?33.2 and 41.6?±?24.8 (p?=?0.001). In SLE, BIQLI scores correlated inversely with overall damage, irreversible cutaneous damage, alopecia, and self-reported depression, and directly with age and health status.

Conclusion

Body image in SLE is poor, and effective interventions may be directed at cutaneous disease activity, damage, and depression.     

The −675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus,its clinical manifestations,and comorbidities in Mexican-Mestizo population

Abstract

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the ?675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the ?675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The ?675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81–3.87; p?<?.001) and 4G/4G (OR = 2.70; CI 1.62–4.51; p?<?.001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31–2.03; p?<?.001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84–3.84; p?<?.001). The 4G/5G genotype was associated with shorter disease duration (p?=?.039), as well as lower levels of haemoglobin (p?=?.001) and haematocrit (p?=?.009); the need for prednisone treatment (p?=?.001), higher BMI (p?=?.03), presence of type 2?DM (p?=?.015), clinical activity (Mex-SLEDAI = 57%; p?=?.047), Chronicity (SLICC-ACR = 0; p?=?.015) and CRP levels (p?=?.015) were associated with 5G/5G genotypes. In conclusion, the ?675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.