Increase in ventricular-arterial stiffness in patients with psoriatic arthritis.

OBJECTIVES: Ventricular and arterial stiffness is an accepted cause of myocardial diastolic dysfunction. The aim of this study is to determine whether there is increased ventricular and arterial stiffness in patients with PsA and any relationship with disease-related risk factors. METHODS: Seventy-three patients with PsA were divided into two subgroups based on the absence or presence of hypertension and/or left ventricular (LV) hypertrophy. Fifty healthy controls were enrolled for comparison. All participants underwent non-invasive assessments including conventional echocardiography with tissue Doppler imaging and pulse wave analysis. Ventricular stiffness was measured by ventricular end-systolic and diastolic elastance, whereas arterial stiffness was measured by total arterial compliance and aortic augmentation index. RESULTS: There was significantly increased ventricular and arterial stiffness in patients with PsA (P < 0.001), even in those without hypertension and/or LV hypertrophy. Based on the cut-off points derived from the controls, 38.4% of PsA patients had increased LV stiffness including 31.5% in diastole and 17.8% in systole, and 15.1% had increased arterial stiffness. Multivariable logistic regression analysis showed that long PsA disease duration (>10 years) (odds ratio = 6.55, P = 0.001) was an independent risk factor for increased LV diastolic elastance after adjusting for age, gender and hypertension. CONCLUSION: Patients with PsA may have increased ventricular and arterial stiffness even without evidence of LV remodelling, and those with long disease duration may be at a higher risk. Therefore, prolonged inflammatory burden may be an important cause of early cardiovascular disease in patients with PsA.

Glomerular and tubulointerstitial miR-638, miR-198 and miR-146a expression in lupus nephritis.

AIM: MicroRNAs (miRNAs) play important roles in the pathogenesis of autoimmune diseases. We studied the intra-renal expression of miRNA targets that were reported to be differentially expressed in peripheral blood or urine between lupus nephritis (LN) patients and normal controls. METHODS: We quantified the expression of in glomerulus and tubulointerstitium of miR-146a, miR-155, miR-198 miR-638 and miR-663 in 42 patients with LN and 10 healthy controls. RESULTS: As compared with controls, LN patients had lower glomerular expression of miR-638 (P < 0.001) but higher tubulointerstitial expression of this target (P = 0.001). Both glomerular and tubulointerstitial expression of miR-198 were higher in LN patients than controls (P < 0.001). For miR-146a, LN patients only had higher expression in glomerulus (P = 0.005) but not in tubulointerstitium. Tubulointerstitial miR-638 expression was significantly correlated with proteinuria (r = 0.404; P = 0.022) and disease activity score (r = 0.454; P = 0.008), while glomerular miR-146a expressions were correlated with estimated GFR (r = 0.453; P = 0.028) and histological activity index (r = 0.494; P = 0.027). CONCLUSION: We found that intra-renal expression of miR-638, miR-198 and miR-146a are differentially expressed between LN patients and normal controls. Furthermore, the degree of change in glomerular miR-146a and tubulointerstitial miR-638 expression correlated with clinical disease severity. The results suggested that these miRNA targets may play a role in the pathogenesis of lupus nephritis.

Repeat renal biopsy in lupus nephritis: a change in histological pattern is common.

BACKGROUND: The role of longitudinal change in sequential renal biopsies of lupus nephritis (LN) patient remains elusive. METHODS: Clinical and pathological documents of 156 LN patients with repeat renal biopsies (412 times) were collected from a database. RESULTS: The percent of transformation of the biopsy class from reference biopsies to repeat biopsies was 75%. For the reference biopsies that showed pure proliferative, pure membranous, and mixed nephritis, the histological pattern in the repeat biopsies changed in 57.8, 50.0, and 60.4%, respectively. As compared to reference biopsy, repeat biopsy had a higher degree of tubulointerstitial scarring (p < 0.001), chronicity index (p < 0.001) and serum creatinine (p < 0.001). In addition, baseline serum creatinine was significantly lower (p = 0.004), and the time lapse between the two biopsies was significantly longer (p < 0.001) amongst patients who had a change in the histological pattern upon repeat renal biopsy than those whose histological pattern remained the same. CONCLUSION: The present study suggests that a change in the histological class of LN is common in systemic lupus erythematosus patients with lupus flare, and the histology during disease flare could not be predicted by baseline clinical, biochemical, or pathological parameters. Our results indicate that when there is lupus flare with renal involvement, repeat renal biopsy is often necessary to guide the treatment.

Gene expression of TWEAK/Fn14 and IP-10/CXCR3 in glomerulus and tubulointerstitium of patients with lupus nephritis.

AIM: The role of the tumour necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 and interferon-inducible protein (IP-10)/CXCR3 axis in the pathogenesis of lupus nephritis were studied. METHODS: The mRNA expression of TWEAK, Fn14, IP-10 and CXCR3 were quantified in the glomerulus and tubulointerstitium of 42 patients with lupus nephritis (LN group) and 10 healthy controls. RESULTS: As compared to controls, LN patients had higher glomerular expression of TWEAK and Fn14, but glomerular CXCR3 expression was lower in the LN group. Similarly, the LN group had higher tubulointerstitial expression of TWEAK and Fn14, but lower tubulointerstitial expression of CXCR3, than controls. Glomerular TWEAK expression of class V nephritis was significantly higher than class IV nephritis. Glomerular expression of CXCR3 significantly correlated with proteinuria (r = -0.532; P = 0.019), whereas tubulointerstitial CXCR3 significantly correlated with serum creatinine (r = -0.447; P = 0.029). CONCLUSION: In patients with lupus nephritis, there is an increase in intra-renal expression of TWEAK and Fn14, and a decrease in CXCR3 expression. Intra-renal expression of CXCR3 correlates with proteinuria and renal function. Our findings suggest that the TWEAK/Fn14 and IP-10/CXCR3 axis may contribute to the pathogenesis of lupus nephritis.

Testing scaling assumptions, reliability and validity of medical outcomes study short-form 36 health survey in psoriatic arthritis.

OBJECTIVES: The Medical Outcome Survey short-form 36 (SF-36) is widely used in studies of PsA. We test the fundamental scaling assumptions for the validity of SF-36 eight scales and two summary scores in PsA. METHODS: We tested the five scaling criteria according to the International Quality of Life Assessment project and the validity of the physical component summary (PCS) and mental component summary (MCS) scores. The construct validity for SF-36 in PsA was evaluated. RESULTS: A total of 168 PsA subjects according to CASPAR criteria (46.4% females) with SF-36 data were analysed. The mean (S.D.) age and duration of illness were 47.7 (11.9) and 8.4 (7.3) years. PsA subjects had poorer quality of life as compared with normal population. The norm-based mean (S.D.) PCS and MCS were 31.6 (14.2) and 45.2 (12.7), respectively. The Pearson's correlations between an item and its hypothesized scale were all >0.4, indicating item internal consistency. All item-own scale correlations exceed item-other scale correlations, except minor scaling failure in general health. The Cronbach's alpha-coefficients of internal reliability (Cronbach's alpha) were all above the standard value of 0.7, indicating a unique concept in each scale. Principal component analysis explained 69.4 and 73.7-99.9% of the total variance and total reliable variance in all SF-36 scales. The two-factor model is supported. CONCLUSIONS: PsA had high impact on quality of life. All eight scales and two summary scores of SF-36 satisfied criteria for scaling assumption. SF-36 is a valid measurement for quality of life in PsA. The reporting of PCS and MCS in PsA is supported.

The gene expression of type 17 T-helper cell-related cytokines in the urinary sediment of patients with systemic lupus erythematosus.

OBJECTIVE: We studied the role of type 17 Th cells (TH17) in the pathogenesis of SLE. METHODS: We quantified the mRNA expression of IL-17, -23, -27 and retinoic-acid-related orphan receptor (ROR)-gamma, the regulator for the development and function of TH17, in the urinary sediment of 23 subjects with active lupus nephritis, 25 subjects with a history of lupus nephritis in remission, 30 SLE patients with no history of renal involvement and 8 healthy subjects. RESULTS: All three groups of lupus patients had a higher urinary expression of TH17-related cytokines than the controls. However, urinary expression of IL-17 and -27 was found to be inversely correlated with the SLEDAI score (r = -0.252 and -0.258, respectively; P < 0.05 for both). For patients with active lupus nephritis, the histological activity index of kidney biopsy was also found to be inversely correlated with the urinary expression of ROR-gamma (r = -0.447; P = 0.032), IL-17 (r = -0.454; P = 0.029) and IL-23 (r = -0.455; P = 0.029). Urinary expression of IL-17, -23, -27 and ROR was also found to be inversely correlated with the urinary expression of IFN-gamma and T-bet, the key transcription factor of type 1 Th cells. After 6 months of treatment, urinary IL-27 expression rose significantly in patients with complete response (from 2.07 +/- 1.62 to 3.70 +/- 1.69; P = 0.028) but remained unchanged in those with partial or no response (from 2.60 +/- 1.87 to 2.52 +/- 1.94; P = 0.9). CONCLUSIONS: The urinary expression of TH17-related genes is increased in SLE patients. The degree of up-regulation, however, is inversely related to systemic and renal lupus activity, as well as urinary expression of TH1-related genes. Urinary expression of TH17-related genes increased again after successful immunosuppressive treatment of active disease. Our findings suggest a regulatory role of TH17-related cytokines in pathogenesis of lupus nephritis.

Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity.

IL-23-dependent IL-17-producing T helper (Th) lymphocytes are associated with autoimmunity. We investigated the immunopathological mechanisms for activation of Th17 cells of patients with systemic lupus erythematosus (SLE). Concentration of cytokines/chemokine in plasma and culture supernatant from SLE patients and healthy controls were measured by ELISA or flow cytometry. Plasma IL-12, IL-17, IL-23 and CXCL10 concentrations and the number of Th17 cells were significantly elevated in SLE patients than control subjects (both p<0.05). Elevated IL-12, IL-17 and CXCL10 concentrations correlated positively and significantly with SLEDAI (all p<0.05). Plasma IL-12 and IL-17 showed significant and positive correlation with plasma Th1 chemokine CXCL10 concentration in SLE patients (all p<0.05). Ex vivo inductions of IL-17 by IL-23 or IL-18 from co-stimulated lymphocytes were significantly higher in SLE patients than controls (all p<0.05). The activated IL-23/IL-17 axis is important for the inflammatory immunity in SLE.

Analgesic and anti-arthritic effects of Lingzhi and San Miao San supplementation in a rat model of arthritis induced by Freund's complete adjuvant.

AIM OF STUDY: In this study, we have investigated the analgesic and anti-arthritic effects of a traditional Chinese medicine (TCM) combination of Lingzhi and San Miao San (SMS) in a rat model of arthritis induced by Freund's complete adjuvant (FCA). MATERIALS AND METHODS: Sprague-Dawley rats were induced with monoarthritis by single unilateral injection of FCA into the knee joint. The TCM combination was administered to the rats daily by intraperitoneal injection (50mg/(kgday)) or via oral administration (500mg/(kgday)) for 7 days before induction of arthritis and 7 days after. Extension angle that provoked struggling behavior, and size and blood flow of the rat knees were measured to give indexes of allodynia, edema, and hyperemia, respectively. The extent of cell infiltration, tissue proliferation, and erosions of joint cartilage provided additional indexes of the arthritis condition. RESULTS: FCA injection produced significant allodynia, edema, hyperemia, immune cell infiltration, synovial tissue proliferation, and erosions of joint cartilage in the ipsilateral knees compared with the contralateral saline-injected knees. Intraperitoneal injection of the TCM combination (50mg/(kgday)) suppressed allodynia, edema, and hyperemia in the inflamed knees, and oral administration (500mg/(kgday)) suppressed edema and hyperemia. Histological examination showed that the TCM administered by either route reduced immune cell infiltration and erosion of joint cartilage. CONCLUSIONS: These findings suggest the Lingzhi and SMS formulation has analgesic and anti-inflammatory effects in arthritic rat knees, and concur to previous clinical studies that showed the TCM combination reduced pain in rheumatoid arthritis patients, and extends its possible benefit to suppression of inflammatory symptoms in these patients.

Effect of Treat-to-target Strategies Aiming at Remission of Arterial Stiffness in Early Rheumatoid Arthritis: A Randomized Controlled Study.

OBJECTIVE: To determine the efficacy of 2 tight control treatment strategies aiming at Simplified Disease Activity Score (SDAI) remission (SDAI ≤ 3.3) compared to 28-joint count Disease Activity Score (DAS28) remission (DAS28 < 2.6) in the prevention of arterial stiffness in patients with early rheumatoid arthritis (RA). METHODS: This was an open-label study in which 120 patients with early RA were randomized to receive 1 year of tight control treatment. Group 1 (n = 60) aimed to achieve SDAI ≤ 3.3 and Group 2 (n = 60), DAS28 < 2.6. Pulse wave velocity (PWV) and augmentation index (AIx) were measured at baseline and 12 months. A posthoc analysis was also performed to ascertain whether achieving sustained remission could prevent progression in arterial stiffness. RESULTS: The proportions of patients receiving methotrexate monotherapy were significantly lower in Group 1 throughout the study period. At 12 months, the proportions of patients achieving DAS28 and SDAI remission, and the change in PWV and AIx, were comparable between the 2 groups. In view of the lack of differences between the 2 groups, a posthoc analysis was performed at Month 12, including all 110 patients with PWV, to elucidate the independent predictors associated with the change in PWV. Multivariate analysis revealed that achieving sustained DAS28 remission at months 6, 9, and 12 and a shorter disease duration were independent explanatory variables associated with less progression of PWV. CONCLUSION: With limited access to biologic disease-modifying antirheumatic drugs, treatment efforts toward DAS28 and SDAI remission had similar effects in preventing the progression of arterial stiffness at 1 year. However, achieving sustained DAS28 remission was associated with a significantly greater improvement in PWV. [Clinical Trial registration: Clinicaltrial.gov NCT01768923.].

Impaired left ventricular apical rotation is associated with disease activity of psoriatic arthritis.

OBJECTIVE: Although early cardiovascular (CV) involvement has been found in patients with psoriatic arthritis (PsA), few studies have related this to PsA disease activity. The aim of our study was to evaluate left ventricular (LV) mechanics using novel, more sensitive techniques based on assessment of LV rotation for the detection of impaired LV function in patients with PsA correlated with disease-related risk factors. METHODS: Seventy-six patients with PsA and 24 healthy control subjects were enrolled, including 33 patients without any CV risk factors. All participants underwent conventional echocardiography and 2-dimensional speckle tracking imaging. Global longitudinal, apical circumferential, and radial strain, and apical rotation and maximal untwisting rate during early diastole were measured. RESULTS: Although patients with PsA had normal LV ejection fraction, the myocardial deformation in multidimensional planes was impaired. Based on the cutoff point derived from the apical rotation of control subjects, 81% of the patients had subclinical systolic and/or diastolic dysfunction. Similar prevalence was found in patients without CV risk factors. Spearman correlation demonstrated a relationship between Disease Activity Score in 28 joints (r=0.299, p=0.011), erythrocyte sedimentation rate (r=0.309, p=0.008), and impaired apical rotation, even after adjusting for age and hypertension. No correlation was found between longitudinal, radial, and circumferential strain and disease activity. CONCLUSION: Subclinical impaired myocardial deformation was common in patients with PsA even without CV risk factors. Apical rotation was associated with the status of PsA disease activity. These new speckle tracking echocardiography techniques can detect subclinical myocardial involvement in PsA.

Construct validity of the modified numeric rating scale of patient global assessment in psoriatic arthritis.

OBJECTIVE: The construct validity of the patient global health assessment (PGA) in psoriatic arthritis (PsA) has not been analyzed, despite its common use. We evaluated the construct validity of a numeric rating scale (NRS) of the PGA in PsA. METHODS: Patients with PsA who fulfilled the ClASsification for Psoriatic ARthritis (CASPAR) criteria were recruited at a tertiary referral center. Demographic data were collected and PGA data were determined from administration of an 11-point NRS (0 to 10 points representing best to worst status). Convergent and discriminant validity were evaluated by correlation between PGA and clinical variables. Patients were grouped as having severe disease based on Disease Activity Score 28-joint count (DAS28) > 5.1, Health Assessment Questionnaire (HAQ) > 1.0, walking with aids, and social welfare-dependent. Patients were grouped as being in remission by DAS28 < 2.6 and the Minimal Disease Activity Criteria. Known-group validity of PGA was evaluated. RESULTS: A total of 125 patients (52% men) were studied. Convergent validity revealed strong correlations of PGA with pain score, HAQ, and DAS28; and weak correlations with skin severity score, physician's global assessment and morning stiffness. In multivariate analysis, PGA was associated with pain, physical function, mental function, and skin severity score. PGA distinguished different levels of severity well, as determined by comparison with different known groups with large effect sizes. CONCLUSION: Judged on an NRS, the PGA had good construct validity and satisfactorily distinguished all levels of severity in PsA.

Expression of miR-146a and miR-155 in the urinary sediment of systemic lupus erythematosus.

We studied the levels of miR-146a and miR-155 in the urine sediment of SLE patients. The levels of miR-146a and miR-155 in the urine sediment of 40 SLE patients who were receiving calcitriol treatment and 13 healthy controls were determined with real-time quantitative polymerase chain reaction. The levels of urinary miR-146a and miR-155 in patients with SLE were significantly higher than that in healthy controls. Calcitriol treatment reduced the levels of urinary miR-155 in patients with SLE. The level of urinary miR-146a significantly correlated with estimated glomerular filtration rate (r = 0.242, P = 0.008). The level of urinary miR-155 significantly correlated with proteinuria (r = 0.407, P < 0.001) and systemic lupus erythematosus disease activity index (r = 0.278, P = 0.002). The level of urinary miR-146a reversely correlated with the urinary expression of TNF-α (r = -0.247, P = 0.012). Our results suggested that miR-146a and miR-155 might play important roles in the pathophysiology of SLE and the levels of urinary miR-146a and miR-155 could be used as potential markers for diagnosis, disease activity, and therapeutic response.

Relationship of intrarenal gene expression and the histological class of lupus nephritis -- a study on repeat renal biopsy.

OBJECTIVE: To study the role of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)/Fn14 and the interferon-inducible protein (IP-10)/CXCR3 axis in lupus nephritis (LN). METHODS: We studied 113 patients with LN who had had repeat renal biopsies. Glomerular and tubulointerstitial messenger RNA expression of TWEAK, Fn14, IP-10, and CXCR3 were quantified. RESULTS: Glomerular Fn14 expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p = 0.016), and increased when changed from membranous to proliferative or mixed nephritis (p = 0.0006). On the other hand, tubulointerstitial TWEAK expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p = 0.004), and increased when changed from membranous nephropathy to proliferative nephritis (p = 0.010). Tubulointerstitial IP-10 expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p < 0.0001). Histological activity index correlated significantly with the glomerular expression of Fn14 (r = 0.421, p < 0.0001) and tubulointerstitial expression of TWEAK (r = 0.413, p < 0.0001) and IP-10 (r = 0.472, p < 0.0001). CONCLUSION: Glomerular Fn14 and tubulointerstitial TWEAK and IP-10 expression appeared to have consistent changes in relation to the histological class of LN and correlated with the histological activity index. Our findings suggest a specific role of these genes in the pathogenesis of LN.

Monitoring of urinary messenger RNA levels for the prediction of flare in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by disease flares and remission. We hypothesize that in clinically quiescent SLE patients, the mRNA level of target genes in the urinary sediment is an early indicator of disease flare. METHODS: From a cohort of 134 adult SLE patients prospectively followed for 56 weeks, we identified 19 patients with a single disease flare. The mRNA level of eight pre-defined target genes in their urinary sediment before disease flare was compared to 19 matched controls with no disease flare during the same period. RESULTS: Urinary mRNA level remained static in the control group during the study period. Before disease flare, there was a significant increase in the mRNA level of monocyte chemotactic protein (MCP)-1 and forkhead box P3 (FOXP3), and decrease in interleukin (IL)-17 and GATA-3, in the urinary sediment. The mRNA level of FOXP3 in urinary sediment increases 8 weeks prior to a flare, which precedes the corresponding change in serum complement and anti-DNA antibody titer, while that of MCP-1, IL-17, and GATA3 began to change 4 weeks prior to a flare. The same pattern of change in urinary mRNA level was observed in patients with mild-to-moderate or severe flare, and those with renal or non-renal flare. The SLE Disease Activity Index (SLEDAI) score at the time of flare significantly correlated with the change in urinary level of IL-17 (r=-0.462, p=0.046) and GATA-3 (r=-0.455, p=0.05), but not MCP-1 or FOXP3, prior to the flare. CONCLUSION: Monitoring of MCP-1, IL-17, GATA-3 and FOXP3 mRNA level in urinary sediment may provide an early clue for detecting disease flare in SLE patients.

High prevalence of subclinical left ventricular dysfunction in patients with psoriatic arthritis.

OBJECTIVE: Endothelial dysfunction and early atherosclerosis have been found in patients with psoriatic arthritis (PsA) without cardiovascular disease (CVD) risk factors. Few studies have investigated whether there is any early impairment of myocardial function. The aims of our study were to determine the prevalence of subclinical left ventricular (LV) dysfunction in PsA patients and the disease-related risk factors. METHODS: Ninety-four PsA patients without clinical evidence of CVD and 63 healthy subjects were enrolled. All underwent conventional echocardiography and tissue Doppler imaging. RESULTS: Sixty-one (65%) patients with PsA had evidence of subclinical LV dysfunction as defined by mean myocardial peak systolic velocity (Sm) of basal 6 segments < 4.4 cm/s, lateral E' < 11.5 cm/s, and/or lateral E/E' > 10. Thirty-six (38%) patients had only diastolic dysfunction, 4 (4%) had only systolic dysfunction, and 21 (22%) had both systolic and diastolic dysfunction. PsA patients with subclinical LV dysfunction were older, had a higher age at diagnosis of PsA and of psoriasis, a longer disease duration, a higher prevalence of hypertension and hyperlipidemia, higher levels of serum creatinine, and more antihypertensive treatment than those with normal LV function. Multivariate regression showed that age at diagnosis of PsA > 40 years (OR 3.388, 95% CI 1.065-10.777, p = 0.039) and hypertension (OR 4.732, 95% CI 1.345-16.639, p = 0.015) were independent predictors of subclinical LV dysfunction. CONCLUSION: PsA patients without established CVD disease and in the absence of traditional CV risk factors have a high prevalence of subclinical LV dysfunction.

Anti-inflammatory activities of Chinese herbal medicine sinomenine and Liang Miao San on tumor necrosis factor-α-activated human fibroblast-like synoviocytes in rheumatoid arthritis.

AIM OF THE STUDY: Sinomenine, an alkaloid isolated from the root of Sinomenium acutum, has been used to alleviate the symptoms of rheumatic diseases. Liang Miao San (LMS), composed of the herbs Rhizoma Atractylodis (Cangzhu) and Cotex Phellodendri (Huangbai), is another traditional Chinese medicine formula for rheumatoid arthritis (RA) treatment. Although numerous studies have demonstrated the potential anti-inflammatory activities of sinomenine and LMS, the underlying intracellular mechanisms regulating the anti-inflammatory activities of sinomenine and LMS on human primary fibroblast-like synoviocytes (FLS) from RA patients and normal control subjects have not been elucidated. MATERIALS AND METHODS: We investigated the in vitro anti-inflammatory activity of sinomenine and LMS on inflammatory cytokine tumor necrosis factor (TNF)-α-mediated activation of human normal and RA-FLS. The underlying intracellular signaling molecules were analyzed quantitatively using flow cytometry. RESULTS: Sinomenine was found to significantly inhibit TNF-α induced cell surface expression of vascular cell adhesion molecule (VCAM)-1 and release of inflammatory cytokine and chemokine IL-6, CCL2 and CXCL8 from both normal and RA-FLS (all p<0.05). Moreover, the suppression of sinomenine on TNF-α induced VCAM-1 expression and IL-6 release of RA-FLS was significantly higher than that of normal FLS (p<0.05). LMS significantly inhibited TNF-α-induced inflammatory chemokines CXCL10 and CCL5 release from both normal and RA-FLS, with significantly higher suppression on CXCL10 secretion in RA-FLS than that of normal FLS (all p<0.05). Further investigations showed that sinomenine and LMS could significantly suppress TNF-α-induced phosphorylation of inhibitor κBα and extracellular signal-regulated protein kinase, the central signaling molecules mediating TNF-α-induced VCAM-1 expression and chemokine production. CONCLUSION: Our results therefore provide a new insight into the differential anti-inflammatory activities of sinomenine and LMS through the suppression of TNF-α-activated FLS by modulating distinct intracellular signaling pathways in RA.

Serum and urinary cell-free MiR-146a and MiR-155 in patients with systemic lupus erythematosus.

OBJECTIVE: Recent studies showed that micro-RNA play important roles in the pathogenesis of autoimmune diseases. We studied the levels of miR-146a and miR-155 in the serum and urinary supernatant of patients with systemic lupus erythematosus (SLE). METHODS: The serum and urinary supernatant levels of miR-146a and miR-155 were determined by real-time quantitative polymerase chain reaction in 40 patients with SLE and 30 healthy controls. RESULTS: Compared to controls, serum miR-146a and miR-155 levels were lower, and the urinary level of miR-146a was higher, in SLE. Estimated glomerular filtration rate (eGFR) correlated with both serum miR-146a (r = 0.519, p = 0.001) and miR-155 (r = 0.384, p = 0.014). Serum miR-146a inversely correlated with proteinuria (r = -0.341, p = 0.031) and the SLE Disease Activity Index (r = -0.465, p = 0.003). Serum miR-146a and miR-155 levels also correlated with red blood cell count, platelet count, and lymphocyte count. After treatment with calcitriol for 6 months, serum miR-146a level of SLE patients increased significantly (p < 0.001), and its change inversely correlated with the level of calcium-phosphate product (r = -0.466, p = 0.003). CONCLUSION: The results suggested that serum miR-146a and miR-155 participate in the pathophysiology of SLE and might be used as biomarkers of SLE.

Comparison of 4 functional indexes in psoriatic arthritis with axial or peripheral disease subgroups using Rasch analyses.

OBJECTIVE: Rasch item response theory analysis is essential in evaluating measurement tools in specific disease cohorts. We compared the performance of 4 functional indexes in patients with psoriatic arthritis (PsA) in axial or peripheral disease subgroups. METHODS: A cross-sectional study was performed in a single center. Functional outcomes assessed by the Health Assessment Questionnaire (HAQ), Bath Ankylosing Spondylitis Functional Index (BASFI), Dougados Functional Index (FI), and the physical functioning scale of the Medical Outcome Study Short-form 36 (SF-36-PF) were analyzed by the Rasch model for item fit, item separation, measurement span, and distribution properties. Patient subgroups with axial or peripheral disease were analyzed for differential item functioning (DIF). RESULTS: One hundred eight patients with PsA were assessed. The 4 functional indexes were highly correlated with each other and moderately correlated with patients' perception of health and pain scores. Floor effects were less marked in SF-36-PF. The 4 indexes satisfied the unidimensionality assumption of the Rasch model. HAQ and SF-36-PF had better information-weighted fit statistics (INFIT) and outlier-sensitive (OUTFIT) statistics. HAQ had the poorest item separation. SF-36-PF had the highest item separation (6.99), reliability (0.85), and the longest span of item threshold (9.03 logits). Only 1 and 2 items in BASFI and Dougados-FI had DIF in patients with sacroiliitis. CONCLUSION: HAQ, BASFI, Dougados-FI, and SF-36-PF provide unidimensional measures of functional disability in PsA. SF-36-PF was the best in terms of less floor effect, highest item separation, longest span of item threshold, and better distributional properties. BASFI and Dougados-FI behaved similarly in patients with and without sacroiliitis and conferred no superiority in patients with axial disease.

Climatic influence on the prevalence of noncutaneous disease flare in systemic lupus erythematosus in Hong Kong.

OBJECTIVE: It is generally agreed that there is a seasonal variation in the prevalence of cutaneous manifestations of systemic lupus erythematosus (SLE). We investigated whether there is seasonal variation in the incidence of noncutaneous lupus flare in Hong Kong. METHODS: We reviewed all noncutaneous lupus flare in 222 consecutive patients with SLE followed in our clinic from 1995 to 2005. Specific organ involvement of each flare was reviewed. The variation in the prevalence of lupus flare by calendar month and the relation with climatic factors were determined. RESULTS: The total followup was 18,412 patient-months. In total, there were 313 episodes of noncutaneous flare recorded in 129 patients. There were more lupus flares in December and January [2.31 episodes, vs 1.58 episodes per 100 patient-months for other calendar months; relative risk (RR) 1.46, 95% CI 1.12-1.90, p = 0.004], and more flares of lupus nephritis in December and January (1.14 episodes, vs 0.60 episodes per 100 patient-months for other calendar months; RR 1.90, 95% CI 1.29-2.80, p = 0.001). There were more cases of membranous nephropathy in December and January (0.46 episode, vs 0.18 episode per 100 patient-months for other calendar months; RR 2.59, 95% CI 1.36-4.93, p = 0.0027), while the variation in prevalence of proliferative lupus nephritis was not statistically significant. There was also a significant U-shape correlation between the rate of lupus flare and the monthly average environmental temperature (r = 0.802, p = 0.0096), with higher flare rate at extremes of temperature. CONCLUSION: We found substantial seasonal variation in the incidence of noncutaneous flare in our SLE patients, with peak incidence in December and January. There was a U-shaped relation between environmental temperature and the prevalence of noncutaneous flare. Keeping a warm living environment and avoiding exposure to extremes of temperature may help to reduce flare for SLE patients in subtropical countries.

Elevated gene expression of Th1/Th2 associated transcription factors is correlated with disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: T-box expressed in T cells (T-bet) and GATA-binding protein 3 (GATA-3) are transcriptional factors that play a crucial role in Th1 and Th2 development. We investigated the immunomodulatory roles of T-bet and GATA-3 and Th1/Th2 related cytokines in the pathogenesis of systemic lupus erythematosus (SLE) and their association with disease activity. METHODS: Gene expressions of T-bet, GATA-3, interferon-gamma (IFN-gamma), and interleukin 4 (IL-4) in peripheral blood mononuclear cells, and plasma concentrations of the Th1/Th2 cytokines IFN-gamma, IL-18, and IL-4, were assayed in 80 patients with SLE and 40 sex and age matched healthy subjects by real-time quantitative polymerase chain reaction and ELISA. RESULTS: The mRNA levels of T-bet and IFN-gamma and the relative expression levels of T-bet/GATA-3 and IFN-gamma/IL-4 were significantly higher, in contrast to the lower expressions of GATA-3 and IL-4, in SLE patients than controls (all p < 0.05). In all SLE patients, there were significant correlations in mRNA expression of T-bet with IFN-gamma (r = 0.590, p < 0.0001), and of GATA-3 with IL-4 (r = 0.245, p = 0.029). The relative expressions of T-bet/GATA-3 and IFN-gamma/IL-4 correlated with lupus disease activity (r = 0.229, p = 0.042; r = 0.231, p = 0.040, respectively). Plasma IL-18 concentration was increased significantly in all SLE patients (p < 0.05). The elevated plasma Th1/Th2 cytokine ratio IL-18/IL-4 correlated positively with disease activity in all SLE patients (r = 0.250, p = 0.025). CONCLUSION: There is an association between expression of Th1/Th2 transcription factors and cytokines in SLE. The elevated gene expressions of Th1/Th2 transcription factors and cytokines should provide a useful tool for assessing the functional status of T-helper lymphocytes in SLE disease development.