Monocyte-to-high-density lipoprotein ratio as a predictor for patients with Takayasu arteritis and coronary involvement: a double-center, observational study.

Background: The implication of the monocyte-to-high-density lipoprotein ratio (MHR) in Takayasu arteritis (TAK) remains unclear. Objective: We aimed to assess the predictive value of the MHR to identify coronary involvement with TAK and determine the patient prognosis. Methods: In this retrospective study, 1,184 consecutive patients with TAK were collected and assessed, and those who were initially treated and with coronary angiography were enrolled and classified according to coronary involvement or no involvement. Binary logistic analysis was performed to assess coronary involvement risk factors. Receiver-operating characteristic analysis was used to determine the MHR value to predict coronary involvement in TAK. Major adverse cardiovascular events (MACEs) were recorded in patients with TAK and coronary involvement within a 1-year follow-up, and Kaplan-Meier survival curve analysis was conducted to compare MACEs between them stratified by the MHR. Results: A total of 115 patients with TAK were included in this study, and 41 of them had coronary involvement. A higher MHR was found for TAK with coronary involvement than for TAK without coronary involvement (P = 0.014). Multivariate analysis showed that the MHR is an independent risk factor for coronary involvement in TAK (odds ratio: 92.718, 95% confidence interval (CI): 2.813-3056.291, P = 0.011). With the best cut-off value of 0.35, the MHR identified coronary involvement with 53.7% sensitivity and 68.9% specificity [area under the curve (AUC): 0.639, 95% CI: 0.544-0.726, P=0.010] and identified left main disease and/or three-vessel disease (LMD/3VD) with 70.6% sensitivity and 66.3% specificity (AUC: 0.704, 95% CI: 0.612-0.786, P = 0.003) in TAK. Combined with other variables, the MHR identified coronary involvement with 63.4% sensitivity and 90.5% specificity (AUC: 0.852, 95% CI: 0.773-0.911, P < 0.001), and identified LMD/3VD with 82.4% sensitivity and 78.6% specificity (AUC: 0.827, 95% CI: 0.720-0.934, P < 0.001) in TAK. A total of 39 patients with TAK and coronary involvement were followed up for 1 year, and 5 patients suffered a MACE. Those with an MHR >0.35 had a higher MACE incidence than their counterparts with an MHR ≤0.35 (χ2 = 4.757, P = 0.029). Conclusions: The MHR could be a simple, practical biomarker for identifying coronary involvement and LMD/3VD in TAK and predicting a long-term prognosis.

Clinical study of carotid superb microvascular imaging in evaluating the activity of Takayasu's arteritis.

Objective: The goal of this study is to use superb microvascular imaging (SMI) to observe neovascularization in the carotid vessel wall to identify potential Takayasu's arteritis (TAK) inflammation markers. Methods: Bilateral carotid arteries from 96 patients with TAK were imaged by a Doppler ultrasound and SMI. The one-way analysis of variance (ANOVA) was used to document significant differences between the activity and inactivity stages of TAK and the factors closely related to its activity in the binary logistics regression equation. Clinical and laboratory data included age, gender, duration of disease, treatment history, NIH score, erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein. Imaging data included the arterial wall thickness, degree of lesion, SMI grade, and arterial aneurysm formation. Results: There were 45 patients in the active TAK stage and 51 in the inactive stage. The one-way ANOVA showed significant differences in SMI (p = 0.001) and ESR (p = 0.022) between the active and inactive groups. The binary logistics regression analysis showed that SMI was an independent risk factor for TAK activity (B = -1.505, S.E = 0.340, Wald = 19.528, OR = 0.222 95%, CI = 0.114-0.433, p < 0.01). Using SMI G1 or G2 as the cutoff values for the diagnosis of active TAK, the positive predictive value, sensitivity, and specificity were 60 and 86%, 84% and 56%, and 54% and 92%, respectively. Conclusion: The SMI grade is a potential marker of disease activity in patients with TAK.

Characteristics of B cells and immunoglobulin profile in Takayasu's arteritis.

OBJECTIVES: Disorders of humoral immunity in Takayasu's arteritis (TAK) have not been well explored. This study describes the characteristics of B cells and immunoglobulin (Ig) profile in patients with TAK. METHODS: Peripheral B cell populations assessed using flow cytometry and serum Ig levels assessed using a biochemical analyser in 98 newly diagnosed patients with TAK were analysed and compared with those of 31 patients with systemic lupus erythematosus (SLE) and 60 healthy controls (HCs). CD19+ B cell and IgG infiltration to the aortic tissue was evaluated by immunohistochemical staining. RESULTS: The proportion of peripheral CD3-CD19+ B cells and levels of serum IgG in TAK were lower than those in SLE, but higher than those in HCs. CD3-CD19+ B cell counts were higher in TAK than in HCs. Serum IgG and IgG1 levels were higher in active TAK than in non-active TAK. In TAK, positive correlations of serum IgG levels with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Kerr score, and Indian Takayasu Clinical Activity Score (ITAS2010, ITAS-A) were observed before immunotherapy. After 6 months of immunotherapy, serum Ig levels significantly decreased. Positive correlations between the changes in IgG levels and values of ESR, CRP, Kerr score, and ITAS-A were detected. Immunohistochemical staining confirmed CD19+ B cell and IgG infiltration to the aortic wall in patients with TAK. CONCLUSIONS: Enhanced B cells might contribute to the pathogenesis of TAK, and serum IgG levels could serve as a simple, useful biomarker to assess disease activity and monitor treatment response in TAK.

Characteristics and risk factors of severe coronary artery disease in systemic lupus erythematosus: A multicenter, Chinese Rheumatism Date Center database study.

AIM: Systemic lupus erythematosus (SLE) with severe coronary artery disease (CAD) is associated with increased mortality. This study aimed to assess the characteristics and risk factors of severe CAD in SLE. METHOD: This multicenter, cross-sectional study enrolled consecutive patients with SLE included in the Chinese Rheumatism Date Center registry. Patients with severe CAD including angiography-confirmed stenosis ≥50% in the left main, ≥70% in other major coronary arteries, or myocardial infarction were classified into the CAD group. Patients without CAD were classified into the control group. Subgroups were stratified according to age (set as above and below 45 and 50 for men and women, respectively) and gender. Binary logistic regression analysis was performed to determine independent risk factors of severe CAD in SLE. RESULTS: Forty-three patients had severe CAD from a total of 3744 patients with SLE, 30 of whom were female; 35 belonged to the older age group and 8 belonged to the younger age group. In older patients, independent risk factors included age, 5 major CAD risk factors, SLE Disease Activity Index 2000 (SLEDAI-2K), hyperuricemia, and corticosteroid exposure. In younger patients, the risk factors were 5 major CAD risk factors and positive antiphospholipid antibody (APL). Male risk factors were age and 5 major CAD risk factors, whereas female risk factors were age, 5 major CAD risk factors, SLEDAI-2K, and positive APL. Three-vessel disease was most prevalent in patients with severe CAD. CONCLUSION: We recommend screening for severe CAD in patients with SLE with age- and gender-stratified risk factors.

Male Patients with Takayasu Arteritis and Coronary Artery Involvement are Prone to Have Serious Coronary Stenosis and High Mortality.

BACKGROUND: Takayasu arteritis (TAK) is a rare autoimmune vasculitis that predominantly affects the aorta and its major branches, including the coronary arteries. Information is limited regarding sex-specific differences in coronary artery involvement among TAK patients. OBJECTIVE: To assess the differences in coronary angiographic findings and long-term outcomes between male and female TAK patients with coronary artery involvement. METHODS: This retrospective cohort study included 87 TAK patients, grouped by sex, who underwent coronary angiography. General characteristics, clinical features, coronary angiographic findings, and therapeutic strategies were obtained from medical records. Major Adverse Cardiac Events (MACE), including death from any cause, myocardial infarction, repeated coronary artery revascularization, and rehospitalization due to unstable or progressive angina or heart failure occurring during follow-up, were also recorded. RESULTS: A total of 207 coronary lesions with stenosis were found in 87 TAK patients. The prevalence of ostial coronary lesions was lower in men than in women (9.1 vs. 23.9%, p=0.031). We observed less moderate stenosis (6.8 vs. 22.7%, p=0.018) and more severe stenosis or occlusion (70.5 vs. 46.0%, p=0.004) in the coronary lesions of male TAK patients. During the up to 7-year follow- up, death from any cause was greater in men than in women (21.4 vs. 1.5%, p=0.003); no other significant differences in MACE occurrence were observed between sexes. CONCLUSION: Among TAK patients with coronary artery involvement, males tend to have more serious coronary stenosis and a higher risk for long-term mortality than females.

Comparison of Clinical Features at the Onset of Takayasu's Arteritis According to Age and Sex.

BACKGROUND: Takayasu's arteritis (TA) is a large-vessel vasculitis that predominantly affects the aorta, pulmonary artery, and its main branches. The cause of TA is still unclear. OBJECTIVE: To identify the clinical characteristics of TA at onset in different patient groups. METHODS: The clinical manifestations, laboratory, and angiographic findings of 53 patients with TA based on age at onset and sex were retrospectively analysed. RESULTS: The ratio of the incidence of TA in males and females was 1:4. Chest pain, reduced glomerular filtration rate (GFR), and multivessel involvement were the most common symptoms at TA onset in male patients. 17% of patients had an onset age >40 years, and the percentage of TA patients >40 years old with chest pain was significantly higher [6 (66.7%) vs 13 (29.5%) and p=0.031] than that in TA patients <40 years old. However, their renal artery involvement [1 (11.1%) vs 21 (47.7%)), p=0.042], abdominal aorta lesion [0 (0.0%) vs 16 (38.1%), p=0.030], and multiple vessel involvement [2 (22.2%) vs. 32 (72.7%), p=0.004] were significantly less evident. Multivariate analysis showed that hypertension and thoracic aortic lesion were predisposing factors for TA diagnosis [odds ratio (OR)=3.918, 95% confidence interval (CI)=1.616-1566.185, p=0.026]. For patients with aortic insufficiency (OR=3.674, 95% CI=2.734-567.621, p=0.007) or aneurysm formation (OR=7.255, 95% CI=1.23-1628.614, p=0.044), ascending aortic lesion was an independent risk factor. Furthermore, patients >40 years with chest pain but no brachial pulse should be suspected to have TA. CONCLUSION: Hypertension and thoracic aortic lesion are predisposing factors for the diagnosis of TA. Male with TA was more prone to present with chest pain, multivessel involvement, and reduced GFR.

T-614 inhibits human aortic adventitial fibroblast proliferation and promotes interleukin-8 production in vitro.

OBJECTIVES: The effect and underlying mechanism of T-614 (iguratimod) on Takayasu's arteritis (TA) are unknown. Here, we report the effects of T-614 on cell proliferation and interleukin-8 (IL-8) production in human aortic adventitial fibroblasts (HAAFs) in vitro and explore its initial benefit in terms of vascular wall inflammation and remodeling for patients with TA. METHODS: HAAFs were cultured with 0, 5, 50, 100, or 250 µg/ml T-614 in the absence or presence of tumor necrosis factor-α (TNF-α) in vitro. Cell viability was determined by a modified MTT assay. Supernatant IL-8 levels were measured by enzyme-linked immunosorbent assays. RESULTS: In the presence of TNF-α, compared to that in the control group, cell viability of HAAFs significantly decreased in the 50, 100, and 250 µg/ml T-614 treatment groups (OD value: P < 0.01, P < 0.001, P < 0.001, respectively; survival fraction (SF): P < 0.05, P < 0.001, P < 0.001, respectively). However, there was no significant difference in cell viability between TNF-α-stimulated and unstimulated groups at the same concentration of T-614. In the absence or presence of TNF-α, T-614 suppressed HAAF cell viability dose-dependently (OD value: r = -0.915, P = 0.000; r = -0.926, P = 0.000, respectively; SF: r = -0.897, P = 0.000; r = -0.885, P = 0.000, respectively). Compared to that in the control group, in the absence of TNF-α, IL-8 levels in the 5 and 100 µg/ml T-614-treated groups were significantly higher (P < 0.05); in the presence of TNF-α, IL-8 levels in the 5, 50, and 100 µg/ml T-614-treated groups were significantly higher (P < 0.001, P < 0.001, P < 0.01, respectively). Further, there was a negative correlation between supernatant IL-8 levels and T-614 concentration in groups stimulated with TNF-α (r = -0.670, P = 0.000), but there was no significant correlation between these parameters in groups that were not stimulated with TNF-α. CONCLUSIONS: In the absence or presence of TNF-α, T-614 can inhibit HAAF proliferation and promote IL-8 production in vitro; therefore, it could be used to prevent adventitial thickening of the aorta and improve vascular remodeling in inflammatory environments in vitro and might provide a new immunotherapeutic intervention for TA.

IL-9-producing Th9 cells may participate in pathogenesis of Takayasu's arteritis.

Takayasu's arteritis (TAK) is a type of large vessel vasculitis which involves the aorta and its major branches. Interleukin (IL)-9 or IL-9-producing Th9 cells were found to be involved in pathogenesis of autoimmune arteritis such as giant cell arteritis, but IL-9 or Th9 cells in TAK were not well known. Here, this study aims to analyze the levels of serum IL-9 and their major source Th9 cells in TAK. With the help of cytometric bead array (CBA), a total of 21 patients with TAK were examined for serum levels of cytokines IL-4, IL-6, IL-8, IL-17, IL-10, TNF-α, IFN-γ, and IL-9. Flow cytometry techniques were used to examine the frequencies of Th9 cells from peripheral blood mononuclear cells (PBMCs) for 11 patients with active TAK and 10 healthy controls. Higher serum levels of serum IL-6 (P < 0.05), TNF-α (P < 0.05), and IL-9 level (P < 0.05) were observed in TAK patients compared to those of healthy controls. Higher frequencies of CD4+ IL-9+ T cells and CD4+ PU.1+ T cells in PBMCs and IL-9+ PU.1+ T cells in CD4+ T cells were observed in active TAK patients than those in healthy controls (all P < 0.01). The levels of IL-9 had a positive correlation with ESR (r = 0.975, P = 0.015) in these cases. Our data suggested that Th9 cells and IL-9 could possibly be involved in the pathogenesis of TAK.

[Clinical significance of serum 25-hydroxyvitamin D in female patients with rheumatoid arthritis].

OBJECTIVE: The research aimed to evaluate the level and clinical significance of serum 25-hydroxyvitamin D in female patients with rheumatoid arthritis (RA). METHODS: Totally 82 untreated RA female patients (RA group) and 32 healthy females (control group) were enrolled.According to the disease activity score in 28 joints (DAS28), patients in RA group were divided into remission stage group (<2.6 scores, 32 cases) and active stage group (≥2.6 scores, 50 cases). The correlations of 25-hydroxyvitamin D (25-(OH)-D) level with related indicators were analyzed. RESULTS: (1)The levels of serum 25-(OH)-D in female RA active stage group were significantly lower than those in control group [(12.5±6.3) µg/L vs (26.6±5.3) µg/L ] (P<0.01). The levels of serum 25-(OH)-D in female RA remission stage group were significantly lower than those in control group [(14.2±7.2) µg/L vs (26.6±5.3) µg/L] (P<0.01). (2)Serum 25-(OH)-D levels were inversely associated with C reactive protein (CRP), erythrocyte sedimentation rate (ESR), DAS28 score (r=-0.575, r=-0.528, r=-0.354, P<0.05) in female RA active stage group, but not in female RA remission stage group (P>0.05). (3)In active stage group, the 25-(OH)-D levels of premenopausal RA patients were negatively correlated with CRP, ESR, DAS28 (r=-0.707, r=-0.625, r=-0.487, P<0.05), but not in postmenopausal RA patients (P>0.05). CONCLUSIONS: The 25-(OH)-D levels in serum are reduced in female patients with RA.Serum 25-(OH)-D level can be a marker to monitor the disease activity in RA premenopausal female patients.

[Study on polymorphic Hind III restriction site of the Y chromosome and essential hypertension in Tangshan district].

OBJECTIVE: Since males are at higher risk of cardiovascular diseases than females, the aim of the study was to examine whether there is an association between BP and a polymorphic Hind III biallelic marker in nonrecombining region of Y chromosome in essential hypertension in Tangshan district in China. METHODS: In the study, 225 patients with essential hypertension and 187 healthy people were enrolled into this study as control group. DNA was extracted from white blood cell. Segments of polymorphic Hind III restriction site of the Y chromosome were amplified from DNA by polymerase chain reaction (PCR). PCR products were restricted with 10 U of Hind III for a night at 37 degrees C. The digested products were subjected to electrophoresis in 3% agarose gels, and stained with ethidium bromide. RESULTS: We amplified 178 controls (95.2%) and 216 essential hypertensive patients (96.0%) successfully. Hind III(-) genotype was found in 45.8% of the men in essential hypertension and in 32.0% of the men in the controlled group. The Hind III(-) genotype was significantly higher than that in the controls (chi2 = 7.782, P = 0.007). However, the Hind III(+) genotype was lower in SBP (133.16 mm Hg +/- 21.60 mm Hg vs. 143.58 mm Hg +/- 24.16 mm Hg, P < 0.001), DBP (82.82 mm Hg +/- 11.72 mm Hg vs. 86.82 mm Hg +/- 12.65 mm Hg, P = 0.001), pulse pressure (50.34 mm Hg +/- 14.31 mm Hg vs. 56.76 mm Hg +/- 14.20 mm Hg, P < 0.001) and mean arterial pressure (99.59 mm Hg +/- 14.19 mm Hg vs. 105.74 mm Hg +/- 15.31 mm Hg, P < 0.001) than the Hind III(-) genotype. CONCLUSION: Polymorphic Hind III restriction site of the Y chromosome seemed to be associated with essential hypertension in Tangshan district in China.