Esther Guadalupe Corona-Sanchez

Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P < 0.001). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P < 0.01), and lower levels of high density lipoprotein cholesterol (HDL-c) (P = 0.02). The cIMT correlated with levels of anti-CCP (r = 0.513, P = 0.001), CRP (r = 0.799, P < 0.001), TNFα (r = 0.642, P = 0.001), and IL-6 (r = 0.751, P < 0.001). In multiple regression analysis, cIMT was associated with CRP (P < 0.001) and anti-CCP levels (P = 0.03). Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events.

Anti-Cyclic Citrullinated Peptide Antibodies and Severity of Interstitial Lung Disease in Women with Rheumatoid Arthritis

Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2) are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD). Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT) were compared with 42 RA without lung involvement (RA only). Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2u2009U/mL, P < 0.001). In the logistic regression analysis after adjustment for age, disease duration (DD), smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX) treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P = 0.003) and + RF (P = 0.002). In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P = 0.02) and with fibrosis score DD (P = 0.01), anti-CCP2 titers (P < 0.001), and MTX treatment duration (P < 0.001). Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD.

Comparison of Two Assays to Determine Anti-Citrullinated Peptide Antibodies in Rheumatoid Arthritis in relation to Other Chronic Inflammatory Rheumatic Diseases: Assaying Anti-Modified Citrullinated Vimentin Antibodies Adds Value to Second-Generation Anti-Citrullinated Cyclic Peptides Testing

Determination of anti-citrullinated peptide antibodies (ACPA) plays a relevant role in the diagnosis of rheumatoid arthritis (RA). To date, it is still unclear if the use of several tests for these autoantibodies in the same patient offers additional value as compared to performing only one test. Therefore, we evaluated the performance of using two assays for ACPA: second-generation anti-citrullinated cyclic peptides antibodies (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies for the diagnosis of RA. We compared three groups: RA (n = 142), chronic inflammatory disease (CIRD, n = 86), and clinically healthy subjects (CHS, n = 56) to evaluate sensitivity, specificity, predictive values, and likelihood ratios (LR) of these two assays for the presence of RA. A lower frequency of positivity for anti-CCP2 was found in RA (66.2%) as compared with anti-MCV (81.0%). When comparing RA versus other CIRD, sensitivity increased when both assays were performed. This strategy of testing both assays had high specificity and LR+. We conclude that adding the assay of anti-MCV antibodies to the determination of anti-CCP2 increases the sensitivity for detecting seropositive RA. Therefore, we propose the use of both assays in the initial screening of RA in longitudinal studies, including early onset of undifferentiated arthritis.

-383 A/C tumor necrosis factor receptor 1 polymorphism and ankylosing spondylitis in Mexicans: a preliminary study.

The objective of this study was to evaluate the differences in allele and genotype frequencies of −383 tumor necrosis factor receptor 1 (TNFR1) polymorphism between ankylosing spondylitis (AS) and controls. Mexican Mestizos with AS were matched by gender, age, and ethnicity with healthy controls and compared in allele and genotype frequencies of the −383 TNFR1 polymorphism. Polymorphisms were genotyped using PCR–RFLP. The AA genotype occurred at a higher frequency in the AS group (92%) compared with controls (79%, Pxa0=xa00.03). A allele was increased in AS (96% vs. 88%, Pxa0=xa00.015) and was associated with genetic susceptibility for AS (odds ratioxa0=xa03.48, 95% CIxa0=xa01.23–10.61). This preliminary study is the first assessing the association of the −383 A/C TNFR1 polymorphism with AS, although it has the limitation of a small sample size. These data are of interest for the genetic epidemiology of AS in the Mexican population, requiring further investigation in other countries.

Circulating E-selectin and tumor necrosis factor-α in extraarticular involvement and joint disease activity in rheumatoid arthritis

In this cross-sectional study, we assessed the relationship between circulating TNF-α and E-selectin (sE-selectin) with extraarticular involvement and severity of joint disease in RA. We compared 56 patients who had RA and extraarticular involvement (ExRA) with a group of 84 patients with only articular involvement (non-ExRA). ExRA had higher circulating TNF-α than non-ExRA (32xa0±xa09 vs. 28xa0±xa06xa0pg/mL, Pxa0=xa00.002). sE-selectin levels did not differ between both groups. sE-selectin correlated with tender joint count (rhoxa0=xa00.19, Pxa0=xa00.03), morning stiffness (rhoxa0=xa00.19, Pxa0=xa00.03), severity of pain (rhoxa0=xa00.21, Pxa0=xa00.02), disease activity (assessed by the patient) (rhoxa0=xa00.21, Pxa0=xa00.02), HAQ-DI (rhoxa0=xa00.29, Pxa0=xa00.004), and rheumatoid factor titers (rhoxa0=xa00.31, Pxa0=xa0<0.001). Circulating TNF-α had no correlation with sE-selectin or disease activity. We concluded that sE-selectin correlated with severity of joint disease, further follow-up studies should evaluate if sE-selectin is useful as prognosis marker for progression of articular damage.

Circulating leptin and bone mineral density in rheumatoid arthritis.

Objective. To evaluate the association between circulating leptin and bone mineral density (BMD) in patients with rheumatoid arthritis (RA). Methods. One-hundred thirty postmenopausal women with RA were assessed for body mass index (BMI), disease characteristics, history of drug use, rheumatoid factor, and erythrocyte sedimentation rate (ESR). BMD (g/cm2) was determined in the hip and spine by DEXA. Serum leptin concentrations were measured by ELISA. Spearman’s correlation coefficients (rho) were determined between BMD and leptin and other variables. A multiple regression analysis was used to adjust for confounders. Results. Patients’ serum leptin levels varied widely (range 2–128 ng/ml). Thirty-three patients (25%) had osteoporosis. Higher levels of leptin correlated significantly with BMD in the lumbar spine (rho = 0.17, p = 0.04) and total hip (rho = 0.21, p = 0.01). The variables that were negatively correlated with BMD were age, duration of menopause, and ESR. After adjustment for confounders, leptin was no longer associated with BMD. In the multivariate model, factors that remained associated with BMD in the total hip were age (p = 0.021) and BMI (p = 0.003); and the factors that remained associated with BMD in the lumbar spine were BMI (p = 0.03) and ESR (p = 0.01). Conclusion. No relevant association was found between circulating leptin levels and BMD in patients with RA in this cross-sectional study. Followup studies are needed to evaluate whether abnormal leptin levels confer a risk for fractures due to osteoporosis.

Modifications in Lipid Levels Are Independent of Serum TNF-α in Rheumatoid Arthritis: Results of an Observational 24-Week Cohort Study Comparing Patients Receiving Etanercept Plus Methotrexate or Methotrexate as Monotherapy

Objective. To compare the modifications in lipids between patients with rheumatoid arthritis (RA) receiving etanercept plus methotrexate (ETA + MTX) versus methotrexate (MTX) and their relationship with serum levels of tumor necrosis factor-alpha (TNF-α). Methods. In an observational cohort study, we compared changes in lipid levels in patients receiving ETA + MTX versus MTX in RA. These groups were assessed at baseline and at 4 and 24 weeks, measuring clinical outcomes, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and TNF-α. Results. Baseline values for lipid levels were similar in both groups. HDL-C levels increased significantly only in the ETA + MTX group (from 45.5 to 50.0u2009mg/dL at 4 weeks, a 10.2% increase, P < 0.001, and to 56.0u2009mg/dL at 24 weeks, a 25.1% increase, P < 0.001), while other lipids underwent no significant changes. ETA + MTX also exhibited a significant increase in TNF-α (44.8u2009pg/mL at baseline versus 281.4u2009pg/mL at 24 weeks, P < 0.001). The MTX group had no significant changes in lipids or TNF-α. Significant differences in HDL-C between groups were observed at 24 weeks (P = 0.04) and also in TNF-αu2009u2009(P = 0.01). Conclusion. HDL-C levels increased significantly following treatment with ETA + MTX, without a relationship with decrease of TNF-α.

Polymorphism rs2073618 of the TNFRSF11B (OPG) Gene and Bone Mineral Density in Mexican Women with Rheumatoid Arthritis

Osteoporosis (OP) is highly prevalent in rheumatoid arthritis (RA) and is influenced by genetic factors. Single-nucleotide polymorphism (SNP) rs2073618 in the TNFRSF11B osteoprotegerin (OPG) gene has been related to postmenopausal OP although, to date, no information has been described concerning whether this polymorphism is implied in abnormalities of bone mineral density (BMD) in RA. We evaluated, in a case-control study performed in Mexican-Mestizo women with RA, whether SNP rs2073618 in the TNFRSF11B gene is associated with a decrease in BMD. RA patients were classified as follows: (1) low BMD and (2) normal BMD. All patients were genotyped for the rs2073618 polymorphism by PCR-RFLP. The frequency of low BMD was 74.4%. Higher age was observed in RA with low BMD versus normal BMD (62 and 54 years, resp.; p < 0.001). Worse functioning and lower BMI were observed in RA with low BMD (p = 0.003 and p = 0.002, resp.). We found similar genotype frequencies in RA with low BMD versus RA with normal BMD (GG genotype 71% versus 64.4%, GC 26% versus 33%, and CC 3% versus 2.2%, resp.; p = 0.6). We concluded that in Mexican-Mestizo female patients with RA, the rs2073618 polymorphism of the TNRFS11B gene is not associated with low BMD.