YKL-40 serum levels are predicted by inflammatory state, age and diagnosis of idiopathic inflammatory myopathies.

YKL-40 increase according to the aging process, and its functions have been associated with tissue remodeling and systemic inflammation. In Rheumatoid Arthritis (RA) it has been proposed as a possible biomarker of activity and severity, however; in the field of idiopathic inflammatory myopathies (IIM) the role of YKL-40 in IIM is not clear. Thus, we aimed to evaluate if there is an association between the serum levels and muscle tissue expression of YKL-40 with age, IIM phenotype, muscle strength and myositis disease activity. The main finding was that age is the most important variable that affects the YKL-40 serum levels. In muscle biopsy, we observed that YKL-40 is mainly expressed in infiltrating lymphoid cells than in muscle tissue. Using ANCOVA according to the b-coefficients, YKL-40 serum levels are predicted by inflammatory state, age, and IIM diagnosis.

Anti-Drug Antibodies in the Biological Therapy of Autoimmune Rheumatic Diseases.

Autoimmune rheumatic diseases are a cluster of heterogeneous disorders that share some clinical symptoms such as pain, tissue damage, immune deregulation, and the presence of inflammatory mediators. Biologic disease-modifying antirheumatic drugs are some of the most effective treatments for rheumatic diseases. However, their molecular and pharmacological complexity makes them potentially immunogenic and capable of inducing the development of anti-drug antibodies. TNF inhibitors appear to be the main contributors to immunogenicity because they are widely used, especially in rheumatoid arthritis. Immunogenicity response on these treatments is crucial since the appearance of ADAs has consequences in terms of safety and efficacy. Therefore, this review proposes an overview of the immunogenicity of biological agents used in autoimmune rheumatic diseases highlighting the prevalence of anti-drug antibodies.

Comparison of Fear of COVID-19 in Medical and Nonmedical Personnel in a Public Hospital in Mexico: a Brief Report.

The world is social distancing, and compulsory confinement has caused stress, psychological instability, stigmatization, fear, and discrimination in the general population. In this cross-sectional survey study, we administered the Fear of COVID-19 Scale (FCV-19S) to hospital medical and nonmedical personnel. A total of 1216 participants were surveyed from May 25 to May 29 of 2020. We asked all the staff for their participation in the study, and physical copies of the survey were distributed to the staff willing to participate. All surveys were answered anonymously. We found that the global FCV-19S mean score was 16.4 ± 6.1, with a significant difference between women and men's scores. Medical students presented higher scores than experienced medical personnel. Additionally, the medical and nursing personnel presented a higher level of fear than hospital staff who did not work directly with COVID-19 patients. Our findings suggest that greater knowledge of medicine or infectious diseases could decrease the overall psychological impact of the pandemic disease.

Autoantibodies in the pathogenesis of idiopathic inflammatory myopathies: Does the endoplasmic reticulum stress response have a role?

Idiopathic inflammatory myopathies (IIMs) are a group of rare, acquired autoimmune diseases characterized by profound muscle weakness and immune cell invasion into non-necrotic muscle. They are related to the presence of antibodies known as myositis-specific antibodies and myositis-associated antibodies, which are associated with various IIM phenotypes and the clinical prognosis. The possibility of the participation of other pathological mechanisms involved in the inflammatory response in IIM has been proposed. Such mechanisms include the overexpression of major histocompatibility complex class I in myofibers, which correlates with the activation of stress responses of the endoplasmic reticulum (ER). Taking into account the importance of the ER for the maintenance of homeostasis of the musculoskeletal system in the regulation of proteins, there is probably a relationship between immunological and non-immunological processes and autoimmunity, and an example of this might be IIM. We propose that ER stress and its relief mechanisms could be related to inflammatory mechanisms triggering a humoral response in IIM, suggesting that ER stress might be related to the triggering of IIMs and their auto-antibodies' production.

Impaired muscle strength is associated with ultrastructure damage in myositis.

The muscle fiber ultrastructure in Idiopathic Inflammatory Myopathies (IIM) has been scarcely explored, especially in Inclusion Body Myositis. The aim of this study was to implement the Scanning Electron Microscopy (SEM) in a small cohort of IIM patients, together with the characterization of immunological profile for a better understanding of the pathophysiology. For immunological profile characterization, we identified the presence of autoantibodies (Ro-52, OJ, EJ, PL7, PL12, SRP, Jo-1, PMScl75, PMScl100, Ku, SAE1, NXP2, MDA5, TIF1γ, Mi-2α, Mi-2ß) and quantified cytokines (IL-1ß, IFN-α2, IFN-γ, TNF-α, IL-6, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33) and chemokines (CCL2, CXCL8). The histological analysis was made by hematoxylin-eosin staining while the muscle fiber ultrastructure was characterized by SEM. We observed changes in the morphology and structure of the muscle fiber according to muscle strength and muscle enzymes. We were able to find and describe muscle fiber ultrastructure with marked irregularities, porosities, disruption in the linearity and integrity of the fascicle, more evident in patients with increased serum levels of muscle enzymes and diminished muscle strength. Despite the scarce reports about the use of SEM as a tool in all clinical phenotypes of IIM, our work provides an excellent opportunity to discuss and reframe the clinical usefulness of SEM in the diagnostic approach of IIM.

Effect of Rituximab Compared with Natalizumab and Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Cohort Study.

The objective of this study was to evaluate the clinical files of patients with RRMS who started rituximab (RTX) compared with a second-line treatment (natalizumab (NTZ) or fingolimod (FTY)). This was a historical cohort study. We compared the effect according to the Expanded Disability Status Scale (EDSS) and the number of relapses in RRMS patients receiving these treatments after a mean period of 12 months. We found a statistically significant difference (p < 0.001) when comparing the EDSS scores and the annual relapse rates of patients receiving RTX with those receiving NTZ or FTY. This study is essential for our clinical practice, since patients with limited treatment options represent a challenge with regard to the management of their medical care. However, clinical trials and prospective studies with long follow-up periods are necessary to provide sufficient evidence on the efficacy of RTX and thus include this treatment in the therapeutic profile of patients with MS.

Suicide Risk in Rheumatoid Arthritis Patients is Associated With Suboptimal Vitamin D Levels.

BACKGROUND/OBJECTIVE: Rheumatoid arthritis (RA) patients might experience anxiety and depressive symptoms. Deficient vitamin D levels may be a trigger for these conditions. The aim of this study was to determine the frequency of depression, anxiety symptoms, and suicidal risk or ideation in patients with RA associated with vitamin D serum levels. METHODS: In this cross-sectional study, we recruited RA patients older than 18 years, classified into 3 groups according to serum vitamin D levels: sufficient, ≥30 ng/mL; insufficient, 20-29 ng/mL; and deficient, <20 ng/mL. Based on the self-reported Plutchik and the Hospital Anxiety and Depression Scale, we evaluated the association of suicidal risk, depression, and anxiety with the vitamin D levels in RA and the Rheumatoid Arthritis Quality-of-Life Questionnaire. RESULTS: We studied 72 patients with RA between January and October 2019. We found an inverse correlation between Plutchik score and suicidal risk with inadequate vitamin D levels, but not with the Hospital Anxiety and Depression Scale. Suicidal ideation was associated with a higher score on the Rheumatoid Arthritis Quality-of-Life Questionnaire. CONCLUSIONS: Despite the high prevalence of depressive and anxiety symptoms in RA patients, a Plutchik low correlation coefficient with inadequate serum levels of vitamin D was found. However, in the analysis of covariance, we were able to find that vitamin D levels remain associated with a reduction of suicide ideation. Further studies are needed to identify a risk profile for early psychological interventions to improve the quality of life in RA patients.

Geographical Latitude Remains as an Important Factor for the Prevalence of Some Myositis Autoantibodies: A Systematic Review.

The idiopathic inflammatory myopathies (IIM) are characterized by muscular weakness, cutaneous manifestations, muscle damage revealed by increase of muscular enzymes, muscle biopsy, electromyography and changes on magnetic resonance imaging. However, the hallmark of these IIM, is the development of myositis specific antibodies (MSA) or myositis associated antibodies (MAA). The theories about their presence in the serum of IIM is not known. Some studies have suggested that some of these MSA, such as anti-Mi-2 increases according to the intensity of UV radiation. There is scarce information about the environmental factors that might contribute in order to be considered as triggering factors as UV radiation might be. In this review, we analyzed the reported prevalence of MSAs and MAAs regarding to their geographical location and the possible relation with UV radiation. We collected the prevalence data of fifteen MSA and thirteen MAA from 22 countries around the world and we were able to observe a difference in prevalence between countries and continents. We found differences in anti-PL7, anti-Ro52, anti-La and anti-Ku prevalence according to UV radiation level. Otherwise, we observed that anti-Mi-2 prevalence increases near to the Equator meanwhile anti-MJ/NXP2 and anti-ARS prevalence had an opposite behavior increasing their prevalence in the geographical locations farther to the Equator. Our results highlighted the importance to include the UV radiation and other environmental factors in IIM studies, in order to clarify its association with MSA and MAA prevalence as well as its possible role in the immunopathogenesis of these diseases.

Presence of anti-TIF-1γ, anti-Ro52, anti-SSA/Ro60 and anti-Su/Ago2 antibodies in breast cancer: a cross-sectional study.

OBJECTIVES: The presence of myositis-specific antibodies (MSA), was recently reported in healthy individuals, cancer patients without myopathy and paraneoplastic rheumatic syndromes. We sought to analyze the frequency of MSA, myositis-associated antibodies (MAA) and autoantibodies related to systemic autoimmune rheumatic diseases (SARD) in breast cancer patients. METHODS: One hundred fifty-two breast cancer patients were enrolled in a cross-sectional study. Clinical information was collected, and autoantibodies tested by immunoprecipitation of an 35S-methionine-labeled K562 cell extract, enzyme-linked immunosorbent assay (ELISA) and Western blot when indicated. All statistical tests were performed using the software statistical package for the social science (SPSS) ver. 19.0 (IBM Inc., NYSE, USA). RESULTS: Autoantibodies associated with SARD: anti-52 kD ribonucleoprotein/tripartite motif-containing 21 (anti-Ro52/TRIM21) was found in 5.9% (9/152), anti-Sjögren syndrome-related antigen A/60 kD ribonucleoprotein antibody (anti-SSA/Ro60) in 3.9% (6/152) and anti-Su antigen/Argonaute 2 antibody (anti-Su/Ago2) in 2.6% (4/152). Meanwhile, anti-transcription intermediary factor-1γ (anti-TIF-1γ, p155/140) antibody was positive in 2 cases and anti-polymyositis/scleroderma antibody was detected in one case. As a whole, 14.47% (22/152) of breast cancer patients showed autoantibodies associated with SARD. These specific autoantibodies were not associated with the presence of rheumatic diseases except one rheumatoid arthritis patient positive for anti-Ro52/TRIM21. CONCLUSIONS: Autoantibodies to TIF-1γ were found in two patients with breast cancer without dermatomyositis (DM). More common specificities were autoantibodies anti-SSA/Ro60, anti-Ro52/TRIM21 and anti-Su/Ago2. More studies are needed in order to establish the biological meaning of the presence of SARD-associated autoantibodies in breast cancer.

Genomic instability in people living with HIV.

The increased life expectancy of people living with HIV (PLWH) receiving antiretroviral treatment (ART) has transformed HIV infection into a chronic disease. However, patients may be at risk of accelerated aging and the accumulation of cellular damage, which may trigger the development of cancer. We evaluated genomic instability in HIV-positive individuals with different viral loads receiving antiretroviral treatment (ART) and in HIV ART-naïve individuals. We included 67 participants divided into four groups: group 1 (n = 24) HIV patients receiving reverse-transcriptase inhibitors (tenofovir/ emtricitabine/ efavirenz and abacavir/ lamivudine/ efavirenz), group 2 (n = 22) HIV patients receiving protease inhibitors combined with other antiretroviral drugs (tenofovir/ emtricitabine with ritonavir/ atazanavir or lopinavir/ ritonavir, and darunavir/ ritonavir/ raltegravir), group 3 (n = 13) HIV ART-naïve patients, and group 4 (n = 8) healthy individuals (controls). Nuclear abnormalities in buccal mucosal samples (micronuclei, binucleated cells, nuclear buds, karyorrhexis, karyolysis, and pyknosis) were quantified. Simultaneously, blood samples were taken to quantify CD4+, CD8+, and HIV viral load. There was a significant age difference between HIV ART-naïve patients and receiving ART groups. Infection time was longer in HIV patients with ART than in ART-naïve patients. There were no differences in sex, smoking, alcohol consumption, or number of micronucleated cells between the study groups. We found higher frequencies of binucleated cells and nuclear buds in HIV patients, HIV ART-naïve, and HIV ART patients compared to the control group. We found a positive correlation between nuclear buds and CD4/CD8 ratio in the HIV ART-naïve group. In conclusion, PLWH showed increased genomic instability. The CD4/CD8 ratio affects the numbers of nuclear buds and binucleated cells. These findings are pertinent to mechanisms of damage and possible strategies to mitigate carcinogenesis in PLWH.

Going Further: Comprehensive Disease Control of Rheumatoid Arthritis, Targeting Cytokines and Chemokines.

OBJECTIVES: Mechanism of action of biological and synthetic disease-modifying antirheumatic drugs (DMARDs) includes the inhibition of specific proinflammatory cytokines. This study aimed to elucidate the cytokines and chemokines inhibited by different treatments (conventional synthetic DMARD [csDMARD], biological and targeted synthetic DMARD) in rheumatoid arthritis (RA). METHODS: Fifty-nine RA patients with low disease activity or remission included in a cross-sectional study were classified by treatment in groups: abatacept, certolizumab, rituximab (RTX), tocilizumab, tofacitinib (TOF), baricitinib (BAR), and csDMARD. Cytokine and chemokine serum levels were measured by LEGENDplex Human Inflammation panel. Quantitative variables were compared using Student t or Mann-Whitney U test as appropriate, whereas qualitative variables were compared using χ2 or Fisher exact test. p < 0.05 was considered significant. RESULTS: Certolizumab, RTX, tocilizumab, and TOF showed that most cytokine pathways inhibited: tumor necrosis factor α, interferon γ, interleukin 1ß (IL-1ß), IL-12, IL-18, and IL-23; in addition, csDMARDs showed a similar inhibition patron except for IL-23. Serum level of tumor necrosis factor α pathway was one of the most inhibited being undetectable in RTX, TOF, and BAR groups. Interleukin 6 was shown to be inhibited by abatacept, RTX, and TOF; however, higher levels were observed in 3 patients treated with tocilizumab. Abatacept, certolizumab, RTX, and TOF downregulated IL-10 in this group of patients but remained detectable in almost half of the subjects, with the highest levels in the BAR group. The active pathways that remained the most were CC chemokine ligand 2, IL-8, IL-17, and IL-33. CONCLUSIONS: Understanding the cytokine chemokine pathways inhibition could help rheumatologists to prescribe a tailored therapy using the arsenal of DMARDs for individualized RA treatment in an evidence-based decision manner.

The Montreal Cognitive Assessment Test: A Useful Tool in Screening of Cognitive Impairment in Patients With Systemic Lupus Erythematosus.

BACKGROUND/OBJECTIVE: Systemic lupus erythematosus (SLE) is an inflammatory, chronic, and multisystemic disease, which may be associated with a wide range of neuropsychiatric manifestations, including cognitive impairment. Cognitive evaluations based on screening tests might identify early SLE-related cognitive alterations. The aim of this study was to evaluate and to compare the efficacy of three screening tests (Montreal Cognitive Assessment [MoCA], Mini Mental State Examination [MMSE], Cognitive Symptom Inventory [CSI]) against the gold standard (neuropsychological battery), in order to identify the most efficient screening test for cognitive impairment in patients with SLE. METHODS: This observational cross-sectional study recruited 44 patients, from August to December 2017, who were diagnosed with SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) Criteria 2012, and had no medical or psychiatric comorbidities. The patients were evaluated using the MoCA, MMSE, CSI, and the gold standard. Spearman's correlation and area under the curve analysis were performed; p < 0.05 was considered significant. RESULTS: The MoCA test showed the highest correspondence with the gold standard (AUC = 99.4%, p < 0.001), sensitivity (84%), and specificity (100%). This was followed by the MMSE (AUC = 92.6%, p < 0.001; sensitivity, 54.8%; specificity, 100%) and the CSI (AUC = 30.6%, p < 0.05; sensitivity, 54.8%; specificity, 30.76%). CONCLUSION: The MoCA is a brief, easily applied screening test that is highly effective for detecting cognitive impairment in SLE patients. It could be useful in clinical follow-up as a tool for early detection of cognitive alterations.

Enalapril Influence on Arterial Stiffness in Rheumatoid Arthritis Women: A Randomized Clinical Trial.

Introduction: Cardiovascular parameters disruption can be found in patients at early stages of rheumatoid arthritis (RA). The primary endpoint of this study was the reduction of arterial stiffness in RA patients without traditional cardiovascular risk factors or previous comorbidities, measured by cardio-ankle vascular index (CAVI) through the enalapril intervention. The secondary endpoints were the enalapril influence on carotid femoral pulse wave velocity (cfPWV), carotid intima media thickness (cIMT), carotid artery distensibility (cDistensibility), Young's incremental elastic modulus (Einc)]. Materials and Methods: Fifty-three patients were enrolled in a clinical, randomized, closed-label trial. The subjects were randomly assigned into two groups: One receiving 5 mg of enalapril (27) or placebo (26), both twice a day. The drug was acquired at Victory Enterprises®. The placebo was kindly provided by the Universidad de Guadalajara (UdeG), as well as the blinding into two groups: A and B. Enalapril and placebo were packed into bottles without labeling. Clinical assessment included a structured questionnaire to gather demographic and clinical variables as well as determination of CAVI, cfPWV, cIMT, carotid artery distensibility and Einc. The whole set of evaluations were analyzed at the baseline and at the end of 12 weeks of intervention. Results: The CAVI measurement at baseline was 7.1 ± 1.4 and increased up to 7.5 ± 1.2 at the end of 12 weeks. Meanwhile, the enalapril group was as follows: 7.4 ± 1.2 and at the of intervention, reduced to 7.1 ± 0.9. A reduction in delta CAVI of 0.21 in the enalapril intervention group was found. In contrast, an increase of 0.39 was observed in the placebo group. The delta CAVI reduction was not influenced by age or peripheral systolic blood pressure (pSBP). Discussion: Enalapril seems to be effective in CAVI reduction in RA patients. The effect of enalapril intervention on arterial stiffness translated to the clinical context might be interpreted as a reduction of 6.4 years of arterial aging. Trial Registration: The protocol was approved by the Institutional Review Board with the register CI-0117 from UdeG, and 0211/18 from Hospital Civil "Dr. Juan I. Menchaca", Secretaría de Salud Jalisco: DGSP/DDI/D.INV.28/18 and retrospectively registered at ClinicalTrials.gov Protocol Registration and Results System: NCT03667131.

Subclinical parameters of arterial stiffness and arteriosclerosis correlate with QRISK3 in systemic lupus erythematosus.

It is well known that cardiovascular diseases (CVD) are a major contributor of death in systemic lupus erythematosus (SLE) as well in other rheumatic illness. In the last decades, there has been a growing development of different methodologies with the purpose of early detection of CVD. OBJECTIVE: The aim of this study is to correlate the usefulness of subclinical parameters of vascular aging and QRISK 3-2017 score for early detection of CVD in SLE. METHODS: Clinical assessment including systemic lupus erythematosus disease activity index (SLEDAI) and systemic lupus international collaborating clinics / american college of rheumatology damage index (SLICC/ACR DI), laboratory measurements, carotid ultrasound examination, carotid intima media thickness (cIMT) measurement, carotid distention and diameter analysis, arterial stiffness measurement measured by tonometry and QRISK 3-2017 were done. All results were analyzed by SPSS 24 software. RESULTS: We observed correlation between QRISK3 and mean cIMT (rs = 0.534, P < 0.001), PWV (rs = 0.474, P < 0.001), cfPWV (rs = 0.569, P < 0.001) and distensibility (rs = -0.420, P = 0.006). Consistent with above, SLE patients in middle and high risk QRISK 3-2017 showed increased arterial stiffness versus low risk group. CONCLUSIONS: We encourage to the rheumatology community to assess cardiovascular risk in SLE patients with QRISK 3-2017 risk calculator as an alternative method at the outpatient clinic along a complete cardiovascular evaluation when appropriate.

Disease duration of rheumatoid arthritis is a predictor of vascular stiffness: a cross-sectional study in patients without known cardiovascular comorbidities: A STROBE-compliant article.

The aim of this study was to analyze the impact of disease duration on carotid to femoral pulse wave velocity (cfPWV) in rheumatoid arthritis (RA) patients without either known traditional cardiovascular risk factors or previous comorbidities.Patients with RA diagnosis attending the rheumatology outpatient clinic of Hospital Civil Juan I. Menchaca, Guadalajara, Mexico, were analyzed. A total of 106 RA patients without known traditional cardiovascular risk factors were selected. All subjects were evaluated for RA disease duration, RA disease activity score on 28 joints (DAS28), serum lipids, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Arterial stiffness was measured as cfPWV by noninvasive tonometry. A multivariate regression model was used to analyze the contribution of RA disease duration and age on cfPWV. cfPWV was positively correlated with age (r = 0.450, P < .001), RA disease duration (r = 0.340, P < .001), total cholesterol (r = 0.312, P = .002), and low density lipoprotein (LDL-c) cholesterol (r = 0.268, P = .012). Patients with a RA disease duration ≥10 years exhibited significantly increased cfPWV compared with patients with disease duration <2 years (8.4 ±â€Š1.8 vs 7.0 ±â€Š0.8) and ≥2 to <10 years (8.4 ±â€Š1.8 vs 7.8 ±â€Š1.3), respectively. Age, RA disease duration, and triglycerides were predictors of cfPWV in multivariate analyses. According to the ß-coefficients, each year of disease duration (ß = 0.072) had a greater impact on cfPWV than age (ß = 0.054).Each year of life with RA contributes to a higher rate of vascular aging or stiffening than a year of life without RA. The cumulative damage provided by RA was most pronounced in patients with disease duration ≥10 years.

Detection of autoantibodies to DSF70/LEDGFp75 in Mexican Hispanics using multiple complementary assay platforms.

PURPOSE: Antinuclear autoantibodies (ANA) targeting the dense fine speckled antigen DFS70, also known as lens epithelium-derived growth factor p75 (LEDGF/p75), are attracting attention due to their low frequency in systemic rheumatic diseases but increased frequency in clinical laboratory referrals and healthy individuals (HI). These ANA specifically recognize the stress protein DFS70/LEDGFp75, implicated in cancer, HIV-AIDS, and inflammation. While their frequency has been investigated in various ethnic populations, there is little information on their frequency among Hispanics/Latinos. In this study, we determined the frequency of anti-DFS70/LEDGFp75 autoantibodies in Mexican Hispanics using multiple detection platforms. METHODS: The frequency of anti-DFS70/LEDGFp75 antibodies was determined in 171 individuals, including 71 dermatomyositis (DM) patients, 47 rheumatoid arthritis (RA) patients, 30 obesity (OB) patients, and 23 HI. Antibody detection was achieved using four complementary assay platforms: indirect immunofluorescence, Western blotting, ELISA, and chemiluminescent immunoassay. RESULTS: We detected relatively low frequencies of anti-DFS70/LEDGFp75 antibodies in patients with DM (1.4%), RA (4.3%), and OB (6.6%), and elevated frequency (17.4%) in HI. A strong concordance between the different antibody detection platforms was observed. CONCLUSIONS: The low frequency of anti-DFS70/LEDGFp75 antibodies in Mexican patients with rheumatic diseases, but relatively higher frequency in HI, is consistent with previous observations with non-Hispanic populations, suggesting that geographic differences or ethnicity do not influence the frequency of these autoantibodies. Our results also highlight the importance of confirmatory assays for the accurate detection of these autoantibodies. Future studies with larger cohorts of healthy Hispanics/Latinos are needed to confirm if their anti-DFS70/LEDGFp75 antibody frequencies are significantly higher than in non-Hispanics.

Disease Activity Score on 28 Joints and Polypharmacy Are Independent Predictors for Health-Related Quality of Life Evaluated by INCAVISA in Patients With Rheumatoid Arthritis.

OBJECTIVE: The aim of this study was to investigate the main factors associated to a diminished health-related quality of life (HRQoL) evaluated by INCAVISA (Health-Related Quality of Life Inventory for Latin American Patients) in patients with rheumatoid arthritis (RA). METHODS: Female, 18 years or older, RA (American College of Rheumatology 1987 criteria and American College of Rheumatology/European League against Rheumatism 2010 criteria) patients who attended the outpatient rheumatology department of the Hospital Civil "Dr. Juan I. Menchaca," Guadalajara, Mexico, matched with healthy controls were included. Patients with any known comorbidities or treatment with antidepressive drugs were excluded. Trained physicians performed the RA clinical evaluation and INCAVISA. All data were analyzed using SPSS 21.0 software (SPSS Inc, Chicago, IL); P < 0.05 was considered statistically significant. RESULTS: Patients with polypharmacy (≥3 drugs) had a lower HRQoL by INCAVISA. The number of drugs, total comorbidities, and DAS-28 (Disease Activity Score on 28 Joints) were negatively correlated with total INCAVISA. In multivariate analysis, DAS-28 and polypharmacy were independent predictors for a negative perception of HRQoL evaluated by INCAVISA in RA patients. CONCLUSIONS: Disease activity and disability secondary to RA have a negative impact in the HRQoL. Other factors such as the number of drugs prescribed to these patients have been shown to be important for the negative perception of their HRQoL evaluated by INCAVISA.

Inverse Relationship of the CMKLR1 Relative Expression and Chemerin Serum Levels in Obesity with Dysmetabolic Phenotype and Insulin Resistance.

BACKGROUND: In obesity there is a subclinical chronic low-grade inflammatory response where insulin resistance (IR) may develop. Chemerin is secreted in white adipose tissue and promotes low-grade inflammatory process, where it expressed CMKLR1 receptor. The role of chemerin and CMKLR1 in inflammatory process secondary to obesity is not defined yet. METHODS: Cross-sectional study with 134 individuals classified as with and without obesity by body mass index (BMI) and IR. Body fat storage measurements and metabolic and inflammatory markers were measured by routine methods. Soluble chemerin and basal levels of insulin by ELISA and relative expression of CMKLR1 were evaluated with qPCR and 2(-ΔΔCT) method. RESULTS: Differences (P < 0.05) were observed between obesity and lean individuals in body fat storage measurements and metabolic-inflammatory markers. Both CMKLR1 expression and chemerin levels were increased in obesity without IR. Soluble chemerin levels correlate with adiposity and metabolic markers (r = 8.8% to 38.5%), P < 0.05. CONCLUSION: The increment of CMKLR1 expression was associated with insulin production. Increased serum levels of chemerin in obesity were observed, favoring a dysmetabolic response. The results observed in this study suggest that both chemerin and CMKLR1 have opposite expression in the context of low-grade inflammatory response manifested in the development of IR.

CCL2 Serum Levels and Adiposity Are Associated with the Polymorphic Phenotypes -2518A on CCL2 and 64ILE on CCR2 in a Mexican Population with Insulin Resistance.

Genetic susceptibility has been described in insulin resistance (IR). Chemokine (C-C motif) ligand-2 (CCL2) is overexpressed in white adipose tissue and is the ligand of C-C motif receptor-2 (CCR2). The CCL2 G-2518A polymorphism is known to regulate gene expression, whereas the physiological effects of the CCR2Val64Ile polymorphism are unknown. The aim of the study is to investigate the relationship between these polymorphisms with soluble CCL2 levels (sCCL2), metabolic markers, and adiposity. In a cross-sectional study we included 380 Mexican-Mestizo individuals, classified with IR according to Stern criteria. Polymorphism was identified using PCR-RFLP/sequence-specific primers. Anthropometrics and metabolic markers were measured by routine methods and adipokines and sCCL2 by ELISA. The CCL2 polymorphism was associated with IR (polymorphic A+ phenotype frequencies were 70.9%, 82.6%, in individuals with and without IR, resp.). Phenotype carriers CCL2 (A+) displayed lower body mass and fat indexes, insulin and HOMA-IR, and higher adiponectin levels. Individuals with IR presented higher sCCL2 compared to individuals without IR and was associated with CCR2 (Ile+) phenotype. The double-polymorphic phenotype carriers (A+/Ile+) exhibited higher sCCL2 than double-wild-type phenotype carriers (A-/Ile-). The present findings suggest that sCCL2 production possibly will be associated with the adiposity and polymorphic phenotypes of CCL2 and CCR2, in Mexican-Mestizos with IR.

The Impact of LEP G-2548A and LEPR Gln223Arg Polymorphisms on Adiposity, Leptin, and Leptin-Receptor Serum Levels in a Mexican Mestizo Population.

The polymorphisms in leptin (LEP G-2548A) and leptin-receptor (LEPR Gln223Arg) seem to influence obesity and lipid metabolism among others. The aim of this study was to investigate the effect of these polymorphisms on adiposity, leptin (sLeptin), and leptin-receptor (sLeptin-receptor) serum concentrations as well as inflammation markers. We included 382 adults originally from Western Mexico. They were genotyped by PCR-RFLP. Obese individuals showed higher sLeptin (58.2 ± 31.35 ng/mL) but lower sLeptin-receptor (12.6 ± 3.74 ng/mL) levels than normal weight ones (17.6 ± 14.62 ng/mL, 17.4 ± 4.62 ng/mL, resp.), P < 0.001. Obese subjects carriers of Arg/Arg genotype had more (P = 0.016) sLeptin-receptor (14.7 ± 4.96 ng/mL) and less (P = 0.004) sLeptin (44.0 ± 28.12 ng/mL) levels than Gln/Gln genotype (11.0 ± 2.92 ng/mL, 80.3 ± 33.24 ng/mL, resp.). Body fat mass was lower (P from 0.003 to 0.045) for A/A (36.5% ± 6.80) or Arg/Arg (36.8% ± 6.82) genotypes with respect to G/G (41.3% ± 5.52) and G/A (41.6% ± 5.61) or Gln/Gln (43.7% ± 4.74) and Gln/Arg (41.0% ± 5.52) genotypes carriers. Our results suggest that LEP -2548A and LEPR 223Arg could be genetic markers of less body fat mass accumulation in obese subjects from Western Mexico.