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.

Exposure to Aggregatibacter actinomycetemcomitans before Symptom Onset and the Risk of Evolving to Rheumatoid Arthritis.

Periodontal disease has been implicated in the pathogenesis of rheumatoid arthritis (RA), an autoimmune disease characterized by immune-mediated synovial damage, and antibodies to citrullinated antigens. Here, we investigate the association between exposure to the periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) and the development of RA. IgM, IgG and IgA antibodies to Aa leukotoxin A (LtxA) were detected by ELISA in plasma from a cohort of Swedish adults at different stages of RA development, from before onset of symptoms to established disease. Patients with early and established RA had increased levels of anti-LtxA IgM compared with matched non-RA controls and periodontally healthy individuals. Logistic regression revealed that anti-LtxA IgM levels were associated with RA during early disease (OR 1.012, 95%CI 1.007, 1.017), which was maintained after adjustment for smoking, anti-CCP antibodies, rheumatoid factor, HLA-DRB1 shared epitope alleles and sex. We found no association between anti-LtxA IgG/IgA antibodies and RA at any stage of disease development. The data support a temporal association between anti-LtxA IgM antibodies and the development of RA, suggesting that a subset of RA patients may have been exposed to Aa around the time of transition from being asymptomatic to become a patient with RA.

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.

Evaluación clínica y ultrasonográfica de la glándula tiroides en pacientes con artritis reumatoide.

Introducción: Los pacientes con artritis reumatoide pueden desarrollar enfermedad tiroidea autoinmune (ETA), cuyo diagnóstico clínico puede ser difícil debido a que ambas comparten síntomas como artralgias, mialgias, rigidez matutina o fatiga. Objetivo: Determinar la prevalencia de ETA en pacientes con artritis reumatoide. Método: Estudio transversal que incluyó 78 pacientes con artritis reumatoide y 81 controles clínicamente sanos pareados por edad y sexo. A ambos grupos se realizó cuantificación de anticuerpos antitiroideos, pruebas de función tiroidea, ultrasonido y biopsia de glándula tiroides cuando la puntuación de Thyroid Imaging Reporting and Data System (TIRADS) fue ≥ 4. Resultados: 24.4 % de los pacientes con artritis reumatoide presentó hipotiroidismo (p = 0.003) y altos títulos de anticuerpos antitiroideos versus controles clínicamente sanos; 53 % de los ultrasonidos tiroideos resultó normal en pacientes hipotiroideos; en pacientes con artritis reumatoide positivos para anticuerpos antitiroideos se encontró perfusión incrementada en 40 %. Los casos clasificados como TIRADS 4 fueron enviados a aspiración, con resultado histopatológico benigno. Conclusiones: Se demostró el valor clínico agregado de la evaluación tiroidea en pacientes con artritis reumatoide, conforme a la prevalencia de hipotiroidismo subclínico, positividad de anticuerpos antitiroideos y anomalías en el ultrasonido independientes de la función tiroidea normal o alterada. Introduction: Patients with rheumatoid arthritis can develop autoimmune thyroid disease (ATD), the clinical diagnosis of which can be difficult because both entities share symptoms such as arthralgia, myalgia, morning stiffness or fatigue. Objective: To determine the prevalence of ATD in patients with rheumatoid arthritis. Method: Cross-sectional study that included 78 patients with rheumatoid arthritis and 81 clinically healthy controls matched by age and gender. Both groups underwent anti-thyroid antibodies quantification, thyroid function tests, thyroid ultrasound and thyroid gland biopsy when the Thyroid Imaging Reporting and Data System (TIRADS) score was ≥ 4. Results: Hypothyroidism was found in 24.4% of patients with rheumatoid arthritis (p = 0.003), as well as high titers of anti-thyroid antibodies versus clinically healthy controls; 53% of thyroid ultrasounds were normal in hypothyroid patients, and increased perfusion was found in 40% of rheumatoid arthritis patients who tested positive for anti-thyroid antibodies. Cases classified as TIRADS 4 underwent aspiration with benign histopathological results. Conclusions: Thyroid assessment added clinical value was demonstrated in patients with rheumatoid arthritis, according to the prevalence of subclinical hypothyroidism, anti-thyroid antibodies positivity and ultrasound abnormalities, regardless of normal or altered thyroid function.

Loss of CD28 within CD4+ T cell subsets from cervical cancer patients is accompanied by the acquisition of intracellular perforin, and is further enhanced by NKG2D expression.

CD28 is well characterized as an essential co-stimulatory receptor critical for activation, proliferation and survival processes in CD4+ T cells. Populations of CD4+CD28null T cells, with apparently contradictory physiological roles, have recently been reported, along with the co-expression of the NK activating receptor NKG2D, in autoimmune diseases and chronic viral inflammation. Paradoxically, studies in cancer suggest that an expanded CD4+NKG2D+ population may be armed with immunosuppressive properties. We have recently reported the existence of two separate CD4+NKG2D+ T cell populations, which were defined by the presence or absence of the co-stimulatory molecule CD28, with the CD4+CD28nullNKG2D+ population more frequently observed in women with cervical cancer. This has led to the present effort to further characterize this population and to determine if the loss of CD28 influences the acquisition of cytotoxic or regulatory markers. In the present work, a multicolor flow cytometry protocol was used to analyze the expression of cytotoxic and immunoregulatory markers on circulating CD4+ T cells characterized by the presence or absence of CD28 and NKG2D in patients with invasive cervical carcinoma and age/gender-matched healthy controls. A noticeable expansion of CD4+CD28null cells, many of them NKG2D+, were observed in selected cervical cancer samples. This CD4+CD28null T cell population was characterized by a lack of immunoregulatory markers, as well as very low basal levels of intracellular IFN-γ, TNF-α, TGF-ß, and IL-10. Intracellular perforin, however, was found to be significantly increased in this CD4+CD28null population, and increases in the mean fluorescence intensity of perforin were found to be enhanced by the presence of NKG2D. In conclusion, our data provide the first evidence of a strict link between the absence of CD28 and the expression of perforin, which is likewise enhanced by the expression of NKG2D, within selected CD4+ T cells from cervical cancer patients.

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.

Low CD36 and LOX-1 Levels and CD36 Gene Subexpression Are Associated with Metabolic Dysregulation in Older Individuals with Abdominal Obesity.

Background. Obesity study in the context of scavenger receptors has been linked to atherosclerosis. CD36 and LOX-1 are important, since they have been associated with atherogenic and metabolic disease but not fat redistribution. The aim of our study was to determinate the association between CD36 and LOX-1 in presence of age and abdominal obesity. Methods. This is a cross-sectional study that included 151 healthy individuals, clinically and anthropometrically classified into two groups by age (<30 and ≥30 years old) and abdominal obesity (according to World Health Organization guidelines). We excluded individuals with any chronic and metabolic illness, use of medication, or smoking. Fasting blood samples were taken to perform determination of CD36 mRNA expression by real-time PCR, lipid profile and metabolic and low grade inflammation markers by routine methods, and soluble scavenger receptors (CD36 and LOX-1) by ELISA. Results. Individuals ≥30 years old with abdominal obesity presented high atherogenic index, lower soluble scavenger receptor levels, and subexpression of CD36 mRNA (54% less). On the other hand, individuals <30 years old with abdominal adiposity presented higher levels in the same parameters, except LOX-1 soluble levels. Conclusion. In this study, individuals over 30 years of age presented low soluble scavenger receptors levels pattern and CD36 gene subexpression, which suggest the chronic metabolic dysregulation in abdominal obesity.

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.

UNLABELLED: 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.

Low levels of CD36 in peripheral blood monocytes in subclinical atherosclerosis in rheumatoid arthritis: a cross-sectional study in a Mexican population.

UNLABELLED: Patients with rheumatoid arthritis (RA) have a higher risk for atherosclerosis. There is no clinical information about scavenger receptor CD36 and the development of subclinical atherosclerosis in patients with RA. The aim of this study was to evaluate the association between membrane expression of CD36 in peripheral blood mononuclear cells (PBMC) and carotid intima-media thickness (cIMT) in patients with RA. METHODS: We included 67 patients with RA from the Rheumatology Department of Hospital Civil "Dr. Juan I. Menchaca," Guadalajara, Jalisco, Mexico. We evaluated the cIMT, considering subclinical atherosclerosis when >0.6 mm. Since our main objective was to associate the membrane expression of CD36 with subclinical atherosclerosis, other molecules related with cardiovascular risk such as ox-LDL, IL-6, and TNFα were tested. RESULTS: We found low CD36 membrane expression in PBMC from RA patients with subclinical atherosclerosis (P < 0.001). CD36 mean fluorescence intensity had negative correlations with cIMT (r = -0.578, P < 0.001), ox-LDL (r = -0.427, P = 0.05), TNFα (r = -0.729, P < 0.001), and IL-6 (r = -0.822, P < 0.001). CONCLUSION: RA patients with subclinical atherosclerosis showed low membrane expression of CD36 in PBMC and increased serum proinflammatory cytokines. Further studies are needed to clarify the regulation of CD36 in RA.