Biomarkers in Systemic Lupus Erythematosus along with Metabolic Syndrome.

Metabolic syndrome (MetS) is a group of physiological abnormalities characterized by obesity, insulin resistance (IR), and hypertriglyceridemia, which carry the risk of developing cardiovascular disease (CVD) and type 2 diabetes (T2D). Immune and metabolic alterations have been observed in MetS and are associated with autoimmune development. Systemic lupus erythematosus (SLE) is an autoimmune disease caused by a complex interaction of environmental, hormonal, and genetic factors and hyperactivation of immune cells. Patients with SLE have a high prevalence of MetS, in which elevated CVD is observed. Among the efforts of multidisciplinary healthcare teams to make an early diagnosis, a wide variety of factors have been considered and associated with the generation of biomarkers. This review aimed to elucidate some primary biomarkers and propose a set of assessments to improve the projection of the diagnosis and evolution of patients. These biomarkers include metabolic profiles, cytokines, cardiovascular tests, and microRNAs (miRs), which have been observed to be dysregulated in these patients and associated with outcomes.

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.

Distribution and characteristics of the certification of rheumatologists in Mexico.

OBJECTIVE: Describe the distribution of adult and pediatric rheumatologists with current certification in Mexico and the factors associated with this distribution. METHODS: The databases of the Mexican Council of Rheumatology and the Mexican College of Rheumatology for 2020 were reviewed. The rate of rheumatologists per 100,000 inhabitants by state of the Mexican Republic was calculated. To find out the number of inhabitants by state, the results of the 2020 population census of the National Institute of Statistics and Geography were consulted. The number of rheumatologists with current certification by state, age, and sex was analyzed. RESULTS: In Mexico, there are 1002 registered adult rheumatologists with a mean age of 48.12 ±â€¯13 years. The male gender prevailed with a ratio of 1.18:1. Ninety-four pediatric rheumatologists were identified with a mean age of 42.25 ±â€¯10.4 years, with a predominance of the female gender with a ratio of 2.2:1. In Mexico City and Jalisco, more than one rheumatologist/100,000 inhabitants were reported in the specialty of adults and only in Mexico City in pediatrics. The current certification is 65%-70% on average and the factors associated with a higher prevalence were younger age, female gender and geographic location. CONCLUSIONS: There is a shortage of rheumatologists in Mexico and in the pediatric area there are underserved regions. It is important that health policies apply measures that allow a more balanced and efficient regionalization of this specialty. Although most rheumatologists have current certification, it is necessary to establish strategies to increase this proportion.

Osteopontin: A Bone-Derived Protein Involved in Rheumatoid Arthritis and Osteoarthritis Immunopathology.

Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) glycoprotein that plays a critical role in bone remodeling. Therefore, it is an effector molecule that promotes joint and cartilage destruction observed in clinical studies, in vitro assays, and animal models of RA and OA. Since OPN undergoes multiple modifications, including posttranslational changes, proteolytic cleavage, and binding to a wide range of receptors, the mechanisms by which it produces its effects, in some cases, remain unclear. Although there is strong evidence that OPN contributes significantly to the immunopathology of RA and OA when considering it as a common denominator molecule, some experimental trial results argue for its protective role in rheumatic diseases. Elucidating in detail OPN involvement in bone and cartilage degeneration is of interest to the field of rheumatology. This review aims to provide evidence of the OPN's multifaceted role in promoting joint and cartilage destruction and propose it as a common denominator of AR and OA immunopathology.

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.

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.

Osteopontin: another piece in the systemic lupus erythematosus immunopathology puzzle.

Osteopontin (OPN) is a phosphoglycoprotein involved in bone remodelling, wound healing, cell adhesion, tissue remodelling, and immune response that is distributed widely in normal adult tissues. OPN biological activity is regulated by thrombin and matrix metalloproteinases (MMPs) cleavage, where the full-length (OPN-FL) protein and the cleaved OPN-N are associated with autoimmune diseases such as systemic lupus erythematosus (SLE). OPN overexpression has been associated with a predisposition to SLE and bad prognosis since OPN could mediate a sustained polyclonal B cell activation that besides to intracellular OPN (iOPN) form, promote the T follicular helper (TFH) cells and enhance anti-nuclear antibody production. Currently, the role of OPN in lupus nephritis (LN) has been reported and extensively studied; however, no data are available about the potential mechanism of OPN in neuropsychiatric SLE (NPSLE). In this review, we highlighted the contribution of OPN and iOPN in LN and NPSLE immunopathology.

Contribution of rs3211938 polymorphism at CD36 to glucose levels, oxidized low-density lipoproteins, insulin resistance, and body mass index in Mexican mestizos with type-2 diabetes from western Mexico.

INTRODUCTION: Background: type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance (IR), and abnormal fatty acid metabolism in which the CD36 receptor has been implicated in glucose and lipid dysregulation. Objective: to evaluate the contribution of polymorphism CD36 rs3211938 to metabolic profile in T2DM Mexican mestizos from western Mexico. Methods: we included 115 individuals classified as non-T2DM (NT2DM) adults and T2DM patients. Polymorphism CD36 rs3211938 was assessed by PCR-RFLP. Anthropometric and metabolic markers were measured by routine methods, and insulin and oxidized LDL (ox-LDL) were measured by ELISA. Results: the distribution of genotypes between NT2DM and T2DM patients was different (p < 0.001), as was the allele frequency (p = 0.002). NT2DM TG carriers showed the lowest levels of basal insulin and HOMA-IR index in comparison with TT carriers (p < 0.05 and p < 0.05, respectively). In the T2DM group TG carriers showed high BMI, WHR, and weight values (p = 0.001; p ≤ 0.05 and p < 0.05, respectively), and the highest levels of basal glucose, HDL-cholesterol, ox-LDL, and HOMA-IR (p < 0.001; p < 0.001; p < 0.001, and p = 0.001, respectively) in comparison with diabetic TT carriers. Conclusion: the CD36 rs3211938 TG genotype is associated with high levels of glucose, ox-LDL, HDL-cholesterol, and IR, and with increased BMI in Mexican mestizo T2DM patients from western Mexico.

INTRODUCCIÓN: Antecedentes: la diabetes mellitus de tipo 2 (DMT2) es un trastorno metabólico crónico caracterizado por hiperglucemia, resistencia a la insulina (RI) y metabolismo anormal de ácidos grasos en el que se ha implicado el receptor CD36 en la disregulación de la glucosa y los lípidos. Objetivo: evaluar la contribución del polimorfismo CD36 rs3211938 al perfil metabólico en individuos mestizos mexicanos con DMT2 del occidente de México. Métodos: se incluyeron 115 individuos clasificados en adultos sin DMT2 (NDMT2) y pacientes con DMT2. El polimorfismo CD36 rs3211938 se identificó mediante PCR-RFLP. Las mediciones antropométricas y metabólicas se realizaron mediante métodos de rutina y la insulina y las LDL-oxidadas (LDL-ox) se midieron por ELISA. Resultados: las distribuciones de los genotipos entre los pacientes NDMT2 y DMT2 fueron diferentes (p < 0,001), así como la frecuencia alélica (p = 0,002). Los individuos NDMT2 portadores del genotipo TG mostraron niveles más bajos de insulina basal e índice HOMA-IR en comparación con los portadores del genotipo TT (p < 0,05 y p < 0,05, respectivamente). En el grupo DMT2, los portadores del genotipo TG presentaron valores elevados de índice de masa corporal (IMC), índice cintura-cadera (ICC) y peso (p = 0,001; p < 0,05 y p < 0,05, respectivamente) y niveles más altos de glucosa basal, HDL-colesterol, LDL-ox y HOMA-IR (p < 0,001; p < 0,001; p < 0,001 y p = 0,001, respectivamente) en comparación con los portadores del genotipo TT. Conclusión: el genotipo TG del polimorfismo CD36 rs3211938 se asocia a altos niveles de glucosa, ox-LDL, HDL-colesterol y RI, y a aumentos del IMC en los pacientes mestizos mexicanos con DMT2 del occidente de México.

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.

Adenovirus Biodistribution is Modified in Sensitive Animals Compared to Naïve Animals.

Pre-existing immune response against adenovirus could diminish transgene expression efficiency when Ad is employed in humans as gene therapy vector. We previously used Ad-hΔuPA (Recombinant adenovirus expressing human urokinase-type plasminogen activator) as antifibrotic gene therapy in cirrhosis models and demonstrated its effectiveness. As a further clinical approach, transient Cyclosporine A (CsA) immunosuppression was induced in cirrhotic animals to determine whether Ad-hΔuPA administration retained efficacy. Adenovirus sensitization was achieved by systemic administration of non-therapeutic Ad-ßGal (Recombinant adenovirus expressing beta-galactosidase) after 4 weeks of intraperitoneal carbon tetrachloride (CCl4) regimen. Cirrhosis induction continued up to 8 weeks. At the end of CCl4 intoxication, immunosuppression was achieved with three CsA doses (40 mg/kg) as follows: 24 h before administration of Ad-hΔuPA, at the moment of Ad-hΔuPA injection and finally, 24 h after Ad-hΔuPA inoculation. At 2 and 72 h after Ad-hΔuPA injection, animals were sacrificed. Liver, spleen, lung, kidney, heart, brain, and testis were analyzed for Ad-biodistribution and transgene expression. In naïve animals, Ad-hΔuPA genomes prevailed in liver and spleen, while Ad-sensitized rats showed Ad genomes also in their kidney and heart. Cirrhosis and Ad preimmunization status notably diminished transgene liver expression compared to healthy livers. CsA immunosuppression in cirrhotic animals has no effect on Ad-hΔuPA biodistribution, but increments survival.

IgG Anti-ghrelin Immune Complexes Are Increased in Rheumatoid Arthritis Patients Under Biologic Therapy and Are Related to Clinical and Metabolic Markers.

Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with increased risk of cardiovascular disease and metabolic alterations. The mechanisms underlying these alterations remain unclear. Ghrelin is a gastrointestinal hormone with potent effects on food intake, body weight, metabolism, and immune response. Recent studies reported the presence of anti-ghrelin autoantibodies in healthy subjects and the levels and affinity of these autoantibodies were altered in anorectic and obese individuals. In this cross-sectional study we analyzed anti-ghrelin autoantibodies in RA patients and evaluated its relationship with clinical, body-composition and metabolic parameters. Clinical measurements of RA patients included the disease activity score-28 (DAS-28), inflammatory biomarkers, autoantibodies (RF and anti-CCP), body composition, glucose and lipid profile. Serum ghrelin levels were measured by enzyme-linked immunosorbent assay (ELISA). Free and total anti-ghrelin autoantibodies quantification (IgG and IgA isotypes) was performed by in-house ELISA. RA patients had lower IgG anti-ghrelin autoantibodies levels and higher immune complexes percentage (IgG+ghrelin) compared to the control group, while the IgA anti-ghrelin autoantibodies showed no significant differences. In the bivariate analysis, the percentage of IgG anti-ghrelin immune complexes positively correlated with BMI and ghrelin whereas in the multivariate regression model, the variables associated were DAS-28, body weight, visceral fat, LDL-C and TG (R 2 = 0.72). The percentage of IgA anti-ghrelin immune complexes positively correlated with RF and anti-CCP and the multivariate regression model showed an association with RF and body fat percentage (R 2 = 0.22). Our study shows an increased percentage of IgG anti-ghrelin immune complexes in RA patients despite ghrelin levels were similar in both groups, suggesting an increase in the affinity of these autoantibodies toward ghrelin. The associations found in the multiple regression analysis for anti-ghrelin immune complexes support the previously reported functions of these natural autoantibodies as carriers and modulators of the stability and physiological effect of the hormone. However, in RA both the disease activity and the RF appear to influence the formation of these anti-ghrelin immune complexes.

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.

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.

Potential Chronotherapeutic Optimization of Antimalarials in Systemic Lupus Erythematosus: Is Toll-Like Receptor 9 Expression Dependent on the Circadian Cycle in Humans?

Toll-like receptor 9 (TLR9) belongs to the group of endosomal receptors of the innate immune system with the ability to recognize hypomethylated CpG sequences from DNA. There is scarce information about TLR9 expression and its association with the circadian cycle (CC). Different patterns of TLR9 expression are regulated by the CC in mice, with an elevated expression at Zeitgeber time 19 (1:00 a.m.); nevertheless, we still need to corroborate this in humans. In systemic lupus erythematosus (SLE), the inhibitory effect of chloroquine (CQ) on TLR9 is limited. TLR9 activation has been associated with the presence of some autoantibodies: anti-Sm/RNP, anti-histone, anti-Ro, anti-La, and anti-double-stranded DNA. Treatment with CQ for SLE has been proven to be useful, in part by interfering with HLA-antigen coupling and with TLR9 ligand recognition. Studies have shown that TLR9 inhibitors such as antimalarial drugs are able to mask TLR9-binding sites on nucleic acids. The data presented here provide the basic information that could be useful for other clinical researchers to design studies that will have an impact in achieving a chronotherapeutic effect by defining the ideal time for CQ administration in SLE patients, consequently reducing the pathological effects that follow the activation of TLR9.

Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis.

INTRODUCTION: There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis. OBJECTIVE: The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN). METHODS: In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN. RESULTS: We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 µg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02). Instead, leptin was not associated with LN. CONCLUSION: These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

Prolactin has a pathogenic role in systemic lupus erythematosus.

Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituitary sites including the immune cells. Prolactin (PRL) participates in innate and adaptive immune response. PRL stimulates the immune cells by binding to receptor (PRL-R). Binding of PRL to its receptor activates the Janus kinase-signal transducer (JAK-STAT). Activation of these cascades results in endpoints such as immunoestimulator and immunosupressor action. Prolactin belongs to the network of immune-neuroendocrine interaction. Hyperprolactinemia has been found in patients with systemic lupus erythematosus (SLE), and new evidence has confirmed a significant correlation between serum PRL levels and disease activity. PRL participates in activation of SLE during pregnancy and in pathogenesis of lupus nephritis, neuropsychiatric, serosal, hematologic, articular, and cutaneous involvement. Hyperprolactinemia was associated with increase IgG concentrations, anti-DNA antibodies, immune complex, glomerulonephritis, and accelerated mortality in murine lupus. Bromocriptine, a dopamine analog that suppresses PRL secretion, was associated with decreased lupus activity, prolonged lifespan, and restoration of immune competence in experimental model. In clinical trials, bromocriptine and derivative drugs showed beneficial therapeutic effect in treating human lupus, including pregnancy. Taken together, clinical and experimental results leave little doubt that PRL indeed contributes to the pathogenesis and clinical expression of SLE.

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.