Cytokine polymorphisms influence treatment outcomes in SLE patients treated with antimalarial drugs

Antimalarial agents have been widely used as disease-modifying antirheumatic drugs in the treatment of systemic lupus erythematosus (SLE) and other rheumatological diseases, although their mechanism of action has not yet been fully defined. It is known, however, that effective response to treatment is variable among patients. Thus, the identification of genetic predictors of treatment response would provide valuable information for therapeutic intervention. The aim of the present study was to analyze the effect of antimalarial treatment on tumor necrosis factor (TNF)α serum levels and evaluate the possible influence of TNFα and IL-10 functional genetic polymorphisms on the response to antimalarial drugs. To this end, TNFα serum levels were quantified in 171 SLE patients and 215 healthy controls by ELISA techniques and polymorphisms at positions -1,082 and -308 of the IL-10 and TNFα gene promoterswere determined by PCR amplification followed by hybridization with fluorescent-labeled allele-specific probes in 192 SLE patients and 343 matched controls. Data were related to clinical features and treatment at the time of sampling and during the course of the disease. Results showed a significantly higher amount of serum TNFα in the entire SLE population compared with controls. However, TNFα serum levels correlated negatively with the use of antimalarial treatment during at least three months before sampling. Patients under single or combined treatment with these drugs had TNFα serum levels similar to healthy controls, whereas untreated patients and those under corticosteroid or immunosuppressive therapies had increased amounts of this cytokine. This suggests, however, that antimalarial-mediated inhibition of TNFα was only significant in patients who were genetically high TNFα or low IL-10 producers. In addition, evaluation of SLE patients administered antimalarial drugs for three or more years who did not require any other specific SLE treatment indicates that patients with the combined genotype low IL-10/high TNFα are the best responders to antimalarial therapy, developing mild disease with a good course under this treatment. In conclusion, we proposed that an antimalarial-mediated downregulation of TNFα levels in SLE patients is influenced by polymorphisms at IL-10 and TNFα promoters. Our results may thus find important clinical application through the identification of patients who are the most likely to benefit from antimalarial therapy

Anti-High-Density Lipoprotein Antibodies and Antioxidant Dysfunction in Immune-Driven Diseases

This work was supported by European Union FEDER funds and “Fondo de Investigación Sanitaria” (FIS, PI12/00523 and PI16/0011; ISCIII, Spain). JR-C is supported by a postdoctoral contract from the “Juan de la Cierva” program (FJCI-2015-23849; MICINN, Spain)

Common and Specific Associations of Anti-SSA/Ro60 and Anti-Ro52/TRIM21 Antibodies in Systemic Lupus Erythematosus

Little information exists about the association of anti-SSA/Ro60 and anti-Ro52/TRIM21 with systemic lupus erytematosus (SLE) features. In this work, we analysed the associations of both anti-Ro reactivities with clinical and immunological manifestations in 141 SLE patients. Photosensitivity and xerophtalmia/xerostomia were found to be positively associated with both anti-SSA/Ro60 (P=0.024 and P=0.019, resp.) and anti-Ro52/TRIM21 (P=0.026 and P=0.022, resp.). In contrast, a negative association was detected regarding anti-phospholipid antibodies, anti-SSA/Ro60 having a stronger effect (P=0.014) than anti-Ro52/TRIM21. Anti-SSA/Ro60 showed a specific positive association with hypocomplementemia (P=0.041), mainly with low C4 levels (P=0.008), whereas anti-Ro52/TRIM21 was found to be positively associated with Raynaud’s phenomenon (P=0.026) and cytopenia (P=0.048) and negatively associated with anti-dsDNA (P=0.013). Lymphocytes are involved in the relationship between anti-Ro52/TRIM21 and cytopenia since positive patients showed lower cell levels than negative patients (P=0.036). In conclusion, anti-SSA/Ro60 and anti-Ro52/TRIM21 showed both common and specific associations in SLE. These data thus increase evidence of the different associations of the two anti-Ro specificities even in a particular disease

Treatment Of A Patient With Thoracolumbar Scoliosis Utilizing A Regional Interdependence Approach Including Components Of The Schroth Method: A Case Report

Background and Purpose: Spinal deformity is a challenging spinal disorder in adults. A scoliotic curve of \u3e10 degrees exists in up to 12% of the population and while surgery is the definitive measure, there is limited evidence to guide non-surgical treatment. This case investigated traditional physical therapy (PT) treatment utilizing a Regional Interdependence Approach (RIA) and components of the Schroth method for a patient with chronic low back pain (CLBP). Case Description: A 66 year old male presented with CLBP, worst upon rising in the AM with (6/10 NPRS). Imaging demonstrated thoracolumbar dextroscoliosis, bilateral foraminal narrowing and associated spondylolisthesis of the fifth lumbar vertebrae. A RIA exam revealed mobility deficits of thoracolumbar spine, instability of L5-S1, and a 1.38” leg length discrepancy. A comprehensive treatment approach was used including lumbar stabilization exercises and postural therapy, including components of the Schroth method. Outcomes: Following 12 weeks, pain improved from 6/10 to 4/105, with the patient reporting no pain when arising from bed. 30-second sit to stand improved from five to eight. Following implementation of a shoe lift visible changes were noted in pelvic symmetry. However, the degree of scoliosis appeared unchanged and no subjective improvements were noted on the Roland-Morris Low Back Pain Questionnaire (RMLBPQ)

Autoantibodies against MHC class I polypeptide-related sequence A are associated with increased risk of concomitant autoimmune diseases in celiac patients

Background: Overexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases. MHC class I polypeptide-related sequence A (MICA) is highly expressed in the enterocytes of patients with celiac disease, which arises in response to gluten. The aim of this study was to investigate anti-MICA antibody formation in patients with celiac disease and its association with other autoimmune processes. Methods: We tested serum samples from 383 patients with celiac disease, obtained before they took up a gluten-free diet, 428 patients with diverse autoimmune diseases, and 200 controls for anti-MICA antibodies. All samples were also tested for anti-endomysium and anti-transglutaminase antibodies. Results: Antibodies against MICA were detected in samples from 41.7% of patients with celiac disease but in only 3.5% of those from controls (P <0.0001) and 8.2% from patients with autoimmune disease (P <0.0001). These antibodies disappeared after the instauration of a gluten-free diet. Anti-MICA antibodies were significantly prevalent in younger patients (P <0.01). Fifty-eight patients with celiac disease (15.1%) presented a concomitant autoimmune disease. Anti-MICA-positive patients had a higher risk of autoimmune disease than MICA antibody-negative patients (P <0.0001; odds ratio = 6.11). The risk was even higher when we also controlled for age (odds ratio = 11.69). Finally, we found that the associated risk of developing additional autoimmune diseases was 16 and 10 times as high in pediatric patients and adults with anti-MICA, respectively, as in those without. Conclusions: The development of anti-MICA antibodies could be related to a gluten-containing diet, and seems to be involved in the development of autoimmune diseases in patients with celiac disease, especially younger ones

Anti-High-Density Lipoprotein Antibodies and Antioxidant Dysfunction in Immune-Driven Diseases

IntroductionImpaired high-density lipoprotein (HDL) levels and antioxidant functionality of HDL, mainly attributed to a decreased paraoxonase-1 (PON1) functionality, have been described in autoimmune conditions. In this setting, a role for humoral response in cardiovascular disease is emerging. This study evaluates the role of immunoglobulin G (IgG) antibodies against HDL and disease-related autoantibodies on HDL dysfunction in immune-driven diseases.MethodsSerum IgG anti-HDL antibodies, PON1 activity, and total antioxidant capacity (TAC) were quantified in 381 patients with different immune-driven diseases [18 mixed connective tissue disease (MCTD), 35 primary Sjögren syndrome (pSS), 38 systemic sclerosis (SSc), 33 ANCA-associated vasculitis (AAV), 60 diabetes mellitus 1, 29 autoimmune B12 deficiency/pernicious anemia, 29 primary biliary cirrhosis, 46 IBD/Crohn, 54 IBD/UC, and 39 celiac disease (CD)] and 138 healthy controls.ResultsIgG anti-HDL antibodies were increased in MCTD, pSS, AAV, and inflammatory bowel disease (IBD) [Crohn and ulcerative colitis (UC)], even after correcting for total IgG levels, but not in organ-specific autoimmune diseases. Anti-HDL antibodies were negatively associated with PON1 activity in MCTD (r = −0.767, p &lt; 0.001) and AAV (r = −0.478, p = 0.005), whereas both anti-HDL and anti-neutrophil cytoplasm antibod levels were related to an impaired PON1 activity and TAC in IBD/UC. In SSc, anti-centromere antibodies correlated PON1 activity. anti-Saccharomyces cerevisiae antibodies levels were negatively associated with PON1 activity (r = −0.257, p = 0.012) and PON1/TAC ratio (r = −0.261, p = 0.009) in IBD/Crohn. HDL dysfunction in CD was only related to anti-transglutaminase levels.ConclusionIgG anti-HDL antibodies and HDL dysfunction are common hallmarks of systemic autoimmunity. Anti-HDL and disease-related autoantibodies account for the HDL antioxidant dysfunction in immune-driven conditions, mainly in systemic autoimmune disorders

Concrete dosage: from trial-and-error to the use of personal computers, which method is better for university students?

[EN] Computer tools have been evolving at an incredible speed in education, especially at the university level. Twenty-five years ago, in university education, there were just beginning to be computer practices based mainly on tools such as Excel in experimental university careers. Today, thanks to the advance in technology, the radiography of universities are very different. Most students come to school daily with their laptops and tablets to college. They are part of the generations called "digital natives.¿ As higher education teachers, we cannot be oblivious to this reality, and we must rethink how to adapt teachings to the daily use of computer technologies. It also means being closer to the procedure these students will follow later when they are professionals in their field. This paper deals with the work done by the Construction Materials unit of the Civil Engineering School to adapt the dosage of concrete to the use of Excel, which was carried out with manual calculations using a calculator until this academic year. Expressly, the use of the Excel spreadsheet was limited to obtaining aggregate granulometric curves from the mixture of several of them so that they were as similar as possible to a series of theoretical curves through the use of equitable adjustments based on the use of a spreadsheet. The teacher's challenge in the classroom is twofold. On the one hand, he has the task of making the students understand the factors and limitations to be considered when carrying out concrete batching. On the other hand, it is to explain the use of a specific tool of the Microsoft "Excel" software to know how a least squares adjustment can be carried out. The present work explains in detail the challenges faced by the teachers, as well as the advantages and disadvantages of moving from a manual procedure (slower, more laborious, and with more room for thought) to a computerized process (more automatic and faster). The latter is how future civil engineers will carry out their work. The advantages of using this type of tool and the main problems detected in the students related to understanding the procedure they are carrying out will be indicated.Gimenez-Carbo, E.; Mozo, C.; Coll Carrillo, H.; Soriano Martinez, L. (2022). Concrete dosage: from trial-and-error to the use of personal computers, which method is better for university students?. IATED. 5138-5142. https://doi.org/10.21125/iceri.2022.12515138514