Study of the diagnostic efficiency of anti-ZnT8 autoantibodies for type 1 diabetes in pediatric patients.

OBJECTIVE: Zinc transporter 8 autoantibodies (ZNt8A) are 1 of the 4 main autoantibodies used for the diagnosis of type 1 diabetes (T1D), with glutamic acid decarboxylase autoantibodies (GADA), islet antigen-2 autoantibodies (IA-2A), and insulin autoantibodies (IAA). The objective of this study is to evaluate the diagnostic efficiency of these autoantibodies for the diagnosis of T1D in pediatric patients. METHODS: A retrospective analysis of patients under 16 years of age with suspected T1D was made between June 2020 and January 2021. A total of 80 patients were included in the study, with 1 sample per patient. Subjects were classified according to diagnosis. RESULTS: Of the subjects included in the study, 50 developed T1D. The diagnostic efficacy was IA-2A (cutoff ≥ 28 U/L) sensitivity 0.26 (95% CI: 0.14-0.38) and specificity 0.97 (95% CI: 0.79-1.0); GADA (cutoff ≥ 17 U/mL) sensitivity 0.40 (95% CI: 0.26-0.54) and specificity 0.87 (95% CI: 0.75-0.99); ZnT8A (cut off ≥ 15 U/L) sensitivity 0.62 (95% CI: 0.49-0.75) and specificity 0.97 (95% CI: 0.90-1.0). ZnT8A obtained the most significantly global diagnostic accuracy (0.75), and GADA with ZnT8A showed the highest correlation. CONCLUSION: The results obtained indicate a higher efficiency of anti-ZnT8 autoantibodies for the diagnosis of T1D in pediatric patients. Clinical efficiency of diabetic autoantibodies is method and assay dependent and influences combined diagnostic strategies.

The HLA-DQA1*05 genotype does not influence the clinical response to ustekinumab and vedolizumab.

BACKGROUND: the success of strategies with earlier anti-TNF drugs for the treatment of inflammatory bowel disease (IBD) have been shadowed by the development of anti-drug antibodies that reduce their effectiveness. The HLA-DQA1*05 allele has been shown to increase the risk of immunogenicity to anti-TNF drugs by approximately two-fold. The negative impact of this allele has not been fully investigated for newer biotherapies. OBJECTIVE: whether the presence of the HLA-DQA1*05 allele is associated with a reduction of response to ustekinumab and vedolizumab was investigated. MATERIAL AND METHODS: the impact of HLA-DQA1*05 on disease activity in 93 patients with IBD, treated with ustekinumab (n = 39) or vedolizumab (n = 54) was investigated in a retrospective cohort study. Treatment response and remission was assessed at 6 and 12 months for ustekinumab, and up to 18 and 24 months for vedolizumab, using Harvey-Bradshaw index (Crohn's disease) and Mayo score (ulcerative colitis). RESULTS: the HLA-DQA1*05 allele was found in 35.9 % and 38.9 % of patients treated with ustekinumab and vedolizumab, respectively. Clinical response was not affected by the presence of the HLA-DQA1*05 allele for both treatment groups. CONCLUSIONS: in contrast to anti-TNF drugs, HLA-DQA1*05 presence does not correlate with the decreased response to ustekinumab or vedolizumab.

Evaluation of health outcomes after the implementation of rotational thromboelastometry in patients undergoing cardiac surgery.

BACKGROUND: Viscoelastic tests (rotational thromboelastometry, ROTEM®), together with the implementation of a specific algorithm for coagulation management in cardiac surgery, enable perioperative coagulopathy to be better controlled. METHODS: Retrospective cohort study including 675 patients who underwent cardiac surgery with cardiopulmonary bypass. The incidence of allogeneic blood transfusions and clinical postoperative complications were analyzed before and after ROTEM® implementation. RESULTS: Following viscoelastic testing and the implementation of a specific algorithm for coagulation management, the incidence of any allogeneic blood transfusion decreased (41.4% vs 31.9%, p = .026) during the perioperative period. In the group monitored with ROTEM®, decreased incidence of transfusion was observed for packed red blood cells (31.3% vs 19.8%, p = .002), fresh frozen plasma (9.8% vs 3.8%, p = .008), prothrombin complex concentrate administration (0.9% vs 0.3%, p = .599) and activated recombinant factor VII (0.3% vs 0.0%, p = .603). Increased incidence was observed for platelet transfusion (4.8% vs 6.8%, p = .530) and fibrinogen concentrate (0.9% vs 3.5%, p = .066), tranexamic acid (0.0% vs 0.6%, p = .370) and protamine administration (0.6% vs 0.9%, p = .908). Similar results were observed in the postoperative period, but with a decreased incidence of platelet transfusion (4.8% vs 3.8%, p = .813). In addition, statistically significant reductions were detected in the incidence of postoperative bleeding (9.5% vs 5.3%, p = .037), surgical reexploration (6.0% vs 2.9%, p = .035), and length of Intensive Care Unit (ICU) stay (6.0 days vs 5.3 days, p = .026). CONCLUSIONS: The monitoring of hemostasis by ROTEM® in cardiac surgery, was associated with decreased incidence of allogeneic blood transfusion, clinical hematologic postoperative complications and lengths of ICU stay.

Effects of the COVID-19 pandemic on the activity of clinical laboratories in Spain, evolution in the 2019-2021 period.

Objectives: To assess the impact of the COVID-19 pandemic on the activity of clinical laboratories in Spain. Methods: A descriptive, observational, retrospective, multicenter study. Results: Between March and December 2020, there was a statistically significant decrease in the number of test requests (-17.7%, p=<0.001) and total tests performed (-18.3%, p<0.001) with respect to the same period in 2019. A decrease was observed in the number of requests from primary care (-37.4%) (p<0.001) and in the number of foecal occult blood (-45.8%); qualitative urine (-30.1%); PSA (-28.5%); TSH (-27.8%); total cholesterol (-27.2%) and HbA1c (-24.7%) tests performed, p<0.001. A significant increase was found in the number of requests from ICUs (76.6%, p<0.001) and number of IL-6 (+22,350.9), D-dimer (+617.2%), troponin (+46.8%) and arterial blood gas (+3.9%) tests carried out, p<0.001. During the first months of 2021, there were significant changes in the number of requests for qualitative urine (-8.7%, p<0.001), PSA (-6.3%, p=0.009), IL-6 (+66,269.2, p<0.001), D-dimer (+603.6%, p<0.001), troponin (+28.7%, p<0.001), arterial blood gas (+26,2%, p=0.014) and ferritin (+16.0%, p=0.002) tests performed. Conclusions: There were changes in the origin and number of test requested to clinical laboratories in Spain. The number of requests for the evaluation and monitoring of COVID-19 patients increased, whereas requests for the control of non-COVID patients and for population screening decreased. Long-term analysis reveals that the volume of tests performed for the control of chronic diseases returned to normal over time, whereas the increase observed in the volume of tests performed for the management of COVID-19 patients is maintained.

Comparison of the analytical and clinical performances of two different routine testing protocols for antinuclear antibody screening.

BACKGROUND: The diagnosis of systemic autoimmune rheumatic diseases (SARD) is based on the detection of serum antinuclear antibodies (ANA) for which indirect immunofluorescence (IIF) is the golden standard. New solid-phase immunoassays have been developed to be used alone or in combination with the detection of extractable antinuclear antibodies (ENA) to improve SARD diagnosis. The purpose of this study was to compare the clinical performances of different ANA screening methods alone or in combination with ENA screening methods for SARD diagnosis. METHODS: A total of 323 patients were screened for ANA by IIF, EliA™ CTD Screen, and ELISA methods. Agreements were calculated between the methods. Then, EliA™ CTD Screen positive samples were screened for ENA by line immunoassay (LIA) and fluorescence enzyme immunoassay (FEIA). RESULTS: The diagnostic accuracy of EliA™ CTD Screen (79% sensitivity and 91% specificity) was better than that of ELISA or IIF. The combination of EliA™ CTD plus IIF had the highest sensitivity (93%). ENA determination revealed that Ro52 and Ro60 were the most prevalent specificities. The use of IIF alone was not able of detecting up to 36% of samples positive for Ro52, and 41% for Ro60. CONCLUSIONS: EliA™ CTD Screen has a better diagnostic performance when compared to IIF and ELISA. The combined use of EliA™ CTD Screen and IIF clearly improves the rate and accuracy of SARD diagnosis. The use of EliA™ CTD Screen as first-line screening technique allows the detection of antibodies, which could not be detected by IIF alone.

Update and clinical management of anti-DNA auto-antibodies.

Anti-deoxyribonucleic acid (DNA) antibodies in the clinical laboratory are intimately linked to the diagnosis and monitoring of systemic lupus erythematosus (SLE); however, the characteristics of the analytical methods and the properties of the antibodies themselves are heterogeneous. To review the definition and properties of anti-double-stranded anti-DNA (anti-dsDNA) antibodies, the adequacy of analytical methods, and the clinical requirements for this biomarker. Through PubMed we searched the existing literature with the terms anti-dsDNA, editorial, review, guideline, meta-analysis and SLE. The last search, anti-dsDNA and SLE restricted to the last two years. Information was expanded through related articles and those published in official state bodies related to anti-dsDNA and SLE. Clinical laboratory methods for anti-dsDNA analysis and their characteristics are analyze. The clinical utility of anti-dsDNA in its diagnostic, clinical association and follow-up aspects of SLE is reviewed. There is wide variability in analytical methods and deficits in standardization persist. They are part of the current SLE classification criteria and are used as markers in the follow-up of the disease. Their diagnostic usefulness improves when they are determined in antinuclear antibody (ANA)-positive patients. In follow-up, quantification is of interest, preferably with the same analytical method (given the deficits in standardization).

Screening for Gestational Diabetes Mellitus by Measuring Glycated Hemoglobin Can Reduce the Use of the Glucose Challenge Test.

BACKGROUND: Physiological changes during pregnancy, such as dilutional anemia and a reduced half-life of red blood cells, have prevented the use of glycated Hb (HbA1c) as a biomarker for gestational diabetes mellitus (GDM). Nevertheless, increasing evidence supports the use of HbA1c in GDM diagnostic strategies.We studied HbA1c as a biomarker of GDM and its possible use as a screening test to avoid the use of the glucose challenge test (GCT). METHODS: This case-control study involved 607 pregnant women between the 24th and 28th week of gestation. HbA1c level was determined, and GDM was diagnosed according to the National Diabetes Data Group criteria. The area under the ROC curve (AUC) was determined; two low and two high cut-off points were established to rule out GDM and classify high-risk pregnant women, respectively. For each cut-off, sensitivity (S), specificity (SP), and total number and percentage of GCTs avoided were determined. RESULTS: The AUC for HbA1c diagnostic performance was 0.68 (95% confidence interval 0.57-0.79). Using 4.6% HbA1c (27 mmol/mol) as the lower cut-off (S=100%), 14% of participants could avoid the GCT. Using 5.5% HbA1c (36 mmol/mol) as the upper cut-off (SP =94.5%), 6% of participants would be considered at high risk. CONCLUSIONS: HbA1c can be used as a screening test prior to the GCT, thereby reducing the need for the GCT among pregnant women at a low risk of GDM.

Coexistence of anti-Jo1 and anti-signal recognition particle antibodies in a polymyositis patient. / Coexistencia de anticuerpos anti-histidil-tRNA-sintetasa y anti-partícula de reconocimiento de la señal en un paciente con polimiositis.

Idiopathic inflammatory myopathies are a heterogeneous group of potentially treatable myopathies. They are classified, on the basis of clinical and histopathological features, into four subtypes: dermatomyositis, polymyositis, necrotizing autoimmune myositis and inclusion-body myositis. Myositis-associated antibodies and myositis-specific autoantibodies are frequently found in patients with idiopathic inflammatory myopathies, and are useful in the diagnosis and classification. Anti-histidyl transfer RNA synthetase antibody is the most widely prevalent and is highly specific for polymyositis. Signal recognition particle antibody is also a specific autoantibody for polymyositis, but it is infrequent and rarely found in patients having other myositis-specific autoantibodies. We present a man with polymyositis who had both antibodies in serum, which is considered an extremely rare clinical situation. Here we analyze the clinical course and findings, and examine the effect of the coexistence and possible interaction on prognosis.

Association of the Shared Epitope, Smoking and the Interaction Between the Two With the Presence of Autoantibodies (Anti-CCP and RF) in Patients With Rheumatoid Arthritis in a Hospital in Seville, Spain. / Asociación del epítopo compartido, el tabaquismo y la interacción entre ambos con la presencia de autoanticuerpos (anti-PCC y FR) en pacientes con artritis reumatoide en un hospital de Sevilla, España.

OBJECTIVES: To evaluate the association of shared epitope, smoking and their interaction on the presence of autoantibodies (anti-cyclic citrullinated peptide [CCP] antibodies and rheumatoid factor) in patients with rheumatoid arthritis in our geographical area. METHODS: A descriptive and cross-sectional study was carried out in a cohort of 106 patients diagnosed with RA. Odds ratios (OR) for antibody development were calculated for shared epitope, tobacco exposure and smoking dose. Statistical analysis was performed with univariate and multivariate statistics using ordinal logistic regression. Odds ratios were calculated with 95% confidence interval (95% CI) and a value of P<.05 was considered significant. RESULTS: In univariate analysis, shared epitope (OR=2.68; 95% CI: 1.11-6.46), tobacco exposure (OR=2.79; 95% CI: 1.12-6.97) and heavy smoker (>20 packs/year) (OR=8.93; 95% CI: 1.95-40.82) were associated with the presence of anti-CCP antibodies. For rheumatoid factor, the association was only significant for tobacco exposure (OR=3.89; 95% CI: 1.06-14.28) and smoking dose (OR=8.33; 95% CI: 1.05-66.22). By ordinal logistic regression analysis, an association with high titers of anti-CCP (>200U/mL) was identified with South American mestizos, patients with homozygous shared epitope, positive FR and heavy smokers. CONCLUSIONS: Being a South American mestizo, having a shared epitope, rheumatoid factor positivity and a smoking dose>20 packs/year are independent risk factors for the development of rheumatoid arthritis with a high titer of anti-CCP (>200U/mL). In shared epitope-positive rheumatoid arthritis patients, the intensity of smoking is more strongly associated than tobacco exposure with an increased risk of positive anti-CCP.

Fasting Glycemia as Screening Tool to Rule-Out Gestational Diabetes in Low-Risk Population.

BACKGROUND: The use of a glucose challenge test as the universal screening for gestational diabetes is common in many countries. This test represents significant costs for laboratories and inconveniences for the patients, who have to wait for one hour and, very often, feel discomfort and nausea. In this work we propose the use of fasting glycemia, in a population with low prevalence of gestational diabetes as a pre-screening test that would avoid the oral glucose overload in those pregnant women with low risk of gestational diabetes. METHODS: The study was done with the fasting glucose levels of 6,573 pregnant women who underwent a two steps strategy to screen for gestational diabetes, a first step consisting of a 50 g glucose challenge test, followed when glycemia ≥ 140 mg/dL by a 100 g Oral Glucose Tolerance Test, based on recommendations made by National Diabetes Data Group. RESULTS: The ROC curve for fasting glucose was calculated, and we obtained an AUC = 0.633 (0.569 - 0.696). The sensitivity, specificity, and predictive values were established for different thresholds. CONCLUSIONS: We proposed that women with fasting glycemia ≤ 62 mg/dL, (S = 91.3%, NPV = 98.79% and LR- = 0.87) are in low risk of suffering gestational diabetes, which means that 10% of our population would not undergo the glucose challenge test.

Comparison of Citrate Buffer with Sodium Fluoride as Additives in Determining Glycemia.

BACKGROUND: The objectives of this study are to compare the effect of sodium fluoride and citrate on the stability of glucose in samples maintained at room temperature up to three hours, and to assess the clinical impact in the O'Sullivan test results after changing the additives in the collecting tubes. METHODS: The selected population was pregnant women between the 24th and 28th week of gestation, who were at the health center to undergo the O'Sullivan test as part of the screening program for GDM (gestacional diabetes mellitus). Two blood samples were extracted from each patient: one using a tube with citrate and sodium fluoride buffer (tubes Vacuette Glucomedics citrate, 2 mL, Ref 454347) (tube C) and another containing just sodium fluoride (BD Vacationer tubes FX fluoride, 2 mL, Ref 368920) (tube F). The statistical treatment of the data was performed using SPSS version 24 and Method validator. Finally, we assessed the real clinical impact of replacing tubes C for tubes F in the classification of pregnant women. To do so, we collected the results of O'Sullivan tests conducted in our hospital during a year, all of them done in tubes F, and we applied the mean difference calculated in T = 1 to estimate the number of pregnant women that should be reclassified. RESULTS: The average glycaemia in tubes C are significantly greater than average glycaemia in tubes F (p < 0.05) at all time points. The clinical impact assessment was done over the 6,526 O'Sullivan test results with a prevalence of positive tests of 21.35%. The prevalence using tubes C instead of tubes F estimated with mean differences previously calculated is 33.45%. CONCLUSIONS: The glucose concentrations in tubes F stored at room temperature up to 3 hours were significantly lower (p < 0.05) than those measured in tubes C stored under the same conditions. We observed that it is in the first minutes after extraction, while the samples are collected and aliquots done, that the glucose consumption occurs in tubes F, but not in tubes C. There is a need to change the preanalytical conditions to prevent any loss of glucose. This will enable more accurate diagnosis and management of diabetes mellitus.

Zenit RA evaluation, a solid-phase chemiluminescence immunoassay for detection of anti-cellular antibodies.

AIM: The objective was to compare Zenit RA chemiluminescent immunoassay (CLIA) from Menarini Diagnostics and ELISA from INOVA Diagnostics for the presence of specific anti-Ro/SS-A, anti-La/SS-B, anti-U1snRNP, anti-Sm, anti-Scl-70, anti-Jo-1 antibodies. Results/methodology: We studied 501 samples (178 connective autoimmune disease, 150 other autoimmune or inflammatory disease and 173 other disease or healthy). All samples were analyzed using CLIA and ELISA. The Kappa agreement was excellent for anti-SSA/Ro (0.864), good for anti-SSB/La (0.735), anti-Scl-70 (0.685) and ENA-screening (0.778), moderate for anti-RNP (0.563) and bad for anti-Sm (0.266) and anti-Jo-1 (0.243). Different combination of cut-off improved the specificity and agreement. CONCLUSION: Zenit RA CLIA for detecting autoantibodies, provides a simple, useful and accurate tool.

Association between serum dickkopf-1 levels and disease duration in axial spondyloarthritis.

BACKGROUND: Axial spondyloarthritis (axSpA) is characterized by new bone formation. The complex systems underlying this process involve Wnt-signaling pathway. It has been observed that serum levels of dickkopf-1 (DKK-1), an important inhibitor of Wnt-signaling, are decreased in patients with axSpA. However, these data are from studies including only patients with long-standing disease. The aim of this study is to investigate if symptom duration influences on serum DKK-1 levels in patients with axSpA. MATERIAL AND METHODS: A cross-sectional study including consecutive patients with axSpA (ASAS criteria) naïve for anti-TNF therapy. Collected data included demographic and disease characteristics, time since first symptom onset, assessment of disease activity and function, and determination of DKK-1 serum levels. Patients were classified as early axSpA (symptom duration ≤5 years) and established axSpA (>5 years). Linear regression models were employed to investigate the variables related to DKK-1 serum levels. RESULTS: In total, 90 patients were included. Sixty-eight patients had early axSpA and 22 had established disease. Serum levels of DKK-1 were significantly higher in patients with early axSpA compared with established axSpA (22.1±12.6 vs 16.4±10.7pM; p=0.04). Among all tested variables, only symptom duration was significantly and inversely correlated with DKK-1 serum levels (beta: -0.041; p=0.01). CONCLUSION: Serum DKK-1 levels in axSpA depend on disease duration. As disease duration increases, DKK-1 serum levels decrease. Based on this, an intensive treatment at early stages of the disease could have a better outcome on inhibiting/slowing radiographic progression in patients with axSpA.

[Increased lipoprotein(a) in a paediatric patient associated with nephrotic syndrome]. / Incremento de lipoproteína(a) en paciente pediátrico asociado a síndrome nefrótico.

A common complication in paediatric patients with nephrotic syndrome (NS) is hyperlipidaemia. About 20% of children do not respond to treatment with corticosteroids, presenting with a cortico-resistant NS (CRNS), which can progress to kidney failure. It has been observed that paediatric patients with CRNS have an elevated low density lipoprotein cholesterol (LDL-c), very low density lipoprotein cholesterol (VLDL-c), and triglycerides levels, as well as elevated Lipoprotein-a [Lp (a)] levels. The case is presented of a 5 year old boy, diagnosed with CRNS, presenting with dyslipidaemia with increased LDL-c, Apo-B100, and Lp(a) levels. After the poor prognosis of the renal function, immunosuppressant treatment was started with tacrolimus and atorvastatin to control dyslipidaemia. Although tacrolimus causes an elevation of total cholesterol and LDL-c, the significant alterations of the children lipid profile suggest the existence of a high cardiovascular risk. In these cases, it would be interesting to have reference values in children in our health area.

Evaluation of Bio-Rad D-100 HbA1c analyzer against Tosoh G8 and Menarini HA-8180V.

OBJECTIVES: To evaluate the Bio-Rad D-100®, an HPLC analyzer for glycated hemoglobin (HbA1c) determination, and to compare its performance with the Menarini HA-8180V® and Sysmex G8®. METHODS: Method comparison was performed according to Clinical and Laboratory Standards Institute (CLSI) EP9-A2 guidelines. We selected 100 samples from the routine laboratory workload and analyzed them in duplicate with the three analyzers. The imprecision study was performed according to CLSI EP5-A2 guidelines for both inter-assay and intra-assay variability. Bias was assessed with external quality control material. To establish linearity, CLSI EP6-A protocol was followed. RESULTS: Method comparison (95% confidence intervals in parentheses): D-100 vs G8: Passing-Bablok regression; y=0.973(0.963-0.983)×-0.07(-0.07-0.069); r=0.9989. Bland-Altman mean difference: -0.229%HbA1c (-0.256: -0.202); Relative bias plot: D-100/G8 vs D100-G8 mean ratio=0.971(0.967-0.975). D-100 vs HA-8180V: Passing-Bablok regression; y=0.944(0.932-0.958)×-0.078(0.024-0.173); r=0.9989. Bland-Altman mean difference: -0.363%HbA1c (-0.401: -0.325); Relative bias plot D-100/HA-8180V vs D100-HA-8180V mean ratio=0.955(0.952-0.958). Inter-assay coefficient of variation (CV): 0.81%. Intra-assay CV: 1.04% (low level), and 0.78% (high level). Bias against target value=2.332%. Linearity: r2=0.998 in the concentration range 4.4-13.9%HbA1c. Carry-over: 0.0024%. CONCLUSIONS: The Bio-Rad D-100 shows good correlation with G8 and HA-8180V. There is a small proportional systematic difference (2.7% and 5.6%, respectively) in both comparisons. Inter and intra-assay CVs are both lower than the lowest CV obtained in studies performed with D-100 and other instruments.

Evaluation of a HbA1c point-of-care analyzer.

OBJECTIVES: A better glycemic monitoring of diabetic patients and avoiding complications of poorly controlled diabetes could be possible with point-of-care testing technology (POCT) for HbA1c determination. B-Analyst® was studied to check whether it complied with the quality requirements for this purpose. DESIGN AND METHODS: We evaluated the B-Analyst® (Menarini Diagnostics), which is based in the principle of latex agglutination immunoturbidimetry, to assess the validity of the technique of HbA1c. We carried out the method comparison with the HA-8180® (Menarini Diagnostics) as a reference method [High Performance Liquid Chromatography (HPLC)]. We assessed the analytical quality of the B-Analyst® studying the accuracy: inter-assay variability and intra-assay study. Furthermore, possible interferences by hemoglobinopathies were studied. RESULTS: Regression analysis of the data for the method comparison between HA-8180® and B-Analyst® showed a slope of 1.0085 and an intercept of 0.1208. The Pearson's correlation coefficient was 0.9958 (p<0.0001). Bias study showed a mean difference from B-Analyst® with respect to HA-8180® of 0.1872 with a 95% confidence interval. The standard error of the estimate (Syx) was 0.2091. The concordance correlation coefficient to assess accuracy was 0.9922 (0.9891-0.9945). The CV for the inter-assay study was 1.4%. For the intra-assay study we analyzed 3 samples with different HbA1c % whose CV were 1.03% [4.7% HbA1c (28 mmol/mol)], 0.46% [6.4% HbA1c (46 mmol/mol)] and 0.78% [8.1% HbA1c (65 mmol/mol)]. CONCLUSION: The B-Analyst® evaluated not only showed good correlation with HA-8180®, but also it presented a great accuracy both in the inter-assay and in the intra-assay studies. The B-Analyst® complies with quality specifications required for monitoring of diabetic patients.

Análisis de anticuerpos antifosfolipídicos y cistatina C en pacientes con esclerosis múltiple / Analysis of antiphospholipid antibodies and cystatin C in multiple sclerosis patients / Teste de anticorpos antifosfolípídes e cistatina C em pacientes com esclerose múltipla

La cistatina C es considerada el inhibidor fisiológico más importante de las proteasas de cisteína endógenas. Se cree que el papel de la cistatina C es el de modular la actividad de las proteasas secretadas o liberadas de células dañadas o en proceso de necrosis, siendo por tanto las cistatinas fundamentales para los procesos de regulación y prevención del potencial daño proteolítico local. Los anticuerpos antifosfolípidos se usan para esclarecer el diagnóstico de esclerosis múltiple (EM) ya que existen patologías que pueden cursar con sintomatología o hallazgos paraclínicos semejantes. El objetivo de este trabajo fue analizar la concentración de cistatina C y la presencia o ausencia de anticuerpos antifosfolipídicos en pacientes diagnosticados de esclerosis múltiple remitente recurrente (EMRR) como marcadores de desmielinización. Este trabajo se llevó a cabo conjuntamente por el laboratorio de Riesgo Vascular, el laboratorio de Autoinmunidad y la Unidad de Esclerosis Múltiple del Hospital Universitario Virgen Macarena de Sevilla, España, con una duración de un año. Se seleccionaron dos tipos de poblaciones: grupo 1, n=30 pacientes con EMRR y un segundo grupo, denominado grupo control, n=30. Se determinó cistatina C y anticuerpos antifosfolípidos IgG e IgM, anticuerpos anticardiolipina IgG e IgM y anticuerpos f>2 glicoproteína IgG e IgM. Los pacientes diagnosticados de EMRR presentan títulos negativos de anticuerpos antifosfolípidos IgG e IgM, anticardiolipina IgG e IgM y f>2 glicoproteína IgG e IgM. La concentración de cistatina C es menor en el grupo de pacientes diagnosticados de EM, lo que podría producir un déficit en la modulación de las proteasas de cisteína endógenas. Dicha desmielini-zación agudizaría el progreso de la EM.

Cystatin C is considered the most important physiological inhibitor of endogenous cysteine proteases; the role of cystatin C is believed to be to modulate the activity of proteases secreted or released from damaged cells or in the process of necrosis, therefore cystatins being fundamental regulatory processes and a potential prevention of local proteolytic damage. Antiphospholipid antibodies are used to clarify the diagnosis of diseases like multiple sclerosis (MS) and other pathologies could present similai symptoms or paraclinical findings. The objective of the present work is to analyze the concentration of cystatin C and the presence or absence of antiphospholipid antibodies in patients diagnosed with relapsing remitting multiple sclerosis (RRMS) as markers of demyelization. This work was carried out jointly by the Vascular Risk Laboratory, the Laboratory of Autoimmunity and Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena in Seville in one year. Two types of people were selected: Group 1 (n = 30) RRMS group and a control group, n = 30. Cystatin C and antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM were determined. Patients showed negative titers of antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM. Cystatin C concentration is lower in the group of patients diagnosed with MS, which could give rise to a decrease in the modulation of endogenous cysteine proteases. This would exacerbate the progress of demyelization in MS.

A cistatina C é considerada o inibidor fisiológico das proteases de cisteína endógenas mais importante. Acredita-se que o papel da cistatina C é o de modular a atividade de proteases secretadas ou liberadas a partir de células danificadas ou em processo de necrose, sendo por isso as cistatinas fundamentais para os processos de regulagao e prevengao do potencial dano proteolítico local. Anticorpos antifosfolípides sao usados para esclarecer o diagnóstico de EM, visto que existem patologias que podem apresentar sintomas ou achados paraclínicos semelhantes. O objetivo deste trabalho foi o de analisar a concentra-gao de cistatina C e a presenga ou ausencia de anticorpos antifosfolípides em pacientes diagnosticados com esclerose múltipla recidivante - remitente (EMRR) como marcadores de desmielinizagao. Este trabalho foi realizado em conjunto pelo laboratório de Risco Vascular, o laboratório de Autoimunidade e a Unidade de Esclerose Múltipla do Hospital Universitario Virgen Macarena, de Sevilha, Espanha, com uma duragao de um ano. Foram selecionados dois tipos de populagdes-. Grupo 1 (n = 30) pacientes com EMRR e um segundo grupo, chamado de grupo controle, n = 30. Determinou-se cistatina C e anticorpos antifosfolípides IgG e IgM, anticorpos anticardiolipina IgG e IgM, e anticorpos $2 glicoproteína IgG e IgM. Pacientes diagnosticados com EMRR apresentam títulos negativos de anticorpos antifosfolípides IgG e IgM, anticardiolipina IgG e IgM e $2 glicoproteína IgG e IgM. A concentragao de cistatina C é menor no grupo de pacientes diagnosticados com EM, o que poderia produzir um déficit na modulagao das proteases de cisteína endógenas. Tal desmielinizagao agravaría o progresso da EM.

Interaction between oxidative stress and smoking is associated with an increased risk of rheumatoid arthritis: a case-control study.

OBJECTIVE: To investigate the relationship between oxidative stress and smoking and development of RA. METHODS: A case-control study was conducted in treatment-naïve early-onset RA patients and healthy controls, matched by age, gender and current smoking habit. Plasma lipid hydroperoxides (LOOH), carbonyl protein (CP) and malonyldialdehyde (MDA) levels were measured to estimate oxidative stress. Smoking exposure was quantified in pack-years. The presence of an interaction between oxidative stress and smoking exposure was investigated using three measures of additive interaction: relative excess risk due to the interaction (RERI), attributable proportion due to the interaction (AP) and the synergy index (S). RESULTS: A total of 65 RA patients and 65 healthy controls were included. Statistically significant differences were observed in RA-related variables, age, BMI and smoking dose between cases and controls. Plasma LOOH and CP levels were associated with RA risk, which was more prominent for LOOH levels >27.9 µM [odds ratio (OR) 18.8] and CP levels >64.3 µM (OR 24.9). A reverse association was observed between MDA levels and RA risk, OR 6.4 for MDA levels <8.5 µM. Having >20 pack-years increased risk for RA with an OR of 19.7. The interaction between smoking and oxidative stress increased RA risk significantly, and RERI between LOOH, CP or MDA and smoke exposure were 8.2, 5.0 and 51.5, respectively. CONCLUSION: These data suggest that the interaction between oxidative stress and smoking increases RA risk.

[Nutrition iodine status in pregnant women in the sanitary district Sierra de Huelva-Andévalo, South of Spain]. / Deficiencia nutricional de yodo en gestantes pertenecientes al distrito sanitario Sierra de Huelva-Andévalo, sur de España.

BACKGROUND: Iodine is an essential trace element implicated in synthesis of thyroid hormones. Iodine requirements vary throughout life. This iodine requirement is increased during pregnancy and breastfeeding. In a previous study carried out by our group in 2008, we detected an iodine-deficient area in the province of Huelva, specially in district Sierra de Huelva-Andévalo by means of neonatal TSH determinations. OBJECTIVE: To reinforce the iodine supplementation campaign and its impact on their newborns in order to assess nutrition iodine status in pregnant women using questionnaire and ioduria determination. MATERIAL AND METHODS: This study has been jointly carried out by Congenital Hypothyroidism Unit of the Clinical Biochemistry Department of the Virgen Macarena University Hospital (Seville) and the Gynecology and Clinical Analysis Unit of the Río Tinto Hospital (Huelva) during two years. We studied 313 pregnant women. All of them filled out a personal questionnaire to know the iodine nutritional status in their area. Ioduria was determinated by high-resolution liquid chromatography. Data from pregnant women and results of the studied variables were analyzed with SPSS v13.0. CONCLUSIONS: Pregnant women from the sanitary district Sierra de Huelva-Andévalo present a median for ioduria which corresponds to an insufficient iodine intake according to the WHO classification. The questionnaires suggest that this iodine deficiency is consequence of an insufficient iodine intake and a low adherence to the treatment.