Insulin resistance metabolomic profile in non-diabetic women with systemic lupus erythematosus.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have a higher prevalence of insulin resistance (IR) and metabolic syndrome (MetS) than controls. OBJECTIVE: To evaluate IR in non-diabetic women with SLE by means of biomarkers using high-throughput metabolomic techniques. METHOD: Cross-sectional study in patients with SLE. A metabolomic approach was employed using ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry. MetS was evaluated according to NCEP-ATP III criteria. RESULTS: Seventy patients with SLE were included, out of whom 45 (64.2%) and 27 (38.5%) had IR and MetS, respectively. Patients with IR had a higher body mass index and hypertension more often than those without IR. Chronic damage and disease activity were not related to IR. A Quantose-IR score ≥ 63 was more common in patients with MetS (81.5 vs. 53.5%; p = 0.02). Quantose-IR score was also correlated with the number of criteria for MetS (r: 0.35; p = 0.003). CONCLUSIONS: In non-diabetic women with SLE, the prevalence of IR based on Quantose-IR score was 64.2%.

INTRODUCCIÓN: En lupus eritematoso sistémico (LES) es más frecuente la prevalencia de resistencia a la insulina (RI) y síndrome metabólico (SMet) que en controles. OBJETIVO: Evaluar la RI en mujeres no diabéticas con LES mediante biomarcadores usando técnicas metabolómicas de alta resolución. MÉTODO: Estudio transversal en pacientes con LES. Se empleó un abordaje metabolómico usando cromatografía de líquidos de ultra-alta resolución con espectrometría de masa de alta resolución. El SMet fue evaluado de acuerdo con los criterios NCEP-ATP III. RESULTADOS: Se incluyeron 70 pacientes con LES. Tuvieron RI y SMet 45 (64.2%) y 27 (38.5%), respectivamente. Pacientes con RI tenían un mayor índice de masa corporal e hipertensión con mayor frecuencia que aquellas sin RI. El daño crónico y la actividad de la enfermedad no se relacionaron con RI. Un puntaje de Quantose RI ≥ 63 fue más elevado en pacientes con SMet (81.5 vs 53.5%; p = 0.02). El puntaje Quantose RI también se correlacionó con el número de criterios para SMet (r: 0.35; p = 0.003). CONCLUSIONES: En mujeres con LES no diabéticas, la prevalencia de RI basada en el puntaje de Quantose RI fue del 64.2%.

Treatment of Persons with Multiple Myeloma in Underprivileged Circumstances: Real-World Data from a Single Institution.

BACKGROUND: The treatment of patients with multiple myeloma (MM) has evolved in recent years, and the disease-associated prognosis has improved substantially. This improvement has been driven largely by the approval of novel agents, many of which are expensive and not universally available. Less expensive but effective approaches would be of value globally. PATIENTS AND METHODS: All consecutive MM patients diagnosed in the Centro de Hematología y Medicina Interna de Puebla after 1993 were included in this study. Patients were given oral thalidomide (100 mg/day), oral dexamethasone (36-40 mg/week), and aspirin 100 mg/day. Bor-tezomib (1.75 mg s.c. every week) was administered to those who could afford it. After 4-6 weeks of treatment, patients were offered an outpatient-based hematopoietic cell transplant (HCT). After the recovery of granulocytes following HCT, patients continued indefinitely on thalidomide; those who failed to tolerate thalidomide were switched to lenalidomide (25 mg/day). RESULTS: The median overall survival (OS) for all patients has not been reached and is >157 months. Median follow-up of the patients lasted 14 months (range 1.3-157). The median OS of patients with and without HCT was similar. The response rate (complete remission or very good partial remission) was 72% for those given thalidomide plus dexamethasone versus 88% for those given bortezomib, thalidomide, and dexamethasone before HCT, but OS was not different. As post-HCT maintenance, 37 patients received thalidomide; 26 of those (70%) could be maintained indefinitely on thalidomide, whereas 11 were switched to lenalidomide after a median of 7 months; median OS of patients maintained on thalidomide or lenalidomide after HCT was not different. CONCLUSION: In this series, a regimen incorporating low-cost novel agents and outpatient HCT was associated with excellent long-term survival in the treatment of MM patients. This approach may be a model for MM treatment in underprivileged circumstances.

Determine safety of outpatient chemotherapy and autotransplants using refrigerated, non-frozen grafts in persons with multiple sclerosis.

BACKGROUND: Persons with multiple sclerosis are increasingly treated with intermediate- or high-dose chemotherapy and a hematopoietic cell autotransplant. This is often done in an inpatient setting using frozen blood cell grafts. OBJECTIVE: Determine if chemotherapy and a hematopoietic cell autotransplant can be safely done in an outpatient setting using refrigerated, non-frozen grafts. METHODS: We developed an autotransplant protocol actionable in an outpatient setting using a refrigerated, non-frozen blood graft collected after giving cyclophosphamide, 50 mg/kg/d × 2 days and filgrastim, 10 µg/kg/d. A second identical course was given 9 days later followed by infusion of blood cells stored at 4°C for 1-4 days. The co-primary outcomes were rates of granulocyte and platelet recovery and therapy-related mortality. RESULTS: We treated 426 consecutive subjects. Median age was 47 years (range, 21-68 years). A total of 145 (34%) were male. Median graft refrigeration time was 1 day (range, 1-4 days). Median interval to granulocytes >0.5 × 10E + 9/L was 8 days (range, 2-12) and to platelets >20 × 10E + 9/L, 8 days (range, 1-12). Only 15 subjects (4%) were hospitalized, predominately for iatrogenic pneumothorax (N = 5) and neutropenic fever (N = 4). There was only 1 early death from infection. CONCLUSION: Intermediate-dose chemotherapy and a hematopoietic cell autotransplant can be safely done in an outpatient setting using, refrigerated, non-frozen grafts.

[Reporte de la Primera Reunión Nacional de Consenso para la Inmunofenotipificación de Leucemias Agudas].

En 2005 se publicaron recomendaciones para la tipificación de hemopatías malignas en Latinoamérica. Se consideró necesario realizar una reunión nacional para actualizarlas. Se convocaron y reunieron 95 profesionales expertos en el tema para analizar y contrastar alternativas y llegar a un consenso. Se alcanzaron opiniones de consenso en lo relativo a indicaciones, tipos y manejo de muestras, anticuerpos, nomenclatura e informe de resultados para el diagnóstico y seguimiento de las leucemias agudas. Las recomendaciones se describen en este artículo y se hace hincapié en la necesidad de que los laboratorios nacionales se apeguen a ellas.

Recommendations for the typing of hematological malignancies in Latin America were published in 2005. Carrying out a national meeting to update them was deemed necessary. 95 professional experts on the subject were invited in order to analyze and contrast alternatives and reach a consensus. Consensus opinions were reached regarding indications, sample types and processing, antibodies, nomenclature and reporting of results for the diagnosis and monitoring of acute leukemias. This paper describes the recommendations and emphasizes on the need for national laboratories to adhere to them.

The Role of Circulating Regulatory T Cell Levels on Subclinical Atherosclerosis and Cardiovascular Risk Factors in Women with Systemic Lupus Erythematosus.

The increase in cardiovascular disease (CVD) in patients with systemic lupus erythematosus (SLE) is not fully explained by traditional CVD risk factors. Regulatory T cells (Treg cells) are considered atheroprotective. We investigated the relationship between the absolute number of different phenotypes of Treg cells and abnormal carotid intima-media thickness (IMT) in women with SLE. Sixty-six women with SLE with no history of CV disease were included. Carotid IMT was quantified by ultrasound. Abnormal carotid IMT was defined as ≥0.8 mm and two groups were compared according to this definition. Flow cytometry was used to analyze Foxp3 and Helios expression in peripheral blood CD4 T cells. A significantly higher level of absolute CD4+CD25+FoxP3high T cells was present in patients with abnormal carotid IMT compared with those without (1.795 ± 4.182 cells/µl vs. 0.274 ± 0.784 cells/µl; p = 0.003). However, no correlations were found between any Treg cell phenotypes and carotid IMT. Only the absolute number of CD4+CD45RA+FoxP3low T cells was significantly decreased in SLE patients with low HDL cholesterol compared with those with normal HDL cholesterol (0.609 ± 2.362 cells/µl vs. 1.802 ± 4.647 cells/µl; p = 0.009 and 15.358 ± 11.608 cells/µl vs. 28.274 ± 34.139; p = 0.012, respectively). In conclusion, in SLE women, diminished levels of Treg cells based on flow cytometry were not a good indicator of abnormal carotid IMT.

Vß T cell receptor (TCR) genes in circulating cells of patients with systemic lupus erythematosus and their healthy relatives / Genes del receptor variable beta de células T en células circulantes de pacientes con lupus eritematoso generalizado y sus familiares sanos.

Objective: We investigated the proportion of Vß T cell receptor (TCR) gene expression in peripheral CD3+ lymphocytes in familial and non-familial systemic lupus erythematosus (SLE) patients. Method: The Vß TCR repertoire was studied in 14 families in which several members had SLE. The Vß TCR usage in SLE patients (n = 27) was compared with that in healthy members of these multiplex families (n = 47), in 37 sporadic SLE patients who had no relatives with SLE, and in 15 healthy unrelated controls. Vß TCR repertoire expression was studied by multiparameter flow cytometry with the use of an array of 24 different Vß TCR gene family-specific monoclonal antibodies. Results: We found the same Vß TCR expression profile in the comparisons between sporadic SLE and familial SLE cases and healthy relatives, which included increased expression of Vß 5.2, Vß 11 and Vß 16, and lower expression of Vß 3, Vß 4, Vß 7.1 and Vß 17. Interestingly, solely Vß 17 was differentially expressed among sporadic and familial SLE. Also, increased expression of Vß 9 was the hallmark among familial SLE (casesand h ealthy relatives) in comparison to controls. Conclusion: These results highlight the notion that the final profile of the Vß TCR repertoire seen in familial and non-familial SLE seems to arise from the interaction of genetic, environmental, and immunoregulatory factors. Furthermore, it may contribute to the immunologic abnormalities affecting relatives of SLE patients.

Objetivo: Se investigó la proporción de la expresión génica del receptor variable beta de células T (Vß TCR) en linfocitos periféricos CD3+ en pacientes con lupus eritematoso generalizado (LEG) familiar y no familiar. Método: El repertorio de Vß TCR se estudió en 14 familias que presentaban más de un miembro con LEG. El uso de Vß TCR en pacientes con LEG (n = 27) se comparó con el de los miembros sanos de estas familias (n = 47), con 37 pacientes con LEG esporádico y con 15 controles sanos. La expresión del repertorio de Vß TCR se estudió por citometría de flujo multiparamétrica utilizando un arreglo de 24 diferentes anticuerpos monoclonales específicos de genes familiares para Vß TCR. Resultados: Se encontró el mismo perfil de expresión en las comparaciones entre los casos de LEG esporádico y familiar, así como en los consanguíneos sanos de las familias multicasos, que incluía una expresión incrementada de Vß 5.2, Vß 11 y Vß 16, y una menor expresión de Vß 3, Vß4, Vß 7.1 y Vß 7. De manera interesante, solo Vß 17 se expresó de modo diferente entre casos familiares y esporádicos de LEG. Igualmente, la expresión incrementada de Vß 9 fue el distintivo entre los casos de LEG familiar (casos y consanguíneos sanos) y los controles sanos. Conclusiones: Estos resultados refuerzan la noción de que el perfil final del repertorio Vß TCR observado en LEG familiar y no familiar parece surgir de la interacción de factores genéticos, ambientales e inmunorreguladores, además de que pueden explicar las alteraciones inmunitarias que se observan en los consanguíneos sanos de pacientes con LEG.

A Feasibility Study of the Full Outpatient Conduction of Hematopoietic Transplants in Persons with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells.

BACKGROUND: With the goal of achieving immune system reset, autologous hematopoietic stem cell transplantations have been performed in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Two hundred and eighty-six consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSCs), on an outpatient basis and conditioning with cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217. RESULTS: One hundred and ninety-four females and 92 males were included; the median age was 47. All procedures were started on an outpatient basis and only 8 persons needed to be admitted to the hospital during the procedure. In order to obtain at least 1 × 106/kg viable CD34 cells, 1-4 aphereses were performed (median 1). The total number of viable CD34+ cells infused ranged between 1 and 19.2 × 106/kg (median 4.6). Patients recovered above 0.5 × 109/L absolute granulocytes on median day 8 (range 0-12). Two individuals needed red blood cells but none needed platelet transfusions. There were no transplant-related deaths and the 128-month overall survival of the patients is 100%. In 82 persons followed up for 3 or more months, the Expanded Disability Status Scale diminished from a mean of 5.2-4.9, the best results being obtained in relapsing-remitting and primary progressive MS. CONCLUSIONS: It is possible to conduct autotransplants for patients with MS employing non-frozen PBSCs and outpatient conduction. Additional information is needed to assess the efficacy of these procedures in the treatment of patients with MS.

Serum Antibodies to Melanocytes in Patients With Vitiligo Are Predictors of Disease Progression.

The aim of this study was to investigate whether the amount of serum antibodies to melanocyte antigens could predict clinical activity or disease progression in patients with vitiligo. A solid-phase enzyme immunoassay was developed to semiquantitate serum antibodies to a human melanocyte extract and was used in 127 patients, 93 of whom showed clinical progression of the disease, while the remaining 34 were quiescent. Results showed different values for clinical sensitivity and specificity depending on the cutoff level for decision, but the overall performance of the test was adequate and supported statistical significance to predict clinical activity/progression or quietness of the disease process. The test might prove useful in deciding the indication and aggressiveness of immunosuppressive therapy in patients with vitiligo. Previous findings suggest that melanocyte-specific antibodies might play a pathogenetic role in the depletion of melanocytes, which characterizes this disorder, and that this depletion might be due to apoptosis following antibody internalization.

Mexican Biosimilar Filgrastim for Autologous Hematopoietic Stem Cell Mobilization and Transplantation.

BACKGROUND: Following the release of the initial presentation of filgrastim (granulocyte colony-stimulating factor), several biosimilars have been developed worldwide. OBJECTIVE: To study the efficacy of a Mexican biosimilar granulocyte colony-stimulating factor in a single transplant center. METHODS: In a group of 19 consecutive patients with multiple sclerosis given autografts, we employed granulocyte colony-stimulating factors to mobilize stem cells from the bone marrow to the peripheral blood, either the original granulocyte colony-stimulating factor (n = 10) or a Mexican granulocyte colony-stimulating factor biosimilar (n = 9). RESULTS: The efficacy of both agents was similar in mobilization capacity, white blood cell count rise, stem cell collection, and kinetics of auto-engraftment. CONCLUSION: We conclude that both granulocyte colony-stimulating factor agents were similar in their efficacy to mobilize stem cells and usefulness in autografts.

[Donor cell leukemia (DCL): A prospective study of its identification and treatment]. / Leucemia en células del donador (LCD): un estudio prospectivo de su identificación y tratamiento.

Donor-derived malignancies after allogeneic hematopoietic stem cell transplantation and after solid organ transplantation are considered as rare diseases. We have prospectively searched for donor cell leukemia in a 12-year period, in a single institution, in a group of 106 consecutive patients allografted because of leukemia. We have identified seven cases of donor cell leukemia; six were allografted because of relapsed acute lymphoblastic leukemia and one because of paroxysmal nocturnal hemoglobinuria/aplastic anemia. These figures suggest that the real incidence of donor cell leukemia has been underestimated. The six patients with lymphoblastic donor cell leukemia were treated prospectively with a pediatric-inspired combined chemotherapy schedule designed for de novo acute leukemia. A complete response was obtained in three out of six patients with lymphoblastic donor cell leukemia. It is possible to obtain favorable responses in donor cell leukemia patients employing combined chemotherapy. The long-term donor cell leukemia survivors remain as full chimeras and have not needed a second transplant.

Poor performance of the total kappa/lambda light chain quantification in the diagnosis and follow-up of patients with multiple myeloma.

BACKGROUND: The gold standard for paraproteinemia screening in plasma cell disorders has been serum protein electro- phoresis (SPE) with immunofixation electrophoresis (IFx); serum total and free light chain quantifications have also been used. OBJECTIVE: To define the role of SPE, IFx and serum total light chain (sLC) determinations in patients with multiple myeloma (MM), both at diagnosis and at maximum response during treatment follow-up. MATERIAL AND METHODS: These serological studies were performed in a group of 62 patients with MM at diagnosis, and in a subset of 29 patients at the point of maximum response to treatment. RESULTS: At diagnosis, we found an abnormal SPE in 58%, an abnormal IFx in 92% and an abnormal sLC in 45% of the 62 patients; 64% had simultaneously abnormal results in all three serological studies. IFx alone proved to be the most sensitive of all three assays, followed by SPE, which was redundant in most instances with sLC and IFx. At maximum response, the abnormal SPE normalized in 7 cases, the abnormal IFx in 7 cases and the abnormal sLC in 7 cases. There were 12 instances in which an abnormal IFx was found despite normal sLC, and one case in which a normal IFx was found in the presence of abnormal sLC. The association between IFx and sLC was highly significant (r = 0.9274611, p < 0.000001), despite instances where a positive result for IFx was associated to a normal sLC. CONCLUSION: All three serological methods should ideally be simultaneously performed in patients with MM both at diagnosis and throughout therapy. In this series, the total sLC assay was not more sensitive than IFx neither at diagnosis nor during follow-up.

Vitamin D in systemic lupus erythematosus with and without lupus nephritis.

INTRODUCCIÓN: Las concentraciones séricas subóptimas de vitamina D se presentan en múltiples enfermedades crónicas, como las enfermedades autoinmunitarias. Los objetivos del estudio fueron: 1) comparar las concentraciones séricas de 25-hidroxivitamina D (25OHD3) en pacientes con lupus eritematoso sistémico (LES) con y sin nefritis lúpica (NL), y 2) evaluar la asociación de las concentraciones séricas de 25OHD3 con la actividad de la enfermedad. MATERIAL Y MÉTODOS: Estudio comparativo, transversal, que incluyó 48 mujeres con LES, con y sin NL. Se excluyeron aquellas con enfermedad renal crónica en estadio IV, cáncer, hiperparatiroidismo, embarazo o lactancia. La actividad fue evaluada con el instrumento SLEDAI-2K. La concentración sérica de 25OHD3 se determinó mediante inmunoanálisis quimioluminiscente. RESULTADOS: La media de edad de las pacientes con y sin NL fue de 36.3 ± 8.6 años y 42.7 ± 7.6 años, respectivamente. Se observó una elevada prevalencia de valores subóptimos de 25OHD3 en todas las pacientes (93%). Las concentraciones séricas de 25OHD3 fueron diferentes entre pacientes con y sin NL: 21.5 ± 6.8 ng/ml frente a 19.2 ± 7.1 ng/ml (p = 0.362). No se encontró correlación entre la concentración sérica de 25OHD3 y la actividad de la enfermedad (r = -045, p = 0.761). CONCLUSIONES: En pacientes con LES, las concentraciones séricas de 25OHD3 fueran diferentes entre pacientes con y sin NL; sin embargo, esta diferencia no fue significativa. Además, no se encontró correlación entre las concentraciones séricas de 25OHD3 y la actividad de la enfermedad evaluada por SLEDAI-2K. BACKGROUND: Sub-optimal serum vitamin D levels occur in multiple chronic diseases such as autoimmune diseases. The objectives of this study were: 1) compare the serum concentration of 25-hidroxivitamin D (25OHD3) in patients with systemic lupus erythematosus (SLE) with and without lupus nephritis (LN), and 2) evaluate the association of serum concentration of 25OHD3 with the activity of the disease. MATERIAL AND METHODS: A comparative, cross-sectional study was conducted, including 48 women with SLE, with and without clinical diagnosis of LN, according to the score of renal activity evaluated by SLEDAI-2K. Patients with stage IV chronic kidney disease, cancer, hyperparathyroidism, pregnancy and lactation were excluded. The activity was evaluated by the SLEDAI-2K instrument. The serum concentration of 25OHD3 was assessed by chemiluminescent immunoassay. RESULTS: The mean age of patients with and without LN was 36.3 ± 8.6 and 42.7 ± 7.6 years, respectively. High prevalence of suboptimal 25OHD3 levels was observed (93%). 25OHD3 concentrations were different between patients with and without LN, 21.5 ± 6.8 ng/mL vs. 19.2 ± 7.1 ng/mL (p = 0.362). No correlation was found between serum 25OHD3 concentration (r = −045, p = 0.761). CONCLUSIONS: There were no differences found in serum concentrations of 25OHD3 in patients with or without NL. Moreover, no correlation was found between serum 25OHD3 levels and the activity of the disease evaluated by SLEDAI-2K.

Glomerular Filtration Rate in Patients with Multiple Sclerosis Undergoing Stem Cell Transplantation and Treated with Cyclophosphamide.

BACKGROUND: Glomerular filtration rate (GFR) is partially impaired in patients with multiple sclerosis (MS). When given chemotherapy before receiving hematopoietic stem-cell transplantation, GFR might be further deteriorated. OBJECTIVE: To measure the effect of cyclophosphamide on GFR in patients with MS who undergo chemotherapy. METHODS: We estimated GFR based on creatinine and cystatin C plasma concentrations in patients undergoing autologous hematopoietic stem-cell transplantation to treat their MS. RESULTS: Baseline GFR values were lower in the 28 patients with MS than in the 20 healthy individuals. Also, according to the Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) 2012 Creat-CysC equation criteria, 4 of 28 patients were classified as having chronic kidney disease (CKD) before receiving the chemotherapy drugs. After receiving 4 × 50 mg per kg body weight cyclophosphamide, abnormal GFR results were recorded in 12 of 28 patients. CONCLUSIONS: Renal function must be monitored in patients with MS undergoing autologous stem-cell transplantation. Also, chemotherapy should be constrained as much as possible to prevent further deterioration of renal function.

Systemic lupus erythematosus and hypertension.

Systemic lupus erythematosus (SLE) is associated with a high burden of cardiovascular disease (CVD), which is in part imputed to classical vascular risk factors such as hypertension. Hypertension is frequent among patients with SLE and studies show it is more prevalent in SLE patients than in people without SLE. Despite the high frequency of hypertension in SLE patients, the pathophysiological mechanisms underlying the development of hypertension remain poorly understood. 24-h ambulatory blood pressure monitoring has emerged as a valuable tool in determining blood pressure (BP) in SLE patients in whom hypertension has been associated with damage accrual, stroke and cognitive dysfunction. Although prevalent, current guidelines neglect the specific management of hypertension in SLE patients in their recommendations. This review discusses the mechanisms that may lead to hypertension and the literature evaluating hypertension screening and management in SLE patients.

25-Hydroxyvitamin D concentrations and risk of metabolic syndrome in systemic lupus erythematosus women.

OBJECTIVE: A protective function of vitamin D in metabolic syndrome (MetS) has been described. The objective of the present study was to examine the relationship between serum 25-hydroxyvitamin D (25(OH)D) concentrations and MetS in non-diabetic systemic lupus erythematosus (SLE) women. METHODS: Cross-sectional analyses of the relationship between concentrations of 25(OH)D, MetS, and its components were made in 160 non-diabetic SLE women. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. Serum 25(OH)D was measured by chemiluminescent immunoassay. Serum 25(OH)D concentrations were categorized into quartiles (<16.6, 16.6-21.1, 21.2-26.3, ≥26.4 ng/mL). RESULTS: A total of 79 (49.3%) SLE women had MetS. Without adjusting for body mass index (BMI) or smoking, the odds of having MetS decreased according to increasing quartiles of 25(OH)D concentrations (P for trend = .03). The odds ratio (OR) of having MetS was 0.4 (95% confidence interval: 0.2-0.9, P = .04) for the highest vs the lowest quartile of 25(OH)D concentrations when adjusted by age. The crude OR of having elevated hypertriglyceridemia decreased according to increasing quartiles of 25(OH)D concentrations (P for trend = .036). However, further adjustments for BMI and smoking removed the inverse association between 25(OH)D concentrations and MetS and its individual components. CONCLUSION: In non-diabetic SLE women with mild activity, 25(OH)D concentrations are not associated with MetS and its components.

Metabolomic profile of insulin resistance in patients with multiple sclerosis is associated to the severity of the disease.

BACKGROUND: Dysglycemia and adiposity have been related to disability in patients with multiple sclerosis. The objective of this work was to determine the prevalence and characteristics of insulin resistance in patients with multiple sclerosis using the metabolomics Quantose score. METHODS: A total of 64 patients were accrued in the study. A blood sample was drawn to estimate the Quantose score, which is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal. RESULTS: Insulin resistance was documented in 33 out of 64 patients and it was found in association with the degree of disability and the time from diagnosis. Patients with the secondary progressive form of the disease showed the highest prevalence. CONCLUSION: Insulin resistance is frequent in patients with multiple sclerosis and might contribute to metabolic complications and general disability. Early markers of dysglycemia should be sought for in these patients to avoid additional deterioration of their quality of life.

Simultaneous use of multiplex ligation-dependent probe amplification assay and flow cytometric DNA ploidy analysis in patients with acute leukemia.

BACKGROUND: The aim of this work was to simultaneously use multiplex ligation-dependent probe amplification (MLPA) assay and flow cytometric DNA ploidy analysis (FPA) to detect aneuploidy in patients with newly diagnosed acute leukemia. METHODS: MLPA assay and propidium iodide FPA were used to test samples from 53 consecutive patients with newly diagnosed acute leukemia referred to our laboratory for immunophenotyping. Results were compared by nonparametric statistics. RESULTS: The combined use of both methods significantly increased the rate of detection of aneuploidy as compared to that obtained by each method alone. The limitations of one method are somehow countervailed by the other and vice versa. CONCLUSIONS: MPLA and FPA yield different yet complementary information concerning aneuploidy in acute leukemia. The simultaneous use of both methods might be recommended in the clinical setting. © 2017 International Clinical Cytometry Society.

The role of complement regulatory proteins (CD55 and CD59) in the pathogenesis of autoimmune hemocytopenias.

Mammalian cells are provided with surface-bound complement regulatory proteins that protect them from uncontrolled complement-mediated lysis. Two of these regulators in humans, CD55 and CD59, are glycosylphosphatidylinositol-anchored, type I cell surface proteins, which inhibit formation of the C3 convertases and prevent the terminal polymerization of the membrane attack complex, respectively. Paroxysmal nocturnal hemoglobinuria is a genetic disorder due to the impaired conformation of the glycosylphosphatidylinositol-anchor, that results in the deficient expression of CD55 and CD50 which leads to excessive destruction of red cells and leukocytes. We have studied the expression of these two molecules in patients with autoimmune hemolytic anemia, autoimmune thrombocytopenia, and patients with systemic lupus erythematosus showing lymphopenia, and found that all three types of cytopenias are associated to deficient expression of CD55 and CD59 on the involved hematopoietic lineage. These are the first descriptions of acquired deficiencies of complement regulatory molecules in human disease, and it seems, from our results, that such deficiencies might play a pathogenic role in the mechanism of cell destruction. Although autoantibodies appeal as the best candidates to cause underexpression of CD55 and CD59, the search for an association to the presence and titers of most frequent self-reactive antibodies has proved non-existent.

Donor cell leukemia: a critical review.

Approximately 40 cases of DCL have been reported in the literature; cases have been reported after allografts from bone marrow, peripheral blood and cord blood. The study of these cases may provide new insights into the mechanisms of leukemogenesis. Some data suggest that the prevalence of this complication has been under-estimated. Most cases of DCL have occurred following transplantation for leukemia, but there have also been cases reported after transplantation for non-malignant conditions. Various mechanisms have been proposed to explain how DCL arise and are briefly discussed. Additional studies are needed to define with more detail both the true prevalence of this complication and its precise pathogenetic mechanism.