ABSTRACT
BACKGROUND: Hyaluronic acid (HA) is present in many tissues; its presence in serum may be related to certain inflammatory conditions, tissue damage, sepsis, liver malfunction and some malignancies. In the present work, our goal was to investigate the significance of hyaluronic acid effect on erythrocyte flow properties. Therefore we performed in vitro experiments incubating red blood cells (RBCs) with several HA concentrations. Afterwards, in order to corroborate the pathophysiological significance of the results obtained, we replicated the in vitro experiment with ex vivo RBCs from diagnosed rheumatoid arthritis (RA) patients, a serum HA-increasing pathology. METHODS: Erythrocyte deformability (by filtration through nucleopore membranes) and erythrocyte aggregability (EA) were tested on blood from healthy donors additioned with purified HA. EA was measured by transmitted light and analyzed with a mathematical model yielding two parameters, the aggregation rate and the size of the aggregates. Conformational changes of cytoskeleton proteins were estimated by electron paramagnetic resonance spectroscopy (EPR). RESULTS: In vitro, erythrocytes treated with HA showed increased rigidity index (RI) and reduced aggregability, situation strongly related to the rigidization of the membrane cytoskeleton triggered by HA, as shown by EPR results. Also, a significant correlation (r: 0.77, p < 0.00001) was found between RI and serum HA in RA patients. CONCLUSIONS: Our results lead us to postulate the hypothesis that HA interacts with the erythrocyte surface leading to modifications in erythrocyte rheological and flow properties, both ex vivo and in vitro.
Subject(s)
Erythrocytes/metabolism , Hyaluronic Acid/pharmacology , Viscosupplements/pharmacology , Arthritis, Rheumatoid/blood , Blood Viscosity , Cytoskeletal Proteins/metabolism , Electron Spin Resonance Spectroscopy , Erythrocyte Deformability , Erythrocyte Membrane/metabolism , Erythrocytes/cytology , Female , Humans , Middle AgedABSTRACT
UNLABELLED: Increase in erythrocyte aggregation (EA) is pathognomonic for rheumatoid arthritis (RA), and its estimation through erythrocyte sedimentation rate (ESR) is part of DAS 28-4 activity diagnosis, with low correlation with EA and that does not discriminate the contribution of cell factors that increase aggregation. OBJECTIVE: To analyse cell and plasma factors that might be involved in EA increase, to understand how RA affects blood components, thus modifying blood fluid behavior. METHODOLOGY: One hundred women presenting active RA were compared with age-matched controls (C). EA was measured by transmitted light, obtaining two parameters: 2k2n0, characterizing the aggregation process kinetics and s0/n0, estimating aggregates size. Cell factors assays: erythrocyte deformability, by filtration through nucleopore membranes, cell shape, by microscopy, and membrane fluidity by EPR. Plasma: total proteins and CRP, albumin, fibrinogen (Fb), by gravimetry, and IgG and IgM by single radial immuno-diffusion. RESULTS: AR and C (x+/-SE). 2k2n0: 31.83+/-2.84, 23.75+/-1.91; s0/n0: 0.92+/-0.05, 0.87+/-0.04. Rigidity index (RI): 14.79+/-4.71, 6.92+/-1.31. Morphological index: 0.28+/-0.03, 0.30+/-0.05, n.s. Fb (mg/dl): 382+/-80, 299+/-70. IgG (mg/dl): 1580+/-219, 1296+/-158; IgM (mg/dl) 233+/-28, 183+/-23; albumin (g/dl) 3.84+/-0.44, 3.77+/-0.51 n.s. p<0.05 accepted. Correlations: 2k2n0 vs. Fb r=0.66; s0/n0 vs. Fb r=0.51; 2k2n0 vs. Igs r=0.65; s0/n0 vs. Igs r=0.56. 2k2n0 vs. RI r=-0.59; s0/n0 vs. RI=-0.52, p<0.05. CONCLUSIONS: Plasma factors, Igs and Fb increased aggregation, since RI is altered, this reduces the process efficiency regarding aggregation. Patients with active RA present an increased EA, with values modifications associated with the activity index DAS 28-4, thus becoming an RA activity indicator.
Subject(s)
Arthritis, Rheumatoid/blood , Erythrocyte Aggregation , Adult , Aged , Biomarkers/blood , Case-Control Studies , Erythrocyte Deformability , Female , Fibrinogen/analysis , Humans , Immunoglobulins/blood , Middle Aged , Rheumatoid Factor/blood , Severity of Illness IndexABSTRACT
Previous studies have demonstrated that in admixed populations, West African ancestry is associated with an increased prevalence of systemic lupus erythematosus (SLE). In the current study, the effect of Amerindian ancestry in SLE was examined in an admixed population in Argentina. The Argentine population is predominantly European with approximately 20% Amerindian admixture, and a very small (<2%) contribution from West Africa. The results indicate that Amerindian admixture in this population is associated with a substantial increase in SLE susceptibility risk (Odds Ratio=7.94, P=0.00006). This difference was not due to known demographic factors, including site of collection, age and gender. In addition, there were trends towards significance for Amerindian ancestry influencing renal disease, age of onset and anti-SSA antibodies. These studies suggest that populations with Amerindian admixture, like those with West African admixture, should be considered in future studies to identify additional allelic variants that predispose to SLE.
Subject(s)
Genetic Predisposition to Disease , Indians, South American/genetics , Lupus Erythematosus, Systemic/genetics , Algorithms , Argentina/epidemiology , Bayes Theorem , Case-Control Studies , Computational Biology/methods , Genetics, Population , Genotype , Geography , Haplotypes , Humans , Logistic Models , Odds Ratio , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
PDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.
Subject(s)
Antigens, CD/genetics , Antigens, CD/metabolism , Apoptosis Regulatory Proteins/metabolism , Genetic Predisposition to Disease , Intercellular Signaling Peptides and Proteins/genetics , Lupus Erythematosus, Systemic/genetics , Polymorphism, Single Nucleotide , B7-H1 Antigen , Female , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Ligands , Linkage Disequilibrium , Male , Programmed Cell Death 1 Ligand 2 Protein , Programmed Cell Death 1 ReceptorABSTRACT
OBJECTIVE: To investigate if blood hyperviscosity in RA patients is due to a reduced erythrocyte deformability and, therefore, turning it into a reliable activity indicator, as well as a therapy follow-up marker for this pathology. METHODS: (1) The haemorheological profile consisting of erythrocyte deformability, blood and plasma viscosity, and erythrocyte membrane fluidity was determined in 24 AR patients and 17 healthy controls. (2) A 4 year follow-up was carried on in 16 patients monitoring blood viscosity, erythrocyte deformability and biochemical variables in relation to clinical assessment of disease activity (Disease Activity Score "DAS 28-4"). RESULTS: Erythrocyte deformability and membrane fluidity were impaired in RA patients compared to controls (p<0.001). Blood viscosity was significantly increased and correlated with the cell rigidity index (r=0.85, p<0.0000) in RA patients. The follow-up showed a good correlation between haemorheological parameters and DAS 28-4 during disease evolution. CONCLUSION: our results support the hypothesis that in RA, blood hyperviscosity is determined by deformability loss, which in turn is due to a membrane rigidization. This could evidenced that a widespread cell membrane damage is expressed through an impaired erythrocyte deformability, turning haemorheological parameters into reliable tools to study disease evolution. The follow-up study enabled us to confirm that erythrocyte deformability is an efficient indicator of rheumatoid arthritis activity.
Subject(s)
Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Blood Viscosity , Adult , Case-Control Studies , Erythrocyte Deformability , Erythrocyte Membrane/metabolism , Erythrocyte Membrane/physiology , Female , Follow-Up Studies , Hematologic Tests , Humans , Membrane Fluidity , Middle AgedABSTRACT
Presentamos el caso de una niña de 1 año de edad, previamente sana, que desarrollo isquemia distal en 3, 4 y 5 dedos de la mano derecha y 3 dedo de la mano izquierda. Una vez realizada su evaluacion clinica y examenes complementarios, se diagnostico deficit de proteina C. Fue tratada, con resolucion completa de las lesiones. Discutimos los diagnosticos diferenciales, haciendo hincapie en la importancia de incluir enfermedades que pueden simular una vasculitis
Subject(s)
Humans , Infant , Fingers , Ischemia , Protein C Deficiency , ThrombophiliaABSTRACT
Presentamos el caso de una niña de 1 año de edad, previamente sana, que desarrollo isquemia distal en 3, 4 y 5 dedos de la mano derecha y 3 dedo de la mano izquierda. Una vez realizada su evaluacion clinica y examenes complementarios, se diagnostico deficit de proteina C. Fue tratada, con resolucion completa de las lesiones. Discutimos los diagnosticos diferenciales, haciendo hincapie en la importancia de incluir enfermedades que pueden simular una vasculitis (AU)
Subject(s)
Humans , Infant , Protein C Deficiency , Ischemia , Fingers , Thrombophilia/diagnosis , Thrombophilia/etiologyABSTRACT
Se estudian 32 pacientes y un grupo control de 10 personas con un protocolo que consta de : Cínica, inmunología y capilaroscopía. Esta última es una técnica de visualización in vivo de los capilares del lecho ungueal a traveés de una lupa estereos-cópica. Se analiza edad de aparición, correlación de los tres items del protocolo y enfermedad de base en Raynaud secundario. Los pacientes se dividieron en: Raynaud primario (7), Raynaud secundario (19) y Raynaud indeterminado (4). La sensibilidad del presente estudio para el diagnóstico diferencial fue del 81,3 por ciento. Además se analiza la alteración de la morfologá capilar y la injuria capilar (presencia de hemorragias) a nivel capilaroscópico
Subject(s)
Humans , Female , Adult , Capillaries , Diagnosis, Differential , Raynaud Disease/diagnosis , Raynaud Disease/immunologyABSTRACT
Se estudian 32 pacientes y un grupo control de 10 personas con un protocolo que consta de : Cínica, inmunología y capilaroscopía. Esta última es una técnica de visualización in vivo de los capilares del lecho ungueal a traveés de una lupa estereos-cópica. Se analiza edad de aparición, correlación de los tres items del protocolo y enfermedad de base en Raynaud secundario. Los pacientes se dividieron en: Raynaud primario (7), Raynaud secundario (19) y Raynaud indeterminado (4). La sensibilidad del presente estudio para el diagnóstico diferencial fue del 81,3 por ciento. Además se analiza la alteración de la morfologá capilar y la injuria capilar (presencia de hemorragias) a nivel capilaroscópico(AU)
