RESUMO
OBJECTIVE: To assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE). METHODS: Single-nucleotide polymorphisms (SNPs) within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation between ancestry and the presence of risk alleles was analyzed using linear regression. RESULTS: A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, ITGAM, and IRF5 were associated with lupus in a Hispanic Mestizo cohort enriched for European and Amerindian ancestry. In addition, 2 SNPs within the major histocompatibility complex region, previously shown to be associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression, we predicted an average increase of 2.34 risk alleles when comparing an SLE patient with 100% Amerindian ancestry versus an SLE patient with 0% Amerindian ancestry (P < 0.0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele. CONCLUSION: Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.
Assuntos
Indígena Americano ou Nativo do Alasca/etnologia , Indígena Americano ou Nativo do Alasca/genética , Frequência do Gene/genética , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/genética , Antígeno CD11b/genética , Estudos de Casos e Controles , Humanos , Fatores Reguladores de Interferon/genética , América Latina , Modelos Lineares , Ligante OX40/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Fator de Transcrição STAT4/genéticaRESUMO
OBJECTIVES: to detect the prevalence of hyperhcy in SLE patients with and without antiphospholipid syndrom; to compare the Hcy levels between those patients and healthy controls and to determine the correlation between hyperhcy and antiphospholipid antibodies. PATIENTS AND METHODS: we studied 44 SLE patients: 17 had antiphospholipid syndrom and 27 didn't have it, and we compared them to 24 healthy controls. All of them where checked clinically and with laboratory tests like anticardiolypin antibodies, lupus anticoagulant and Hcy. Hcy > 9 was considered abnormal. Patient who had hyperhcy were treated with folic acid+vitB6+vitB12 a month along. STATISTICAL ANALYSIS: cualytative variables: chi square or Fischer's; cuantitative variables: Student's T test or Mann-Whitney's test. RESULTS AND CONCLUSIONS: there were 35 trombotic manifestations in 44 patients. Hyperhcy was present in 27 SLE patients (61,4%), 12 of them had antiphospholipid syndrom. Hcy concentrations patients vs.controls was statisticaly different (p= 0,002). There was also stastisticaly different the hcy concentration from SLE patients with SAF vs controls (p=0,003) and without SAF vs controls (p= 0,015). From 33 SLE patients, 20 (33%) were aCL(+). 15(75%) of them had hiperhcy.
Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/complicações , Homocisteína/sangue , Hiper-Homocisteinemia/complicações , Lúpus Eritematoso Sistêmico/complicações , Trombose/etiologia , Adulto , Idoso , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/epidemiologia , Argentina/epidemiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Hiper-Homocisteinemia/sangue , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores de RiscoRESUMO
OBJECTIVES: to detect the prevalence of hyperhcy in SLE patients with and without antiphospholipid syndrom; to compare the Hcy levels between those patients and healthy controls and to determine the correlation between hyperhcy and antiphospholipid antibodies. PATIENTS AND METHODS: we studied 44 SLE patients: 17 had antiphospholipid syndrom and 27 didn't have it, and we compared them to 24 healthy controls. All of them where checked clinically and with laboratory tests like anticardiolypin antibodies, lupus anticoagulant and Hcy. Hcy > 9 was considered abnormal. Patient who had hyperhcy were treated with folic acid+vitB6+vitB12 a month along. STATISTICAL ANALYSIS: cualytative variables: chi square or Fischer's; cuantitative variables: Student's T test or Mann-Whitney's test. RESULTS AND CONCLUSIONS: there were 35 trombotic manifestations in 44 patients. Hyperhcy was present in 27 SLE patients (61,4%), 12 of them had antiphospholipid syndrom. Hcy concentrations patients vs.controls was statisticaly different (p=0,002). There was also stastisticaly different the hcy concentration from SLE patients with SAF vs controls (p=0,003) and without SAF vs controls (p= 0,015). From 33 SLE patients, 20 (33%) were aCL(+). 15(75%) of them had hiperhcy.
Assuntos
Síndrome Antifosfolipídica/fisiopatologia , Hiper-Homocisteinemia/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Trombose/etiologia , Adulto , Idoso , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Argentina , Feminino , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/sangue , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trombose/sangue , Trombose Venosa/sangueRESUMO
INTRODUCTION: There are no medical publications with economic analysis of rheumatoid arthritis patients (RA) from Argentina are lacking. The objective of the present study is to determine the direct cost and its breakdown in patients with RA. MATERIAL AND METHODS: Fifty-two patients who met the American College of Rheumatology RA criteria were included. Direct cost was calculated over a follow-up period of 6 months during year 2001. Variables were analyzed with Student's T test, Mann-Whitney U Test, c' or ANOVA as corresponded. P values < 0.05 were considered significant. RESULTS: The mean monthly home income was $426.6 SD 272. The mean half-yearly direct costs was $677.5 SD 376.2. The components of the direct cost were identified and the mean for medication cost was $606.7 (89%), for lab tests was $45.5 (7%), for medical attention $12.5 (2%) and other costs $2.4. No differences in total cost or in medication cost were found when compared considering age, evolution time of RA or HAQ scores. CONCLUSION: Half-yearly direct cost in RA is excessively high considering the monthly mean income of the patients being analyzed. The cost of medication was the principal component of the direct cost.
Assuntos
Artrite Reumatoide/economia , Custos Hospitalares/estatística & dados numéricos , Hospitais Universitários , Análise de Variância , Argentina , Artrite Reumatoide/terapia , Feminino , Seguimentos , Humanos , Masculino , Estatísticas não Paramétricas , Fatores de TempoRESUMO
Objetivos: Analizar las características sociodemográficas y clínicas de los pacientes con Lupus Eritematoso Sistémico (LES) del Servicio de Reumatología de un Hospital Universitario de Córdoba. Pacientes y métodos: Estudio retrospectivo, descriptivo y analítico de 303 pacientes adultos con LES asistidos entre 1987-2017, que cumplían con los criterios ACR1982. Se registraron datos sociodemográficos, clínicos, de laboratorio, internaciones, óbitos y los tratamientos. Los datos fueron analizados con Excel, Infostat y SPSS 11.5 para Windows. Resultados: El 92% eran mujeres, 44% de ellas y 61% de los hombres eran mestizos. La edad promedio al diagnóstico fue de 32 años y el tiempo medio de evolución de la enfermedad de 11 años. Un tercio terminó la escuela primaria y la mayoría pertenecía al nivel socieconómico medio. Las manifestaciones del aparato locomotor y dermatológicas fueron las más frecuentes como presentación y evolución de la enfermedad. El 60% mostró compromiso renal, siendo la glomerulonefritis tipo 4 el hallazgo histopatológico prevalente. Las causas de óbito fueron septicemia y hemorragia alveolar principalmente, asociados a SLICC más alto, anti-DNA (+), leucopenia, nivel socioeconómico medio y bajo y raza mestiza como marcadores de mal pronóstico. Conclusiones: En esta serie predominaron sexo femenino, raza mestiza, nivel socioeconómico medio y nivel de instrucción primario. Los síntomas de presentación fueron osteoarticulares y dérmicos. Las causas de muerte fueron infecciones o hemorragia alveolar. Fueron factores de mal pronóstico: anti-DNA, leucopenia, etnia mestiza y bajo nivel socioeconómico
Objective: to analyze demographic and clinical characteristics in SLE patients from a university hospital in Córdoba. Patients and Methods: We analyzed retrospectively 303 adult SLE patients assisted between 1987 and 2017 who met ACR1982 SLE criteria. Demographic, clinical and laboratory data and causes of death, hospitalization and treatments were analyzed with excel, infostat and SPSS for Windows. Results: 92% were women (race: women 44% mestizo; men 61% mestizo; mean age at diagnosis: 32 years, mean time of evolution 11 years). 1/3 of them finished primary school and most of them had medium socioeconomic status. Musculoskeletal and skin involvement was most frequent as presentation symptom and during the evolution of disease. 60% had renal involvement being type 4 glomerulonephritis the most prevalent histopathological finding. Causes of death were septicemia and alveolar hemorrhage, associated with higher SLICC, anti-DNA (+), leucopenia, low socioeconomic status and mestizo race as markers of poor prognosis. Conclusion: Female gender, mestizo race, medium socioeconomic status and primary level of education predominated in this series. Presentation symptoms were musculoskeletal and skin involvement. Causes of death were infections or alveolar hemorrhage. Anti-DNA (+), leucopenia, low socioeconomic status and mestizo race were markers of poor prognosis
Assuntos
Sinais e Sintomas , Lúpus Eritematoso SistêmicoRESUMO
To evaluate disease characteristics of childhood onset SLE in Latin America and to compare this information with an adult population in the same cohort of GLADEL. A protocol was designed as a multicenter, multinational, inception cohort of lupus patients to evaluate demographic, clinical, laboratory and serological variables, as well as classification criteria, disease activity, organ damage and mortality. Descriptive statistics, chi square, Fisher's exact test, Student's t test and multiple logistic regression were used to compare childhood and adult onset SLE. 230 patients were <18 years and 884 were adult SLE patients. Malar rash, fever, oral ulcers, thrombocytopenia and hemolytic anemia and some neurologic manifestations were more prevalent in children (p<0.05). On the other hand, myalgias, Sjögren's syndrome and cranial nerve involvement were more frequently seen in adults (p<0.05). Afro-Latin-American children had a higher prevalence of fever, thrombocytopenia and hemolytic anemia. White and mestizo children had a higher prevalence of malar rash. Mestizo children had a higher prevalence of cerebrovascular disease and cranial nerve involvement. Children met SLE ACR criteria earlier with higher mean values than adults (p: 0.001). They also had higher disease activity scores (p: 0.01), whereas adults had greater disease damage (p: 0.02). In Latin America, childhood onset SLE seems to be a more severe disease than adults. Some differences can be detected among ethnic groups.
Assuntos
Lúpus Eritematoso Sistêmico , Adolescente , Adulto , Idade de Início , Criança , Feminino , Humanos , América Latina/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , MasculinoRESUMO
Argentine population genetic structure was examined using a set of 78 ancestry informative markers (AIMs) to assess the contributions of European, Amerindian, and African ancestry in 94 individuals members of this population. Using the Bayesian clustering algorithm STRUCTURE, the mean European contribution was 78%, the Amerindian contribution was 19.4%, and the African contribution was 2.5%. Similar results were found using weighted least mean square method: European, 80.2%; Amerindian, 18.1%; and African, 1.7%. Consistent with previous studies the current results showed very few individuals (four of 94) with greater than 10% African admixture. Notably, when individual admixture was examined, the Amerindian and European admixture showed a very large variance and individual Amerindian contribution ranged from 1.5 to 84.5% in the 94 individual Argentine subjects. These results indicate that admixture must be considered when clinical epidemiology or case control genetic analyses are studied in this population. Moreover, the current study provides a set of informative SNPs that can be used to ascertain or control for this potentially hidden stratification. In addition, the large variance in admixture proportions in individual Argentine subjects shown by this study suggests that this population is appropriate for future admixture mapping studies.
Assuntos
Indígenas Sul-Americanos/genética , Povo Asiático/genética , Teorema de Bayes , População Negra/genética , Frequência do Gene , Marcadores Genéticos , Variação Genética , Genética Populacional , Humanos , Americanos Mexicanos/genética , População Branca/genéticaRESUMO
BACKGROUND: Among the diverse number of antibodies observed in systemic lupus erythematosus, antibodies against double stranded DNA (anti-dsDNA) represent important serologic markers for the disease diagnosis and the follow-up of the disease activity. OBJECTIVE: To evaluate the role of a new quantitative methodology to detect antibodies against double stranded DNA in systemic lupus erythematosus and its association with the disease activity. MATERIAL AND METHODS: The performance of the indirect immunofluorescence flow cytometry with Crithidia luciliae as substrate was compared with the Crithidia luciliae indirect immunofluorescence assay and the ELISA technique in order to detect antibodies against double stranded DNA in 54 sera from 47 patient with systemic lupus erythematosus and 100 sera from normal controls. RESULTS: The new method showed a sensitivity of 78% and a specificity of 81% when the Crithidia luciliae indirect immunofluorescence assay was the gold standard. Compared with the ELISA technique, the flow cytometry showed a sensitivity of 78% and a specificity of 86%. No correlation was found among antibodies against double stranded DNA values detected with flow cytometry and the MEX-SLEDAI activity scores. However, the flow cytometry showed a sensitivity of 70% and a specificity of 42% to distinguish patients with systemic lupus erythematosus with and without activity (MEX-SLEDAI score > or = 5). The Rho intra-observer coefficient was 0.61 (p < 0.0001). CONCLUSIONS: In spite of the fact that this new method might represent an interesting advance for antibodies against double stranded DNA quantitative testing, a clear superiority does not emerge when it was compared with more traditional assays. Difficulties related with its reproducibility might represent a limitation in the routine use of this new method.
Assuntos
Autoanticorpos/sangue , DNA/imunologia , Citometria de Fluxo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against intracellular components, the formation of immune complexes, and inflammation in various organs, typically the skin and kidney glomeruli. The etiology of the disease is not well understood but is most likely the result of the interaction between genetic and environmental factors. In order to identify susceptibility loci for SLE, we have performed genome scans with microsatellite markers covering the whole genome in families from Argentina, Italy, and Europe. The results reveal a heterogeneous disease with different susceptibility loci in different family sets. We have found significant linkage to chromosome 17p12-q11 in the Argentine set of families. The maximum LOD score was given by marker D17S1294 in combination with D17S1293, when assuming a dominant inheritance model (Z = 3.88). We also analyzed a repeat in the promoter region of the NOS2A gene, a strong candidate gene in the region, but no association was found. The locus on chromosome 17 has previously been identified in genetic studies of multiple sclerosis families. Several other interesting regions were found at 1p35, 1q31, 3q26, 5p15, 11q23 and 19q13, confirming previously identified loci for SLE or other autoimmune diseases.
Assuntos
Cromossomos Humanos Par 17/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Adulto , Idoso , Argentina/epidemiologia , Mapeamento Cromossômico , Europa (Continente)/epidemiologia , Feminino , Genótipo , Humanos , Itália/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Linhagem , Regiões Promotoras GenéticasRESUMO
Objetivos: Determinar la prevalencia de hiperhomocisteinemia (hiperhcy) en pacientes con lupus eritematoso sistémico (LES) con y sin síndrome antifosfolípido (SAF); comparar los niveles de homocisteína (Hcy) entre pacientes con LES (con y sin SAF asociado) y un grupo de controles sanos y determinar la correlación entre hiperhcy y la presencia de anticuerpos antifosfolípidos. Pacientes y métodos: Se estudiaron 44 ptes con LES, portadores o no de SAF. Se los dividió en 2 grupos: 17 con LES y SAF y 27 con LES sin SAF y se compararon con 24 controles sanos. A todos se les realizó interrogatorio, examen físico y pruebas de laboratorio: anticuerpos anticardiolipinas (aCL), anticoagulante lúpico y Hcy. Se consideró hiperhcy a valores superiores a 9. A los ptes con hiperhcy se los trató con ácido fólico + B6 + B 12 durante un mes. Análisis estadístico: variables cualitativas: Chi cuadrado o Exacta de Fischer y cuantitativas: test T de Student o MannWhitney test. Resultados y conclusiones: Hubo 35 manifestaciones trombóticas en los 44 pacientes. Se encontró Hiperhcy en 27 ptes con LES (61,4%), de los cuales 12 tenían SAF. La diferencia entre los valores de Hcy de los pacientes con o sin SAF no fue significativa (p=0,42). Comparando las concentraciones de Hcy entre pacientes y controles, la diferencia fue muy significativa (p=0,002).También tuvo significación estadística la diferencia entre las concentraciones de Hcy de los pacientes con LES sin SAF vs. controles (p=0,015) y LES con SAF vs. controles (p=0,003). A 33 ptes se les dosó aCL: 20 (60,6%) fueron (+). De estos, 15 (75%) tenían hiperhcy. De los 27 pacientes con LES que tenían hiperhcy, sólo 18 cumplieron con el mes de tratamiento con a.fólico+B6+B12. 16 de 18 (88,8%) normalizaron o disminuyeron la Hcy.
Objectives: to detect the prevalence of hyperhcy in SLE patients with and without antiphospholipid syndrome; to compare the Hcy levels between those patients and healthy controls and to determine the correlation between hyperhcy and antiphospholipid antibodies. Patients and methods: we studied 44 SLE patients: 17 had antiphospholipid syndrome and 27 didn't have it, and we compared tbem to 24 healthy controls. All of them where checked clinically and with laboratory tests like anticardiolypin antibodies, lupus anticoagulant and Hcy. Hcy > 9 was considered abnormal. Patient who had hyperhcy were treated with folic acid+vitB6+vitBI2 a month along. Statistical analysis: qualitative variables: chi square or Fischer's; quantitative variables: Student's T test or Mann-Whitney's test. Results and conclusions: there were 35 trombotic manifestations in 44 patients. Hyperhcy was present in 27 SLE patients (61,4%), 12 of them had antiphospholipid syndrome. Hcy concentrations patients vs. controls was statisticaly different (p=0,002). There was also statistically different the hcy concentration from SLE patients with SAF vs controls (p=0,003) and without SAF vs controls (p= 0,015). From 33 SLE patients, 20 (33%) were aCL( +). 15(75%) of them had hiperhcy.
Assuntos
Humanos , Masculino , Feminino , Gravidez , Adulto , Pessoa de Meia-Idade , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/complicações , Hiper-Homocisteinemia , Homocisteína/sangue , Lúpus Eritematoso Sistêmico , Trombose/etiologia , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/epidemiologia , Argentina/epidemiologia , Biomarcadores , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/complicações , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Fatores de RiscoRESUMO
Com o objetivo de avaliar a ocorrência de anticorpos antineutrófilos citoplasmáticos (cANCA) e anticorpos antineutrófilos perinucleares (pANCA), foram estudadas amostras de soro de 100 pacientes com doenças do tecido conjuntivo (DDTC) sendo 38 com lúpus eritematoso sistêmico (LES), 23 com artrite reumatóide (AR), 13 com doença mista do tecido conjuntivo (DMTC), 12 com esclerose sistêmica (PSS), 1 com arterite de takayasu (AT), 2 com poliarterite nodosa (PAN), 2 com granulomatose de Wegener (GN), 2 com CREST, 2 com síndrome de Sjögren (SS), 3 com vasculite leucocitoclástica (VL), 1 com eritema nodoso (EN), 1 com polimiosite (PM) e 25 voluntários normais. O cANCA e pANCA foram identificados por imunofluorescência indireta (IFI), de acordo com as normas do International First Workshop of ANCA (1983) com amostras diluídas em 1:20 no soro e neutrófilos fixados com etanol absoluto. Foi detectado o cANCA em 6 pacientes. Obtiveram-se títulos elevados de cANCA (>1/320) em GW (n=2) e títulos baixos (de 1/40 a 1/320) em AR (n=1), PAN (n=1), ESP (n=1) e LV (N=1). Observou-se pANCA em 29 pacientes: TA (n=1), SLE (n=19), RA (n=2), PSS (n=1) e MCTD (n=6). Os dados mostram frequência elevada de cANCA em GW, apesar de o pequeno número de casos impossibilitar determinar a sensibilidade e especificidade diagnóstica
Assuntos
Humanos , Masculino , Feminino , Anticorpos Anticitoplasma de Neutrófilos , Tecido Conjuntivo , Granulomatose com PoliangiiteRESUMO
INTRODUCTION: There are no medical publications with economic analysis of rheumatoid arthritis patients (RA) from Argentina are lacking. The objective of the present study is to determine the direct cost and its breakdown in patients with RA. MATERIAL AND METHODS: Fifty-two patients who met the American College of Rheumatology RA criteria were included. Direct cost was calculated over a follow-up period of 6 months during year 2001. Variables were analyzed with Student's T test, Mann-Whitney U Test, c' or ANOVA as corresponded. P values < 0.05 were considered significant. RESULTS: The mean monthly home income was $426.6 SD 272. The mean half-yearly direct costs was $677.5 SD 376.2. The components of the direct cost were identified and the mean for medication cost was $606.7 (89 per cent), for lab tests was $45.5 (7 per cent), for medical attention $12.5 (2 per cent) and other costs $2.4. No differences in total cost or in medication cost were found when compared considering age, evolution time of RA or HAQ scores. CONCLUSION: Half-yearly direct cost in RA is excessively high considering the monthly mean income of the patients being analyzed. The cost of medication was the principal component of the direct cost.