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Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well identified as risk factors. SLE patients present different clinical phenotypes, which are partly explained by admixture patterns variation among Mexicans. Population genetic has insight into the high genetic variability of Mexicans, mainly described through HLA gene studies with anthropological and biomedical importance. A prospective, case-control study was performed. In this study, we recruited 146 SLE patients, and 234 healthy individuals were included as a control group; both groups were admixed Mexicans from Mexico City. The HLA typing methods were based on Next Generation Sequencing and Sequence-Based Typing (SBT). The data analysis was performed with population genetic programs and statistical packages. The admixture estimations based on HLA-B and -DRB1 revealed that SLE patients have a higher Southwestern European ancestry proportion (48 ± 8%) than healthy individuals (30 ± 7%). In contrast, Mexican Native American components are diminished in SLE patients (44 ± 1%) and augmented in Healthy individuals (63 ± 4%). HLA alleles and haplotypes' frequency analysis found variants previously described in SLE patients from Mexico City. Moreover, a conserved extended haplotype that confers risk to develop SLE was found, the HLA-A∗29:02â¼C∗16:01â¼B∗44:03â¼DRB1∗07:01â¼DQB1∗02:02, pC = 0.02, OR = 1.41. Consistent with the admixture estimations, the origin of all risk alleles and haplotypes found in this study are European, while the protection alleles are Mexican Native American. The analysis of genetic distances supported that the SLE patient group is closer to the Southwestern European parental populace and farthest from Mexican Native Americans than healthy individuals. Heterogeneity of genetic admixture determines SLE susceptibility and protection in Mexicans. HLA sequencing is helpful to determine susceptibility alleles and haplotypes restricted to some populations.
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INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well-identified as risk factors. SLE patients have different phenotypes or clinical presentations, which vary among Mexicans. This variation could be explained by ethnicity and admixture. Since socioeconomic status probably limits and change the patterns of migration, this factor could favor inbreeding and homogamy in some geographic areas. Consequently, it could alter or restrict the possibilities of admixture too. Therefore, the socioeconomic status may also have implications in the susceptibility and the clinical heterogeneity of SLE in Mexican patients. METHODS: One hundred twenty-three SLE patients and 234 healthy individuals with Mexican admixed ancestry were recruited. HLA alleles were analyzed using the HLA typing method based on Sequence-based typing (SBT). RESULTS: As expected, it was found an increased frequency of the HLA-DRB1*03:01 allele in all socioeconomic groups when compared with healthy individuals. The susceptibility allele found in the low-income SLE patients was HLA-DRB1*04:05 whereas, the susceptibility alleles for the high-income SLE patients were HLA-DRB1*07:01 (pC = 0.03, OR = 2.0) and HLA-DRB1*11:04 (pC = 0.0004, OR = 5.1). Additionally, the frequencies of two protective alleles HLA-DRB1*14:06 (pC = 0.01, OR = 0.28) and HLA-DRB1*16:02 (pC = 0.04, OR = 0.22) were found diminished. These findings correlate with the admixture differences between low-income and high-income SLE patients. The clinical manifestations showed a different distribution between both groups. Arthritis and neurological disorder were prevalent in low-income SLE patients, while the hematological disorder was prevalent in high-income SLE patients. CONCLUSIONS: These findings suggest that HLA class II DRB1 genes contribute to the susceptibility and protection to develop SLE differently depending on socioeconomic status. Due to this, the clinical manifestations vary among patients and it could be related to different admixture charge.Key Point⢠HLA class II DRB1 genes contribute to the susceptibility and protection to develop SLE differently depending on socioeconomic status.
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Predisposición Genética a la Enfermedad , Cadenas HLA-DRB1/genética , Renta , Lupus Eritematoso Sistémico/genética , Clase Social , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Fenotipo , Adulto JovenRESUMEN
To evaluate the association of C-reactive protein (CRP) polymorphisms with risk of development SLE in a group of Mexican individuals. Five CRP polymorphisms (rs3093059, rs3093062, rs1800947, rs1130864, and rs1205) were determined by PCR-restriction fragment length polymorphism and SNP rs3093061 by refractory mutation system PCR assay in 126 SLE patients and 131 controls. Four of the polymorphisms showed differences between patients and controls. rs3093061 polymorphism was associated with a lower risk of developing lupus principally in the codominant 2 (OR = 0.219, 95% CI 0.108-0.785, P = 0.015) model. rs1130864 was associated with decreased risk mainly under codominant 1 (OR = 0.288, 95% CI 0.143-0.581, P = 0.001) model. rs1205 was associated under the over-dominant model (OR = 0.504, 95% CI 0.270-0.942, P = 0.032). The rs3091244 polymorphism was associated with decreased risk of SLE mostly under additive (OR = 0.605, 95% CI 0.393-0.931. P = 0.022) model. Our study establishes that rs3093061, rs1130864, rs1205, and rs3091244 polymorphisms are associated with decreased risk of developing SLE.
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Proteína C-Reactiva/genética , Predisposición Genética a la Enfermedad , Haplotipos , Lupus Eritematoso Sistémico/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/etnología , Masculino , México/etnología , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido SimpleRESUMEN
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.
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Genes Codificadores de la Cadena beta de los Receptores de Linfocito T , Lupus Eritematoso Sistémico/sangre , Linfocitos T , Estudios de Casos y Controles , Femenino , Genes Codificadores de la Cadena beta de los Receptores de Linfocito T/genética , Humanos , Lupus Eritematoso Sistémico/genética , MasculinoRESUMEN
BACKGROUND: P-gp and BCRP1 are transporter proteins that may confer drug resistance. OBJECTIVE: To compare P-gp and BCRP1 function in rheumatoid arthritis patients with active and inactive disease and to define their relation with disease activity. METHODS: We included 17 active patients paired (age, gender, disease duration) to 17 inactive patients. All had baseline evaluations and 27 had additional six-month follow-up. P-gp and BCRP1 functional activity was measured in peripheral mononuclear cells by flow cytometry. Percentage of lymphocytes able to extrude substrates for P-gp and BCRP1 were recorded in the presence/absence of selective inhibitors. Informed consent was obtained. Descriptive statistics and linear regression model were applied. RESULTS: Active patients had higher efflux function of both transporters than inactive patients: median (25-75 IQR) P-gp of 7.1% (1.4-29.3) vs. 1.6% (0.7-3.5), p = 0.02 and BCRP1 of 6.2% (1.3-22.4) vs. 1.3% (0.7-2), p = 0.007. At baseline, disease activity was the only predictor of both transporter functions. At follow-up, changes in disease activity correlated with shift in P-gp (r = 0.35, p = 0.07) and BCRP1 (r = 0.33, p=0.09) function. CONCLUSIONS: Patients with active rheumatoid arthritis had a higher efflux function of P-gp and BCRP1 compared to inactive patients. The behavior of P-gp and BCRP1 appeared to be conditioned by disease activity.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Corticoesteroides/administración & dosificación , Antirreumáticos/administración & dosificación , Artritis Reumatoide/metabolismo , Proteínas de Neoplasias/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Corticoesteroides/metabolismo , Adulto , Antirreumáticos/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Estudios de Casos y Controles , Daunorrubicina/administración & dosificación , Daunorrubicina/metabolismo , Resistencia a Múltiples Medicamentos , Femenino , Humanos , Linfocitos/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To compare drug efflux function of ABCB1 and ABCG2 transporters in rheumatoid arthritis (RA) patients with active disease and in remission. METHODS: Twenty two active RA patients (DAS28 ≥3.2) and 22 patients in remission (DAS28<2.6) were selected from an early RA clinic. All patients were evaluated at study inclusion and six months later. ABCB1 and ABCG2 functional activity was measured in peripheral lymphocytes by flow cytometry. The percentage of cells able to extrude substrates for ABCB1 and ABCG2 was recorded. RESULTS: Active patients had higher ABCB1 and ABCG2 activity compared with patients in remission (median [interquartile range]): 3.9% (1.4-22.2) vs (1.3% (0.6-3.2), p = 0.003 and 3.9% (1.1-13.3) vs 0.9% (0.5-1.9) p = 0.006 respectively. Both transporters correlated with disease activity assessed by DAS28, rho = 0.45, p = 0.002 and rho = 0.47, p = 0.001 respectively. Correlation was observed between the time from the beginning of treatment and transporter activity: rho = 0.34, p = 0.025 for ABCB1 and rho = 0.35, p = 0.018 for ABCG2. The linear regression model showed that DAS28 and the time from the onset of treatment are predictors of ABCB1 and ABCG2 functional activity, even after adjustment for treatment. After six months we calculated the correlation between change in DAS28 and change in the functional activity in both transporters and found a moderate and significant correlation for ABCG2 (rho = 0.28, p = 0.04) and a non-significant correlation for ABCB1 (rho = 0.22, p = 0.11). CONCLUSIONS: Patients with active RA have an increased function of ABCB1 and ABCG2, and disease activity is the main determinant of this phenomena.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Artritis Reumatoide/metabolismo , Proteínas de Neoplasias/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Adulto , Artritis Reumatoide/diagnóstico , Transporte Biológico , Daunorrubicina/metabolismo , Demografía , Femenino , Citometría de Flujo , Estudios de Seguimiento , Humanos , Modelos Lineales , Masculino , Mitoxantrona/metabolismo , Inducción de Remisión , Adulto JovenRESUMEN
Primary Sjögren syndrome (PSS) is a chronic autoimmune disease characterized by sicca complex and various systemic manifestations. Although it is well accepted to use corticosteroids for the treatment of systemic manifestations, there is scarce information available regarding the use of targeted therapy for refractory cases. We describe a case of a severe PSS patient refractory to conventional treatment with a response to bortezomib, a proteasome inhibitor commonly used for the treatment of multiple myeloma. Bortezomib administration resulted in a notable improvement of the general symptoms, particularly fatigue, and a decrease in serum globulin levels as well as in serum viscosity. Hyperglobulinemic purpura disappeared, and prednisone tapering succeeded. Because of chronicity, no clinical changes were observed in sicca symptoms. As far as we know, this is the first report on the use of bortezomib in a refractory case of PSS.
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Ácidos Borónicos/uso terapéutico , Resistencia a Medicamentos , Inhibidores de Proteasoma/uso terapéutico , Pirazinas/uso terapéutico , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Adulto , Ácidos Borónicos/efectos adversos , Bortezomib , Fatiga/tratamiento farmacológico , Fatiga/epidemiología , Fatiga/etiología , Femenino , Globulinas/metabolismo , Humanos , Incidencia , Inhibidores de Proteasoma/efectos adversos , Pirazinas/efectos adversos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/metabolismo , Resultado del TratamientoRESUMEN
Hyperprolactinemia has been related to autoimmune diseases. Herein, we describe a case of a female with a prolactin producer pituitary macroadenoma who developed severe polymyositis one month after its removal. The patient had very high levels of CPK and muscle biopsy showed remarkable inflammatory infiltration. Steroid therapy was followed with total recovery. To the best of our knowledge, this is the first case reported of acute polymyositis after pituitary macroadenoma exeresis.
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We have identified Tspan33 as a gene encoding a transmembrane protein exhibiting a restricted expression pattern including expression in activated B cells. TSPAN33 is a member of the tetraspanin family. TSPAN33 is not expressed in resting B cells, but is strongly induced in primary human B cells following activation. Human 2E2 cells, a Burkitt's lymphoma-derived B cell model of activation and differentiation, also upregulate TSPAN33 upon activation. TSPAN33 is expressed in several lymphomas including Hodgkin's and Diffuse large B cell lymphoma. TSPAN33 is also expressed in some autoimmune diseases where B cells participate in the pathology, including rheumatoid arthritis patients, systemic lupus erythematosus (SLE), and in spleen B cells from MRL/Fas(lpr/lpr) mice (a mouse model of SLE). We conclude that TSPAN33 may be used as a diagnostic biomarker or as a target for therapeutic antibodies for treatment of certain B cell lymphomas or autoimmune diseases.
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Linfocitos B/efectos de los fármacos , Lupus Eritematoso Sistémico/inmunología , Tetraspaninas/inmunología , Animales , Linfocitos B/inmunología , Linfocitos B/patología , Biomarcadores/metabolismo , Estudios de Casos y Controles , Línea Celular , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Lipopolisacáridos/farmacología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/patología , Activación de Linfocitos , Masculino , Ratones , Ratones Transgénicos , Especificidad de Órganos , Cultivo Primario de Células , Transducción de Señal , Acetato de Tetradecanoilforbol/farmacología , Tetraspaninas/genéticaRESUMEN
BACKGROUND: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by B-cell hyper-reactivity and the production of pathogenic anti-nuclear-directed auto-antibodies (Abs). B-cell ontogeny is partly dependent on the CXCL12/CXCR4 axis for which the contribution to SLE pathogenesis remains unclear. CXCR7, the novel receptor for CXCL12, is differentially expressed among memory B-cell subsets. However, its biological role in SLE remains to be explored. METHODS: Relative CXCR4 and CXCR7 expression levels were compared by quantitative PCR in leukocytes from blood samples of 41 Mexican Mestizos patients with SLE and 45 ethnicity-matched healthy subjects. Intracellular and membrane expression of both receptors was analyzed by flow cytometry in naive and Ab-secreting B cells. B-cell responsiveness to CXCL12 was investigated using Transwell-based chemotaxis assays. Data were analyzed using the Kruskal-Wallis test for comparisons of values amongst healthy controls and patients with inactive or active SLE, and non-parametrically using the Mann-Whitney U-test for multiple comparisons and unpaired samples. Correlations were determined by Spearman's ranking. RESULT: SLE leukocytes displayed reduced levels of CXCR4 and CXCR7 transcripts. In SLE patients, a significant defect in CXCR4 expression was detected at the surface of naive and Ab-secreting B cells, associated with an abnormal intracellular localization of the receptor. CXCR7 predominantly localized in cytosolic compartments of B cells from healthy and SLE individuals. Disease activity did not impact on these expression patterns. Altered receptor compartmentalization correlated with an impaired CXCL12-promoted migration of SLE B cells. CONCLUSIONS: Our data highlight a down-regulation of CXCL12 receptors on circulating B cells from SLE patients that likely influences their migratory behavior and distribution.
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Linfocitos B/metabolismo , Etnicidad , Lupus Eritematoso Sistémico/metabolismo , Lupus Eritematoso Sistémico/patología , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Adulto , Linfocitos B/efectos de los fármacos , Linfocitos B/patología , Recuento de Células , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Quimiocina CXCL12/farmacología , Quimiotaxis/efectos de los fármacos , Demografía , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/genética , Masculino , México , Persona de Mediana Edad , Células Plasmáticas/efectos de los fármacos , Células Plasmáticas/metabolismo , Células Plasmáticas/patología , Receptores CXCR/genética , Receptores CXCR4/genética , Adulto JovenRESUMEN
The aim of this study was to investigate the possible role of the CCR5 59029 AâG promoter point mutation polymorphism in determining the susceptibility to rheumatoid factor-positive and rheumatoid factor-negative rheumatoid arthritis. This polymorphism was assessed in 85 seropositive and 39 seronegative rheumatoid arthritis patients and in 126 healthy individuals of the same geographic and ethnic origin. We found an increase in the genetic frequency of the A allele in the 59029 AâG promoter region of the CCR5 receptor in patients with rheumatoid arthritis compared with healthy controls (p = 0.01; OR = 1.5, 95% CI (1.0-2.2). Likewise, the homozygous state for the A allele was found to be more frequent in rheumatoid arthritis patients, again when compared with healthy controls (p = 0.03; OR = 1.8, 95% CI 1.0-3.0). The increased frequency of the A allele was more evident in the more benign, seronegative rheumatoid arthritis group when compared with controls (p = 0.003; OR 2.4 95% CI 1.3-4.4), and when combining the A homozygous and the AG heterozygous patients compared with healthy subjects. These results suggest that this CCR5 promoter polymorphism seems to play an important role in determining different clinical courses in both forms of rheumatoid arthritis.
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Artritis Reumatoide/genética , Regiones Promotoras Genéticas , Receptores CCR5/genética , Factor Reumatoide/sangre , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/inmunología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
Systemic lupus erythematosus is a serious autoimmune disease that causes significant morbidity and mortality. It is also a disease for which several clinical differences among ethnic groups have been documented. Until recently, Hispanics, as separate patient cohort, had not been included in these studies. As a result, there is currently little information concerning its characteristics both at the clinical and at the molecular levels. With the currently available data, we can ascertain that this population exhibits considerable heterogeneity, in which some genetic mutations have been detected that may confer greater susceptibility and/or protection against the disease. The important differences in the clinical manifestations include a higher rate of renal complications as well as greater mortality. The latter may be due, at least in part, to lower socio-economic levels and inappropriate access to health care. However, given the limited data available that have focused on potential molecular mechanisms that may affect the Hispanic population affected with lupus, we cannot conclude that all the differences in disease outcome, complications, and severity that affect this patient population may be due to sociological factors. We conclude that more research is required to evaluate potential genetic and molecular factors that affect Hispanic lupus patients.
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Hispánicos o Latinos/genética , Lupus Eritematoso Sistémico/etnología , Lupus Eritematoso Sistémico/genética , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Incidencia , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , PrevalenciaRESUMEN
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme which suppresses T lymphocyte activity and induces Foxp3+ CD4+ regulatory T cells (Tregs) polarisation. The aim of this study was to evaluate the expression of IDO in freshly isolated peripheral cells as well as to enumerate Tregs and Th17 subpopulation in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. MATERIALS AND METHODS: The percentage of IDO-expressing cells as well as Tregs and Th17 was evaluated in 14 active RA- (aRA), 13 inactive RA- (iRA), 7 aSLE-, 12 iSLE-treated patients and 11 healthy donors (controls). Intracellular IDO was analysed by flow cytometry in CD14+, CD8α+, CD16+ and CD123+ cell subpopulations. Tregs and Th17 were assessed by intracellular of Foxp3 and IL17A detection in CD4+ CD14- cells. A total of 50,000 events were recorded for each sample. RESULTS: The amounts of CD14+/CD16-/IDO+, CD14-/CD16+/IDO+ and CD14+/CD16+/IDO+-expressing peripheral cells were slightly lower in inactive vs. active disease in RA and SLE patients. Notwithstanding, only inactive patients had statistically significant lower percentages when compared to controls. aRA and iRA showed a statistically significant decrease in CD8α+/CD123+/IDO+ vs. controls. Meanwhile, only iSLE patients had lower CD8α+/CD123+/IDO+ cells vs. aSLE patients and controls. Th17 subset was present in higher amounts in aRA and iRA patients vs. controls. Tregs showed an increase in aRA patients vs. controls. CONCLUSIONS: A decreased percentage of IDO-expressing peripheral cells were determined in iRA and iSLE compared to controls. It could play a critical role in tolerance loss in these diseases.
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Artritis Reumatoide/inmunología , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Lupus Eritematoso Sistémico/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Adulto , Anciano , Antígenos CD8/inmunología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Citometría de Flujo , Humanos , Receptores de Lipopolisacáridos/inmunología , Masculino , Persona de Mediana Edad , Receptores de IgG/inmunología , Estadística como Asunto , Adulto JovenAsunto(s)
Artritis Reumatoide/complicaciones , Artritis/etiología , Lupus Eritematoso Sistémico/complicaciones , Osteólisis/etiología , Adulto , Antirreumáticos/uso terapéutico , Artritis/diagnóstico , Artritis/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Comorbilidad , Femenino , Humanos , Lupus Eritematoso Sistémico/epidemiología , Metotrexato/uso terapéutico , Osteólisis/diagnóstico , Osteólisis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
We report two cases of long-term juvenile idiopathic arthritis which developed recurrent subglottic stenosis secondary to localized Wegener's granulomatosis. In both cases, the biopsies taken from the affected region shown granulomatous vasculitis with multinucleated giant cells. Both patients presented positive serology for antineutrophil cytoplasmic antibodies by immunofluorescence (c-ANCA) and ELISA (PR3). The involvement or other organs was ruled out at the time of Wegener's granulomatosis diagnosis and during follow-up. To our knowledge, this is the first report of the association between juvenile idiopathic arthritis and a localized form of Wegener's granulomatosis.
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Artritis Juvenil/complicaciones , Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/etiología , Adulto , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Biopsia , Femenino , Granulomatosis con Poliangitis/sangre , Humanos , Masculino , Factores de Tiempo , Vasculitis/patologíaRESUMEN
In the present study, we report the clinical characteristics of a unique systemic lupus erythematosus (SLE) multiplex family with 6 of its members affected by the disease, 1 of them being male. Four patients showed nephropathy, 2 of them with late-onset SLE (52 and 55-year-old), one with cutaneous and articular involvement, and another one developing lupus after 5 years undergoing highly active antiretroviral therapy (HAART) due to acquired immunodeficiency syndrome. Notwithstanding the genetic load, the fact that 2 patients showed late-onset disease, and the extreme delay of the appearance of SLE after HAART in the proband suggest that not only genetic, but other--mainly environmental--factors are necessarily required for the development of SLE.
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Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Lupus Eritematoso Sistémico/genética , Linaje , Adolescente , Adulto , Edad de Inicio , Femenino , Humanos , Enfermedades Renales/etiología , Lupus Eritematoso Sistémico/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
A 39-year-old woman developed systemic lupus erythematosus with nephropathy after a holiday in Jamaica. She was prescribed with prednisone, azathioprine and aspirin. As she was obsessed with aesthetic procedures, she decided not to take the prescription. Instead, she took her bodybuilding trainer's advice of one intramuscular injection of stanozolol for 10 weeks in order to increase her gluteus area. One week after finishing the latter regimen, there was no disease activity. Whether lupus remission in this patient was spontaneous or a consequence of stanozolol administration will remain a riddle for this fortunate outcome.
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Anabolizantes/administración & dosificación , Doping en los Deportes/métodos , Nefritis Lúpica/tratamiento farmacológico , Estanozolol/administración & dosificación , Adulto , Femenino , Humanos , Inyecciones Intramusculares , Nefritis Lúpica/complicaciones , Cooperación del Paciente , Inducción de Remisión , Trastornos Somatomorfos/complicaciones , Trastornos Somatomorfos/tratamiento farmacológico , Negativa del Paciente al Tratamiento , Levantamiento de PesoRESUMEN
Multidrug resistance-1 (MDR-1) is characterized by overfunction of P-glycoprotein (P-gp), a pump molecule that decreases intracellular drug concentration by effluxing them from the intracellular space. Broad ranges of structurally unrelated compounds are transported by P-gp, including antineoplastic agents, HIV protease inhibitors, prednisone, gold salts, methotrexate, colchicine as well as several antibiotics. In contrast, many other compounds such as calcium channel blockers (verapamil) and immunosupressors (cyclosporine-A) are able to inhibit P-gp function. The P-gp role in therapeutic failures has been extensively studied in cancer; however, there is little information regarding MDR-1 phenotype in autoimmune disorders. It has been reported that an increased number of lymphocytes are able to extrude P-gp substrates in rheumatoid arthritis, immune thrombocytopenic purpura and systemic lupus erythematosus, the patients with poor response to treatment being the ones that exhibit the highest values. This may be due, at least in part, to a simultaneous long-term usage of several drugs that induce P-gp function. Since abnormally activated cell compartments characterize autoimmune diseases, it is possible that those cells are the ones that exhibit drug resistance. The study of drug resistance mechanisms in autoimmunity may be helpful for the optimization of the current therapeutic schemes through their combination with low doses of P-gp inhibitors.