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Artritis Reumatoide. Bases Moleculares, Clínicas y Terapéuticas
... años, un promedio de tres radiografías de manos y pies. La artritis reumatoidea (AR) es una enfermedad crónica autoinmune e inflamatoria que compromete las articulaciones que tienen movimiento (Anaya et al. 2006). Afecta principalmente a las mujeres entre la cuarta y quinta décadas de la vida. ...
... Con frecuencia compromete otros órganos distintos a las articulaciones. Dadas las características mencionadas, la AR tiene un impacto adverso en la esfera biopsicosocial y su costo es alto (Anaya et al. 2006). Para la estimación de las funciones de intensidad (α LM , α MS ) se incluyó la covariable ausencia o presencia de la secuencia del Share Epitope (SE): 0 = No, 1 = Sí. ...
We consider a three state model with an absorbing state assuming an underlying Markov process to explain the dependence among observations within subjects. We compare, using a simulation study, three different parameterizations of the transition intensity rate: the first one is based on the Andersen-Gill's multiplicative hazard model (Andersen et al. 1993), the second one is based on the logistic model, and the third one depends on the complementary log-log model. The method to estimate the effect of the parameters is based on the likelihood function which can be optimized using the exact solutions of a Kolmogorov forward differential equations system in conjunction with the Newton-Raphson algorithm (Abramowitz & Stegun 1972). We use the relative bias to select the best estimation estrategy. The methodology is ilustrated using longitudinal data about rheumatoid arthritis (RA) from the Corporación para Investigaciones Biológicas, CIB.
... Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease characterized by symmetric polyarthritis with progressive damage of diarthrodial joints leading to disability, increased comorbidity and premature mortality [1] . RA is a complex and heterogeneous genetic disease in which multiple genetic and non-genetic factors interact over the time [1]. ...
... Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease characterized by symmetric polyarthritis with progressive damage of diarthrodial joints leading to disability, increased comorbidity and premature mortality [1] . RA is a complex and heterogeneous genetic disease in which multiple genetic and non-genetic factors interact over the time [1]. Latin America (i.e. the geographical area defined by Mexico, Central America, South America, and the islands of the Caribbean) is a growing and foremost region with a population of about 515 million people. ...
To estimate the common effect size of HLA-DRB1 alleles on rheumatoid arthritis (RA) susceptibility across Latin America populations through a meta-analysis combining the results of published data.
Case-control studies on HLA-DRB1 association with RA in Latin America were searched up to October 2006. Genotype frequencies were extracted according to both shared epitope (SE) and HLA-DR4 positive or negative alleles. The effect summary odds ratio (OR) and 95% confidence intervals was obtained. Heterogeneity and publication bias were assessed.
Eight studies containing 684 cases and 1015 controls were included. Under the random effects model, the common OR was 3.28 (1.93, 5.60) (p<0.0001) and 3.54 (2.47, 5.05) (p=4.22 x 10(-12)) for HLA-DR4 and SE, respectively. There was no evidence of publication bias according to Funnel plot and Egger's regression test (p=0,445 for DR4 and p=0,464 for SE meta-analysis). Significant heterogeneity was observed for HLA-DR4 (I2=81.06%, Q=36.96, p=0.000005) but not for the SE meta-analysis.
HLA-DR4 and SE positive HLA-DRB1 alleles (mainly HLA-DRB10404) are associated with RA in Latin Americans. Heterogeneity is expected owing to the diverse degree of admixture between the examined populations. Our findings support the HLA as a major susceptibility locus for RA and validate the SE hypothesis in Latin America.
... años, un promedio de tres radiografías de manos y pies. La artritis reumatoidea (AR) es una enfermedad crónica autoinmune e inflamatoria que compromete las articulaciones que tienen movimiento (Anaya et al. 2006). Afecta principalmente a las mujeres entre la cuarta y quinta décadas de la vida. ...
... Con frecuencia compromete otros órganos distintos a las articulaciones. Dadas las características mencionadas, la AR tiene un impacto adverso en la esfera biopsicosocial y su costo es alto (Anaya et al. 2006). Para la estimación de las funciones de intensidad (α LM , α MS ) se incluyó la covariable ausencia o presencia de la secuencia del Share Epitope (SE): 0 = No, 1 = Sí. ...
"Se considera un modelo múltiple de tres estados donde uno de ellos es absorbente. Se asume que la dependencia entre las observaciones registradas para un mismo sujeto sigue un proceso de Markov. Se comparan, vía simulación, tres diferentes parametrizaciones de la tasa de intensidad de transición: la primera está basada en el modelo de hazard multiplicativo de Andersen- Gill (Andersen et al. 1993), la segunda, en el modelo logístico, y la tercera depende del modelo log-log complementario. El método de estimación de parámetros se basa en la función de verosimilitud la cual se optimiza usando las soluciones exactas de un sistema de ecuaciones de Kolmogorov hacia adelante junto con el algoritmo de Newton-Raphson (Abramowitz & Stegun 1972). Usando el sesgo relativo, se selecciona el mejor método de parametrización y se ilustra usando datos recopilados en la Corporación para Investigaciones Biológicas, CIB1, acerca de pacientes con artritis reumatoidea."
... Existe evidencia que demuestra que el suministro regular del medicamento induce un estado de tolerancia inmunológica, mientras que el uso irregular genera activación persistente del sistema inmunológico cada vez que se expone de nuevo al medicamento, lo cual favorece la formación de anticuerpos anti-ADL 22,23 . Esto es consistente con lo encontrado en nuestro estudio, pues hubo regularidad en el suministro del medicamento en el 47% de los pacientes que fueron anticuerpos anti-ADL+, vs. el 76% en los que fueron anticuerpos anti-ADL-, diferencia que fue estadísticamente significativa (p = 0,015). ...
Objective
To determine whether seropositivity in rheumatoid arthritis patients treated with adalimumab (ADL) is associated with the presence of anti-adalimumab (anti-ADL) antibodies.
Materials and methods
A descriptive observational study that included patients diagnosed with rheumatoid arthritis according to ACR 1987 criteria, and who were on treatment with ADL as the first biological, for at least six months. All patients were evaluated for rheumatoid factor, anti-citrulline antibodies, erythrocyte sedimentation rate, C-reactive protein, clinimetric indices, and level of anti-ADL antibodies.
Results
A total of 80 patients with a mean age of 56 years were evaluated, of whom 86% were women. The mean duration of the disease was 15 years, and the ADL exposure time was 52 months (median value). The seropositivity for rheumatoid factor tended to be higher in patients who developed anti-ADL antibodies compared to those who did not (90.5% vs. 66.1%). The magnitude of the association between rheumatoid factor and the presence of anti-ADL antibodies was shown to be strong and statistically significant (OR = 4.87, 95% CI; 1.03–23.03). Adjusted multivariate regression analyses showed a strong association (OR = 9.77, 95% CI; 1.74–54.79) between seropositivity and the presence of anti-ADL antibodies, which, given the low number of patients, lacks precision (95% CI very wide).
Conclusions
Seropositive patients tend to have more anti-ADL antibodies. However, a larger sample size is required to obtain the necessary precision and greater certainty in these findings.
Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease that is manifested in destructive polyarthritis in association with serological evidence of autoreactivity. It is characterized by chronic pain and joint destruction, premature mortality and an elevated risk of disability, with high costs for those suffering from this disease and for society. If this condition is not treated, joint destruction from bone erosion can be expected, as well as progressive inabilities, leading eventually to disability, after a time period that can vary from only a few months to many years, depending on prognostic factors. A serious consequence for those suffering from this disease is the loss of their ability to work, especially in the case of manual workers, since many of them lose their income during the first two years of their illness (1). This situation contrasts with the statement asserting that RA is currently the most common potentially-treatable cause of disability in the western world (2). This might be proven true if treatment would be given to patients during the early stages of the disease – which is recommended in order to change the paradigm of RA therapy toward the immediate application of new effective therapies or schemes combining these therapies.
New agents capable of inducing the remission of this disease have been introduced in clinical practice over the last decade. These include anti-IL1 and anti-IL6 agents, TNFα blockers, B cell depleters and regulators of lymphocyte co-stimulation.
The mechanisms underlying the control of the immune system are still incompletely solved. The treatment of many human diseases is still a medical challenge. The innate immune system recognizes the difference between self and non-self antigens through the binding of pathogen associated molecular patterns to pattern recognition receptors present on the antigen presenting cells. The recent rediscovered regulatory T cells participate in the immune system homeostasis. On the other hand, regulatory T cells may be incriminated in the pathology of both inflammatory and infectious diseases. Thus, these cells would be a suitable target for the treatment of diseases in which they are involved. The participation of regulatory T cells in some infectious diseases could explain why there is an opposite association between some infectious diseases such as tuberculosis and autoimmune diseases. As a corollary, depletion or inactivation of regulatory T cells could facilitate the development of autoimmune phenomena.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that originates from a disabling disorder. To date, the etiology of RA is unknown. However, the existence of genetically susceptible individuals was considered. Many studies have been performed worldwide, for example, in Poland, Argentina, Chile, Mexico, Brazil, and Colombia, among others, regarding the influence between HLA-DR alleles and disease, but not in Ecuador.
The aim of this study was to determine the involvement of Class I and II HLA alleles in patients with RA.
This study was conducted in 30 adult patients with RA previously diagnosed, according to the classification criteria of the American College of Rheumatology (ACR, 1987) and 28 controls. For Class I and II HLA typing, we adopted the PCR-SSP, and statistical significances were evaluated by Chi-Square.
HLA-DR4 is present in 76.7% of patients, with an allele frequency of 45%, while only 21% of control subjects presented it. The chi-square confirms that HLA-DR4 and RA variables are highly bound (X2 = 11.38, P = 0.00074).
There is increased frequency of HLA-DR4 and HLA-DR14. The results are similar to those found in other studies. But it would be desirable to increase the sample size in order to find a greater number of genetic profiles and alleles involved.
La artritis reumatoide es una enfermedad sistémica autoinmune, crónica, que afecta principalmente las articulaciones que tienen movimiento. La enfermedad es mucho más frecuente en mujeres y su prevalencia en la población latinoamericana es cercana al 0,5%. La existencia de agregación familiar (ls= 2-17) indica su carácter hereditario. Sin embargo, la herencia de la artritis reumatoide es poligénica y no sigue un patrón mendeliano. La importancia de encontrar factores genéticos asociados con la artritis reumatoide radica en la contribución a la comprensión de los mecanismos patogénicos de la enfermedad, su posible aplicación clínica como marcadores de riesgo, diagnóstico, pronóstico, e incluso, blanco terapéutico. Mapeos genéticos llevados a cabo en diversas poblaciones en busca de loci y genes candidatos han identificado la región HLA como aquella con mayor evidencia de ligamento. Sin embargo, su fracción etiológica corresponde sólo a un tercio de la susceptibilidad genética de la enfermedad. Esto indica que genes diferentes al HLA también están implicados en la susceptibilidad a desarrollar artritis reumatoide. En Latinoamérica, los alelos HLA-RB1*0404 y TNF -308A han sido asociados de manera uniforme con la artritis reumatoide. En el presente artículo se revisan los factores genéticos de la artritis reumatoide en el marco de una aproximación lógica y ordenada establecida por la epidemiología genética, y se ofrecen algunas recomendaciones para futuros estudios en poblaciones latinoamericanas.
To examine the contribution of tumor necrosis factor alpha (TNF) microsatellite (a to e) polymorphism to the genetic risk of developing rheumatoid arthritis (RA) in a northwestern Colombian population.
This was an association study in which 108 RA patients and 222 matched individuals were enrolled. HLA-DRB1 and DQB1 polymorphisms were evaluated to examine for linkage disequilibrium between these loci and TNF micro- satellites. Genotyping was performed using denaturing polyacrylamide gels and polymerase chain reaction-sequence techniques.
By unconditional logistic regression analysis, the TNFa6 allele (OR=2.37, 95%CI 1.07-5.24) and the TNFb4 allele (OR=3.01, 95%CI 1.07-9.00) were observed to be associated with disease. These associations were independent of HLA-DR and HLA-DQ since linkage disequilibrium between HLA class II and TNF microsatellites was not observed. In addition, patients with the TNFa8 allele had a five times greater risk of developing extra-articular manifestations as compared to patients without this allele (OR=5.07, 95%CI 1.14-22.52), regardless of age and the duration of disease. Haplotype analysis disclosed a protective effect for TNFa7/b7/c1/d4/e3/-308G/-238G.
These results confirm that the TNF locus exerts a primary influence on both susceptibility to and the severity of RA.
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