Negative association between 25-hydroxyvitamin D and inflammatory markers in rheumatologic diseases / Asociación negativa entre 25-hidroxi vitamina D y los marcadores inflamatorios en enfermedades reumatológicas

Objective: The main purpose of this study was to evaluate serum 25-hydroxyvitamin D (25OHD) levels and its association with in"ammatory markers in patients with rheumatologic diseases (RD). Methods: A cross-sectional study in 154 women with RD (rheumatoid arthritis, spondyloarthritis and other connective tissue diseases) and 112 healthy individuals as a control group (CG) was carried out. Results: No differences in serum and urine calcium, serum phosphate, and urinary deoxypyridinoline were found. RD group had lower 25OHD and higher PTH compared to CG. RD group had higher C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) compared to CG. The overall mean level of 25OHD (ng/ml) was 26.3±12.0 in the CG and 19.4±6.8 in the RD group (p<0.0001). Moreover, CG had lower percentage of individuals with 25OHD de!ciency compared to RD (29.9% vs 53.2%). The femoral neck BMD was signi!cantly lower in postmenopausal RD women compared to CG. 25OHD levels signi!cantly correlated with ESR and CRP as in"ammatory markers. Age, BMI, presence of RD, and CRP were signi!cantly and negatively associated with 25OHD levels through linear regression analysis. According to univariate logistic regression analysis for 25OHD deficiency (<20 ng/ml), a significant and negative association with BMI, presence of RD, ESR and CRP were found. Conclusion: Patients with RD had lower 25OHD levels than controls and the presence of a RD increases by 2.66 the risk of vitamin D de!ciency. In addition, 25OHD has a negative correlation with ESR and CRP as in"ammatory markers. (AU)

Objetivo El objetivo principal de este estudio fue evaluar los niveles séricos de 25-hidroxivitamina D (25OHD) y su asociación con marcadores inflamatorios en enfermedades reumatológicas. Materiales y métodos: Se realizó un estudio transversal en 154 mujeres con enfermedades reumatológicas (artritis reumatoide, espondiloartritis y otras enfermedades del tejido conectivo) y 112 individuos sanos como grupo control (GC). Resultados: No se encontraron diferencias en el calcio sérico y urinario, el fosfato sérico y la desoxipiridinolina urinaria entre el GC y los sujetos con enfermedades reumatológicas. El grupo de pacientes con enfermedades reumatológicas tenía 25OHD más bajo y PTH más alto en comparación con el GC. Asimismo, el grupo de individuos con enfermedades reumatológicas tenía proteína C reactiva (PCR) y velocidad de eritrosedimentación (VES) más altas en comparación con el GC. El nivel de 25OHD (ng/ml) fue 26,3±12,0 en el GC y 19,4±6,8 en el grupo con enfermedades reumatológicas (p<0,0001). Además, el GC presentó un porcentaje menor de deficiencia de 25OHD en comparación con el grupo con enfermedades reumatológicas (29,9% vs 53,2%). La DMO del cuello femoral fue significativamente menor en las mujeres posmenopáusicas con enfermedades reumatológicas en comparación con el GC. La 25OHD correlacionó significativamente con la VES y la PCR como marcadores inflamatorios. El análisis de regresión lineal mostró que la edad, el IMC, la presencia de una enfermedad reumatológica y la PCR se asociaron significativa y negativamente con los niveles de 25OHD. Mientras que el análisis de regresión logística univariada mostró que la deficiencia de 25OHD (<20 ng/ml), se asoció significativa y negativamente con el IMC, la presencia de una enfermedad reumatológica, la VES y los niveles de PCR. Conclusiones: Los pacientes con enfermedades reumatológicas tenían niveles de 25OHD más bajos que los controles y la presencia de una enfermedad reumatológica aumenta en 2.66 el riesgo de deficiencia de vitamina D. Además, la 25OHD mostró correlación negativa con la VES y la PCR como marcadores inflamatorios. (AU)

Five year retrospective study of mortality in systemic inflammatory rheumatologic disorders

Background: Inflammatory systemic rheumatologic disorders are responsible for significant morbidity and premature deaths. The present study was done to assess causes of mortality in these patients.Methods: In the retrospective study, the death records of patients with inflammatory rheumatologic illnesses from January 2012 to January 2017 were studied. The demographic details, disease activity, organ involvement, treatment received and evidence of infection were noted.Results: 50 records were analyzed (25 systemic lupus erythematosus (SLE), 13 rheumatoid arthritis (RA), four immune myositis, three systemic sclerosis (SS), two takayasu’s arteritis (TA), two ankylosing spondylitis (AS) and one granulomatosis with polyangiitis (GPA)). The me an age of death was 39.94 years. Sixteen patients had disease related organ damage, 17 had active disease. Infection was present in 31 patients (gram negative organisms most commonly isolated), being the major contributor of mortality. Only two patients succumbed to acute coronary syndrome.Conclusions: Infection, disease activity and organ damage due to the disease are the major contributors to of death in hospitalized patients with inflammatory rheumatological disorders.

Estrés, psiconeuroendocrinoinmunología y enfermedades reumatológicas. Actualización del tema / Stress, Psychoneuroendocrinoimmunology and rheumatological diseases. Actualization of this topic

El estrés se define como el estado de alarma de los organismos ante diversos desafíos. La Psiconeuroendocrinoinmunología es una ciencia que integra la psiquis, el sistema nervioso, endocrino e inmune; y estudia las múltiples y complejas interrelaciones entre ellos lo cual permite tratar de manera integral el proceso salud-enfermedad. La alteración del equilibrio entre la psiquis y los sistemas mencionados puede ocasionar daños al organismo como es el caso de algunas enfermedades reumatológicas(AU)

Stress is defined as the state of alarm of living beings in case of various challenges. Psycho-neuro-endocrine-immunology is a science that integrates the psyche with the nervous, endocrine and immune systems. It studies the multiple and complex interrelations among them, which allows us to deal comprehensively with the health-disease process. The alteration if the balance between the psyche and the aforementioned systems can cause damage to the organism, as in the case of some rheumatologic diseases(AU)

Influência dos polimorfismos genéticos (IL10/CXCL8/CXCR2/ NF?B) na susceptibilidade das doenças reumatológicas autoimunes / Influence of genetic polymorphisms (IL-10/CXCL8/CXCR2/ NF?B) on the susceptibility of autoimmune rheumatic diseases

As doenças reumatológicas autoimunes, na maioria das vezes, possuem uma via genética comum para a autoimunidade. Vários genes foram associados com as doenças reumatológicas, para tanto iremos analisar somente alguns genes nos quais há várias evidências da existência de associação com risco ou proteção de doença autoimune. O fator de transcrição nuclear kappa B (NF-kappa B), o qual regula as respostas imunes e inflamatórias, está associado com esclerose sistêmica (ES), artrite reumatoide (AR) e lúpus eritematoso sistêmico (LES), assim como os genes CXCR2 e CXCL8. Já a interleucina 10 (IL-10), que é uma citocina anti-inflamatória, está associada com quase todas as doenças reumatológicas. Neste artigo, revisamos os potenciais papéis desses genes no sistema imunológico e em diversas doenças reumatológicas. Com relação à IL-10, diversos estudos foram realizados, porém em sua maioria contraditórios - alguns encontraram ausência de associação e outros encontraram associação em diferentes polimorfismos do genes. Já em relação ao NF-kappa B, somente foi estudado em AR e LES, e não foram observadas análises significativas relevantes. Os polimorfismos genéticos do gene CXCR2 foram associados com ES, mas não estão associados com AR e LES. Já os polimorfismos genéticos do gene CXCL8 não estão associados com ES, mas estão associados com AR.

The autoimmune rheumatologic disorders mostly have a common genetic path to the autoimmunity. Several genes have been associated with rheumatologic disorders; therefore, we are analyzing just the ones in those containing several evidences of the existence of association with the risk or protection from autoimmune disorder. The nuclear factor kappa beta (NF-kappa B), which regulates the autoimmune and anti-inflammatory responses, is associated with systemic sclerosis (SS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), just as the CXCR2 e CXCL8 genes. On the other hand, the interleukin-10 (IL-10), which is an anti-inflammatory cytokine, is associated with almost all rheumatologic disorders. In this article, we are reviewing the potential roles of these genes in the immune system and in several rheumatologic disorders. In relation to IL-10, several studies have been carried out, but most of them are controversial - some detected the absence of association, and others found association in different genetic polymorphisms. Conversely, in relation to NF-kappa B, it was studied just in RA and SLE, and no relevant significant analyses were observed. The genetic polymorphisms of the CXCR2 gene were associated with SS, but not with RA e SLE. On the other side, the genetic polymorphisms of the CXCL8 gene are not associated with SS, but with RA.

Anticoncepción hormonal en mujeres jóvenes con enfermedades reumatológicas / Hormonal contraception in young women with rheumatic diseases

Antecedentes: Las enfermedades reumatológicas (ER) se presentan con mayor frecuencia en mujeres en edad fértil. Es durante este período que muchas mujeres consultan por trastornos de los flujos rojos, dismenorrea y prevención del embarazo. Objetivo: Realizar una puesta al día del uso de anticoncepción hormonal (AH) en mujeres jóvenes con ER, especialmente en las portadoras de lupus eritematoso sistémico (LES) y artritis reumatoide (AR). Método: Se revisó la literatura en Pubmed para los términos AH en ER, con especial énfasis en guías clínicas y ensayos clínicos aleatorizados. Resultados: El uso de AH en pacientes con LES inactivo o con actividad leve no ha mostrado un empeoramiento de la enfermedad. Tampoco existe evidencia categórica que demuestre un mayor riesgo trombótico en aquellas con anticuerpos antifosfolípidos negativos, para las cuales se recomienda el uso de cualquier tipo de AH. En pacientes con AR no se ha demostrado asociación del uso de AH y aumento de la actividad de la enfermedad. Además la interacción farmacológica entre AH y medicamentos reumatológicos es mínima. Existe escasa evidencia del uso de AH en mujeres menores de 18 años con ER. Conclusión: Basado en la evidencia disponible las pacientes con ER con anticuerpos antifosfolípidos negativos podrán utilizar AH según los criterios de la OMS, lo que abre las puertas a mayores alternativas terapéuticas y prevención de embarazo para estas adolescentes y mujeres jóvenes con ER.

Background: Rheumatologic diseases (RD) are most common in women of childbearing age. It is during this period that many women consult for menstrual disorders, dysmenorrhea and pregnancy prevention. Objective: To update the use of hormonal contraception (HC) in young women with RD. Method: Literature was reviewed in PubMed for HC and RD terms, with special emphasis on clinical guidelines and randomized clinical trials. Results: The use of HC in patients with inactive or mild activity systemic lupus erythematosus has not shown a worsening of the disease. Also, there is no evidence demonstrating greater thrombotic risk in those with negative antiphospholipid antibodies, for which the use of any type of HC is recommended. In patients with rheumatoid arthritis an association between use of HC and increases disease activity has not been demonstrated. In addition, there is minimal drug interaction between HC and rheumatologic drugs. There is little evidence of the use of HC in women less than 18 years with RD. Conclusion: Based on the available evidence the patients with RD and negative antiphospholipid antibodies could use HC according to WHO criteria, which leads to greater therapeutic alternatives and pregnancy prevention for these adolescents and young women with RD.

O papel do gene e da molécula HLA-G na expressão clínica das doenças reumatológicas / The role of the HLA-G gene and molecule on the clinical expression of rheumatologic diseases

O antígeno leucocitário humano G (HLA-G) é uma molécula não clássica de complexo principal de histocompatibilidade (MHC) de classe I, caracterizada por baixo polimorfismo em sua região codificadora, um padrão de distribuição tecidual limitado em condições fisiológicas e expressão por meio de isoformas solúveis e acopladas à superfície de membranas por meio de splicing alternativo. O HLA-G é bastante conhecido por estar envolvido na indução e na manutenção da tolerância entre o sistema imunológico materno e o feto semialogênico ao nível da interface fetoplacentária. Além disso, diversos estudos apontam para um papel imunorregulatório mais amplo dessa molécula. Neste contexto, a expressão de HLA-G em doenças inflamatórias e reumatológicas é uma área relativamente recente de pesquisa. Os primeiros estudos descreveram a expressão de HLA-G em várias miopatias inflamatórias, dermatite atópica e psoríase cutânea. Com base nos achados de que o HLA-G poderia desviar respostas T helper para o tipo Th2, foi levantada a hipótese de que o HLA-G seria uma molécula protetora nas respostas inflamatórias. Neste artigo, revisamos os potenciais papéis da molécula HLA-G no sistema imunológico e em diversas doenças reumatológicas, tais como lúpus eritematoso sistêmico, artrite reumatoide, esclerose sistêmica e outras.

Human leukocyte antigen G (HLA-G) is a non-classic class I major histocompatibility complex (MHC) molecule characterized by low polymorphism in its coding region, a limited tissue distribution pattern in physiologic conditions, and expression through soluble isoforms and isoforms bound to surface membranes through alternative splicing. HLA-G is fairly known since it is involved in induction and maintenance of tolerance between the maternal immunologic system and the semi-allogeneic fetus at the level of the fetal-placental interface. Besides, several studies have indicated a wider immunoregulatory role of this molecule. In this context, the expression of HLA-G in inflammatory and rheumatologic diseases is a relatively recent research area. The first studies described the expression of HLA-G in several inflammatory myopathies, atopic dermatitis, and cutaneous psoriasis. Based on the findings that HLA-G could divert T helper responses to the Th2 type, it was hypothesized that HLA-G would be a protective molecule in inflammatory responses. In this article, we review the potential roles of the HLA-G molecule in the immune system and in several rheumatologic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and others.