Association of homocysteine and inflammatory-related molecules in sickle cell anemia.

OBJECTIVE: Investigate the role of homocysteine (Hcy), Th17-related cytokines, and adhesion molecules in the inflammatory state seen in the sickle cell anemia (SCA). METHODS: We studied the Hcy, interleukin (IL)-17, and transforming growth factor ß (TGF-ß) cytokine levels of 62 SCA patients, as well as the expression levels of inflammatory and endothelial activation markers. RESULTS: We found significant associations between Hcy levels and increased expression of IL-17 and TGF-ß among SCA patients, and a positive significant correlation between Hcy and soluble vascular cellular adhesion molecules (sVCAM). SCA individuals had raised IL-17 levels when compared with controls. DISCUSSION: These results suggest a possible role of Hyc in the induction of TGF-ß and IL-17. Other authors proposed that Hcy may contribute to the initiation and progression of vascular disease by monocyte activation, resulting in the secretion of cytokines that amplify the inflammatory response. The role of Hcy in cytokine production and oxidative stress in the endothelium may explain the increase of sVCAM expression and, the vascular activation currently described among the SCA individuals with the highest Hcy serum levels. The chronic inflammation was observed in hyperhomocysteinemic mice, with an increased expression of VCAM-1 and plasma levels of tumor necrosis factor-alpha, showing an association of this inflammatory molecule and vascular changes. CONCLUSION: Our findings suggest that the increased levels of IL-17,Hcy and sVCAM contributes contributes to the vascular inflammation and activation presented by SCA patients, which probably have an important role in vaso-occlusion. On the basis of the presented data, IL-17 and Hcy might be considered as important components in the pathogenesis of SCA.

Valor de la determinación de los niveles de moléculas de adhesión solublesen el diagnóstico de la vasculitis reumatoidea / Value of the determination of levels soluble adhesion molecules in the diagnosis of rheumatoid vasculitis

La Vasculitis Reumatoidea (VR) es una complicación severa de laArtritis Reumatoidea (AR). Varios estudios demuestran que las moléculasde adhesión soluble serían indicadores de activación endotelial y se asociarían a daño vascular. Objetivo: Medir los niveles séricos de moléculas de adhesión solubles en pacientes con VR y evaluar la utilidad de las mismas para elmonitoreo de la respuesta terapéutica.Material y métodos: Se incluyeron en forma consecutiva pacientes con AR según criterios ACR’87 y diagnóstico VR. Por cada paciente con VR, se evaluaron 2 pacientes con AR sin vasculitis apareados por edad, sexo y tiempo de evolución de la enfermedad. Se consignaron datos demográficos, hábitos tóxicos, enfermedades comórbidas, parámetros de laboratorio, datos relacionados a la AR, en el momento previo al proceso vasculítico, en el período activo y 6 meses posterior al inicio del tratamiento específico para vasculitis. Las moléculas de adhesión VCAM-1 y E-selectina fueron medidaspor método de ELISA, en ambos grupos basalmente y luego de 6 meses de iniciado el tratamiento. Resultados: Los pacientes con VR (n = 10) tenían una edad mediana de 51 años (RIC 42,2-55,2) y un tiempo mediano de evolución de la enfermedad de 84 meses (RIC 69-180). El 80% era de sexo femenino. Los pacientes con AR sin VR (n = 20) tenían característicasdemográficas y tiempo de evolución de la enfermedad comparables. El 80% de los pacientes con VR presentaban compromiso cutáneo. El 100% tenía compromiso neurológico. Todos los pacientes recibieron tratamiento con esteroides, 9 pulsos de ciclofosfamida y1 azatioprina. Los niveles de VCAM-1 fueron significativamente mayores en pacientes con VR vs. controles (765 μg/ml vs. 595 μg/ml,p = 0,033). Los valores de E-selectina fueron mayores en vasculitis vs. controles (49,25 μg/ml vs. 40,3 μg/ml), pero esta diferencia noalcanzó significancia estadística. Los niveles VCAM-1 también disminuyeronen forma significativa...

Rheumatoid vasculitis (RV) is a severe complication in patients with RA. Some studies demonstrated that the soluble adhesion molecules are associated with endothelial activation and vascular damage. Objective:To measure serum levels of soluble adhesion moleculesin RA patients with RV and to evaluate their utility for monitoring thetherapeutic response. Material and methods:Consecutive patients with RA (ACR’87) and RV were included. For each patient with RV, 2 patients with RA and without RV matched by age, sex and disease duration were used as controls. Demographical data, toxic habits, comorbidities, laboratory, RA characteristics were registered previously vasculitis, in the active period and 6 months after the beginning of the specific vasculitis treatment. The adhesion molecules VCAM-1 and E-selectin were measured by ELISA, in both groups, basally and 6 months afterof the therapy beginning. Results: RV patients (n = 10) median age 51 years (IQR 42.2-55.2) and median disease duration 84 months (IQR 69-180) and80% female sex. RA patients without RV (n = 20) had comparabledemographical and disease duration. 80% RV patients had skin involvement. 100% had neurological involvement. All the patients received steroids treatment, 9 IV cyclophosphamide and 1 azathioprine. VCAM-1 levels were significantly greater in RV patients vs.controls (765 μg/ml vs. 595 μg/ml, p = 0.033). E-selectin levels were also greater in vasculitis vs. controls (49.25 μg/ml vs. 40.3 μg/ml), but this difference did not reach statistical significance. VCAM-1 levels significantly decreased after 6 months of treatment, 765 μg/ml (592.5-975) vs. 555 μg/ml (455-685), p = 0.01. We did not observe difference in E-selectin levels.Conclusion: VCAM-1 levels are increased in RV patients versus RA patients without RV and these soluble adhesion molecules decreased after treatment. The VCAM-1 measurement could be a useful vascular inflammation indicator in RV and would allow to monitoring treatment.

Valor de la determinación de los niveles de moléculas de adhesión solublesen el diagnóstico de la vasculitis reumatoidea / Value of the determination of levels soluble adhesion molecules in the diagnosis of rheumatoid vasculitis

La Vasculitis Reumatoidea (VR) es una complicación severa de laArtritis Reumatoidea (AR). Varios estudios demuestran que las moléculasde adhesión soluble serían indicadores de activación endotelial y se asociarían a daño vascular. Objetivo: Medir los niveles séricos de moléculas de adhesión solubles en pacientes con VR y evaluar la utilidad de las mismas para elmonitoreo de la respuesta terapéutica.Material y métodos: Se incluyeron en forma consecutiva pacientes con AR según criterios ACR87 y diagnóstico VR. Por cada paciente con VR, se evaluaron 2 pacientes con AR sin vasculitis apareados por edad, sexo y tiempo de evolución de la enfermedad. Se consignaron datos demográficos, hábitos tóxicos, enfermedades comórbidas, parámetros de laboratorio, datos relacionados a la AR, en el momento previo al proceso vasculítico, en el período activo y 6 meses posterior al inicio del tratamiento específico para vasculitis. Las moléculas de adhesión VCAM-1 y E-selectina fueron medidaspor método de ELISA, en ambos grupos basalmente y luego de 6 meses de iniciado el tratamiento. Resultados: Los pacientes con VR (n = 10) tenían una edad mediana de 51 años (RIC 42,2-55,2) y un tiempo mediano de evolución de la enfermedad de 84 meses (RIC 69-180). El 80% era de sexo femenino. Los pacientes con AR sin VR (n = 20) tenían característicasdemográficas y tiempo de evolución de la enfermedad comparables. El 80% de los pacientes con VR presentaban compromiso cutáneo. El 100% tenía compromiso neurológico. Todos los pacientes recibieron tratamiento con esteroides, 9 pulsos de ciclofosfamida y1 azatioprina. Los niveles de VCAM-1 fueron significativamente mayores en pacientes con VR vs. controles (765 μg/ml vs. 595 μg/ml,p = 0,033). Los valores de E-selectina fueron mayores en vasculitis vs. controles (49,25 μg/ml vs. 40,3 μg/ml), pero esta diferencia noalcanzó significancia estadística. Los niveles VCAM-1 también disminuyeronen forma significativa...(AU)

Rheumatoid vasculitis (RV) is a severe complication in patients with RA. Some studies demonstrated that the soluble adhesion molecules are associated with endothelial activation and vascular damage. Objective:To measure serum levels of soluble adhesion moleculesin RA patients with RV and to evaluate their utility for monitoring thetherapeutic response. Material and methods:Consecutive patients with RA (ACR87) and RV were included. For each patient with RV, 2 patients with RA and without RV matched by age, sex and disease duration were used as controls. Demographical data, toxic habits, comorbidities, laboratory, RA characteristics were registered previously vasculitis, in the active period and 6 months after the beginning of the specific vasculitis treatment. The adhesion molecules VCAM-1 and E-selectin were measured by ELISA, in both groups, basally and 6 months afterof the therapy beginning. Results: RV patients (n = 10) median age 51 years (IQR 42.2-55.2) and median disease duration 84 months (IQR 69-180) and80% female sex. RA patients without RV (n = 20) had comparabledemographical and disease duration. 80% RV patients had skin involvement. 100% had neurological involvement. All the patients received steroids treatment, 9 IV cyclophosphamide and 1 azathioprine. VCAM-1 levels were significantly greater in RV patients vs.controls (765 μg/ml vs. 595 μg/ml, p = 0.033). E-selectin levels were also greater in vasculitis vs. controls (49.25 μg/ml vs. 40.3 μg/ml), but this difference did not reach statistical significance. VCAM-1 levels significantly decreased after 6 months of treatment, 765 μg/ml (592.5-975) vs. 555 μg/ml (455-685), p = 0.01. We did not observe difference in E-selectin levels.Conclusion: VCAM-1 levels are increased in RV patients versus RA patients without RV and these soluble adhesion molecules decreased after treatment. The VCAM-1 measurement could be a useful vascular inflammation indicator in RV and would allow to monitoring treatment.(AU)