Utility of cytokines CXCL4, CXCL8 and GDF15 as biomarkers in systemic sclerosis

Background and objectives: Systemic sclerosis (SSc) is an autoinmune disease that can affect several organs and its mortality is fundamentally related to its pulmonary involvement. There are some cytokines with high serum levels of patients with SSc. Our goal is to determine the role of CXCL4, CXCL8 and GDF15 in the physiopathology of SSc and whether they can be considered organic damage biomarkers.Patients and methodsObservational case–control study of SSc patients (ACR/EULAR 2013 criteria). Demographic, clinical, analytical, activity, severity, health perception, and disability variables were collected. Moreover, Videocapillaroscopy, Echocardiography and Respiratory Function Test were made. Serum levels of CXCL4, CXCL8 and GDF15 were measured both in SSc patients and in healthy controls.ResultsA total of 42 patients were included (95.4% women), with an average age of 59.2 years and a median of 4 years from diagnosis. We also included 42 healthy controls. We found significantly higher levels of GDF15 in SSc patients than in controls (p<0.001), but no higher CXCL4 or CXCL8 levels. GDF15 was associated with Diffuse SSc, pulmonary arterial hypertension, interstitial lung disease, less forced vital capacity, high titles of antiScl70, disease activity, and dilated loops in capillaroscopy. CXCL4 levels were associated to a higher Rodnan punctuation, while CXCL8 was associated to C4 fraction consumption and tortuosities in capillaroscopy. (AU)

Antecedentes y objetivos: La esclerosis sistémica (ES) es una enfermedad autoinmunitaria que afecta a diferentes órganos y cuya mortalidad se relaciona fundamentalmente con su afectación pulmonar. Los pacientes con ES presentan niveles séricos elevados de algunas citocinas. Nuestro objetivo es determinar el papel de CXCL4, CXCL8 y GDF15 en la fisiopatología de la ES, y si pueden considerarse biomarcadores de daño orgánico.Pacientes y métodosEstudio observacional de casos-controles, con pacientes afectados de ES (criterios ACR/EULAR 2013) y controles sanos. Se determinaron los niveles séricos de CXCL4, CXCL8 y GDF15 en ambos grupos, y se registraron variables demográficas, clínicas, analíticas, de actividad, gravedad, percepción de salud y discapacidad de pacientes con ES, a quienes, además, se les realizó videocapilaroscopia, ecocardiograma y espirometría.ResultadosSe incluyeron 42 pacientes (95,4% mujeres), con una edad media de 59,2 años y una mediana de 4 años desde el diagnóstico, con 42 controles sanos. Se hallaron niveles significativamente mayores de GDF15 en pacientes con ES que en controles (p<0,001), pero no de CXCL4 ni CXCL8. GDF15 se asoció a ES difusa, hipertensión pulmonar, enfermedad pulmonar intersticial, menor capacidad vital forzada, títulos altos de anti-Scl70, actividad de ES y dilataciones capilares. Asimismo, los niveles de CXCL4 se asociaron a mayor afectación cutánea (Rodnan), mientras que CXCL8 se asoció a consumo de la fracción C4 del complemento y tortuosidades en la capilaroscopia. (AU)

Utility of cytokines CXCL4, CXCL8 and GDF15 as biomarkers in systemic sclerosis.

BACKGROUND AND OBJECTIVES: Systemic sclerosis (SSc) is an autoinmune disease that can affect several organs and its mortality is fundamentally related to its pulmonary involvement. There are some cytokines with high serum levels of patients with SSc. Our goal is to determine the role of CXCL4, CXCL8 and GDF15 in the physiopathology of SSc and whether they can be considered organic damage biomarkers. PATIENTS AND METHODS: Observational case-control study of SSc patients (ACR/EULAR 2013 criteria). Demographic, clinical, analytical, activity, severity, health perception, and disability variables were collected. Moreover, Videocapillaroscopy, Echocardiography and Respiratory Function Test were made. Serum levels of CXCL4, CXCL8 and GDF15 were measured both in SSc patients and in healthy controls. RESULTS: A total of 42 patients were included (95.4% women), with an average age of 59.2 years and a median of 4 years from diagnosis. We also included 42 healthy controls. We found significantly higher levels of GDF15 in SSc patients than in controls (p<0.001), but no higher CXCL4 or CXCL8 levels. GDF15 was associated with Diffuse SSc, pulmonary arterial hypertension, interstitial lung disease, less forced vital capacity, high titles of antiScl70, disease activity, and dilated loops in capillaroscopy. CXCL4 levels were associated to a higher Rodnan punctuation, while CXCL8 was associated to C4 fraction consumption and tortuosities in capillaroscopy. CONCLUSIONS: GDF15 high levels were associated with diffuse SSc, lung impairment, disease activity and changes in capillaroscopy. Moreover, CXCL4 was only associated with skin impairment, while CXCL8 was not related to organic damage.

Características clínicas, tratamiento y complicaciones oculares de uveítis anterior asociada y no asociada a HLA-B27 / Clinical characteristics, treatment and ocular complications of HLA-B27-related anterior uveitis and HLA-B27-non related anterior uveitis

Introducción. La uveítis anterior es la forma más frecuente de inflamación intraocular. Las formas asociadas al antígeno HLA-B27 suponen entre un 18 y un 32% de los casos de uveítis anterior. Objetivos. Describir las características clínicas, la necesidad de tratamiento sistémico y la frecuencia y el tipo de complicaciones oculares de una cohorte de pacientes con uveítis anterior asociada a HLA-B27 y de una cohorte de pacientes con uveítis anterior no asociada a HLA-B27. Establecer si existen diferencias entre ambas cohortes. Material y métodos. Se realiza un estudio de cohortes retrospectivo descriptivo con componentes analíticos incluyendo a pacientes con uveítis anterior endógena no infecciosa asociada y no asociada a HLA-B27. Resultados. Se incluye un total de 162 pacientes, 58 con uveítis anterior asociada a HLAB27 (cohorte HLA-B27+) y 104 con uveítis anterior no asociada a HLA-B27 (cohorte HLA-B27-). No se aprecian diferencias estadísticamente significativas en las características clínicas de ambas cohortes a excepción de una mayor tendencia a la recurrencia en la cohorte HLA-B27+ y una mayor tendencia a la cronicidad en la cohorte HLA-B27-. Tampoco se aprecian diferencias en cuanto al uso de tratamiento sistémico ni al desarrollo de complicaciones oculares de forma global. Conclusiones. A diferencia de lo descrito con anterioridad, en este trabajo no encontramos un mayor predominio masculino en la cohorte de uveítis asociada a HLA-B27. Tampoco se aprecian diferencias en edad media, lateralidad, presencia de complicaciones ni frecuencia de uso de corticoides sistémicos (AU)

Introduction. Anterior uveitis is the most common type of intraocular inflammation. Those associated to HLA-B27 represent 18 to 32% of all anterior uveitis cases. Objectives. To describe clinical characteristics, systemic treatment need, and frequency and type of ocular complications in a cohort of patients diagnosed with HLAB27-related anterior uveitis and in a cohort of patients diagnosed with HLA-B27 non-related anterior uveitis. To establish if statistically significant differences between both cohorts exist. Material and methods. We performed a retrospective cohort study including patients with non infectious anterior uveitis related and not related to the antigen HLA-B27. Results. 162 patients were included, 58 diagnosed with HLA-B27-related anterior uveitis (cohort HLA-B27+1) and 104 diagnosed with HLA-B27- non related anterior uveitis (cohort HLA-B27-). No statistically significant differences were found regarding clinical characteristics between both cohorts with the exception of a higher frequency of recurrences in cohort HLA-B27+ and a higher frequency of chronic uveitis in cohort HLA-B27-. No differences were found regarding systemic treatment use nor development of ocular complications. Discussion. In contrast to previous studies, we neither found higher male gender predominance in the cohort of patients with HLA-B27-related anterior uveitis, Nor did we find differences regarding average age, laterality, development of complications nor use of systemic corticosteroids (AU)

Clinical characteristics, treatment and ocular complications of HLA-B27-related anterior uveitis and HLA-B27-non related anterior uveitis. / Características clínicas, tratamiento y complicaciones oculares de uveítis anterior asociada y no asociada a HLA-B27.

INTRODUCTION: Anterior uveitis is the most common type of intraocular inflammation. Those associated to HLA-B27 represent 18 to 32% of all anterior uveitis cases. OBJECTIVES: To describe clinical characteristics, systemic treatment need, and frequency and type of ocular complications in a cohort of patients diagnosed with HLAB27-related anterior uveitis and in a cohort of patients diagnosed with HLA-B27 non-related anterior uveitis. To establish if statistically significant differences between both cohorts exist. MATERIAL AND METHODS: We performed a retrospective cohort study including patients with non infectious anterior uveitis related and not related to the antigen HLA-B27. RESULTS: 162 patients were included, 58 diagnosed with HLA-B27-related anterior uveitis (cohort HLA-B27+1) and 104 diagnosed with HLA-B27- non related anterior uveitis (cohort HLA-B27-). No statistically significant differences were found regarding clinical characteristics between both cohorts with the exception of a higher frequency of recurrences in cohort HLA-B27+ and a higher frequency of chronic uveitis in cohort HLA-B27-. No differences were found regarding systemic treatment use nor development of ocular complications. DISCUSSION: In contrast to previous studies, we neither found higher male gender predominance in the cohort of patients with HLA-B27-related anterior uveitis, Nor did we find differences regarding average age, laterality, development of complications nor use of systemic corticosteroids.