RESUMEN
PURPOSE: Chemokines are a group of cytokines that guide immune cell migration. We studied plasma levels of inflammatory chemokines in patients with polypoidal choroidal vasculopathy (PCV) and compared with healthy age-matched control individuals. METHODS: This was a clinic-based prospective case-control study of participants (n = 60) with either PCV (n = 26) or age-matched healthy controls (n = 34). We sampled fresh venous blood and isolated plasma for analysis. We used U-PLEX Human Assays to quantify concentrations of the inflammatory chemokines MCP-1/CCL2, RANTES/CCL5, eotaxin/CCL11, IP-10/CXCL10 and fractalkine/CX3CL1. RESULTS: Plasma levels of fractalkine was significantly higher in patients with PCV when compared to healthy controls (mean ± SD: 7291 ± 2461 pg/ml versus 5879 ± 2001 pg/ml; p = 0.021). Plasma levels of MCP-1 (p = 0.846), RANTES (p = 0.288), eotaxin (p = 0.496) and IP-10 (p = 0.352) did not differ significantly between the groups. To evaluate possible biomarker quality of fractalkine, we used a ROC analysis and found a positive but weak discriminatory ability (AUC = 0.68). CONCLUSION: Patients with PCV have a higher plasma level of fractalkine. Although the differences do not possess strong biomarker qualities, they inform on disease processes of a poorly understood disease and suggest that the fractalkine-CX3CR1 axis may be involved. As this study did not investigate local chemokine concentrations, we are unable to confirm or disprove any local chorioretinal interaction, and our findings should be interpreted with such caution.
Asunto(s)
Quimiocinas/sangre , Enfermedades de la Coroides/sangre , Coroides/irrigación sanguínea , Inflamación/sangre , Pólipos/sangre , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedades de la Coroides/diagnóstico , Femenino , Angiografía con Fluoresceína/métodos , Fondo de Ojo , Humanos , Inflamación/diagnóstico , Masculino , Oftalmoscopía/métodos , Pólipos/diagnóstico , Estudios Prospectivos , Microscopía con Lámpara de Hendidura , Tomografía de Coherencia Óptica/métodosRESUMEN
BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) may be complicated by primary sclerosing cholangitis (PSC). We aimed to assess the characteristics of Danish PSC-IBD patients and to compare their prognosis with IBD patients without PSC. METHODS: A retrospective nationwide population-based cohort of 257 PSC-IBD patients was assessed through Danish national registries and manual scrutiny of patient files. RESULTS: For all PSC-IBD patients diagnosed after 1976 (n = 222) and 8231 IBD controls (ie, without PSC), the cumulative probability of resective surgery, liver transplantation, cancer, and survival from 1977 through 2011 was estimated and compared by log-rank test and Cox regression. PSC-IBD patients primarily had ulcerative colitis (UC) (72%), were diagnosed in young adulthood (median age at IBD diagnosis, 23 years), and 9% were smokers. Among PSC-UC patients 78% had pancolitis at diagnosis. Among patients with PSC and Crohn's disease (CD) 91% had colonic involvement. The PSC-IBD patients had a significantly higher probability of receiving resective surgery (HR; 2.13, 95% CI: 1.50-3.03); of developing colorectal cancer (CRC) (HR; 21.4, 95% CI: 9.6-47.6), of cholangiocarcinoma (HR; 190, 95% CI: 54.8-660), and of dying (HR; 4.39, 95% CI: 3.22-6.00) as compared to non-PSC-IBD controls. The 25-year cumulative risk of liver transplantation was high (53%). CONCLUSIONS: This unselected population-based study shows that PSC-IBD patients not only have an extensive phenotype of IBD, they are also treated more intensively than other patients with IBD. However, the prognosis remains poor and without any apparent improvement over calendar time.
Asunto(s)
Colangitis Esclerosante/complicaciones , Neoplasias Colorrectales/complicaciones , Enfermedades Inflamatorias del Intestino/complicaciones , Adolescente , Adulto , Anciano , Niño , Preescolar , Colangitis Esclerosante/mortalidad , Colangitis Esclerosante/cirugía , Colectomía , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Dinamarca/epidemiología , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/mortalidad , Enfermedades Inflamatorias del Intestino/cirugía , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
In the last two decades, natural killer T (NKT) cells have emerged as an important factor in preventing type 1 diabetes (T1D) when investigated in the experimental non-obese diabetic (NOD) mouse model. So far, investigations have largely focused on type 1 NKT cells with invariant T-cell receptors, whereas the role of type 2 NKT cells with diverse T-cell receptors is less well understood. However, there have been several findings which indicate that in fact type 2 NKT cells may regulate the progression of type 1 diabetes in NOD mice, including a fraction of these cells which recognize ß-cell-enriched sulfatide. Therefore, the focus for this review is to present the current evidence of the effect of type 2 NKT cells on the development of T1D. In general, there is still uncertainty surrounding the mechanism of activation and function of NKT cells. Here, we present two models of the effector mechanisms, respectively, Th1/Th2 polarization and the induction of tolerogenic dendritic cells (DC). In conclusion, this review points to the importance of immunoregulation by type 2 NKT cells in preventing the development of T1D and highlights the induction of tolerogenic DC as a likely mechanism. The possible therapeutic role of type 1 and type 2 NKT cells are evaluated and future experiments concerning type 2 NKT cells and T1D are proposed.