RESUMO
BACKGROUND: Polymorphisms in several genes (NOD2, MDR1, SLC22A4) have been associated with susceptibility to Crohn's disease. Identification of the remaining Crohn's susceptibility genes is essential for the development of disease-specific targets for immunotherapy. Using gene expression analysis, we identified a differentially expressed gene on 5q33, the colony stimulating factor 1 receptor (CSF1R) gene, and hypothesized that it is a Crohn's susceptibility gene. The CSF1R gene is involved in monocyte to macrophage differentiation and in innate immunity. METHODS: Patients provided informed consent prior to entry into the study as approved by the Institutional Review Board at LSU Health Sciences Center. We performed forward and reverse sequencing of genomic DNA from 111 unrelated patients with Crohn's disease and 108 controls. We also stained paraffin-embedded, ileal and colonic tissue sections from patients with Crohn's disease and controls with a polyclonal antibody raised against the human CSF1R protein. RESULTS: A single nucleotide polymorphism (A2033T) near a Runx1 binding site in the eleventh intron of the colony stimulating factor 1 receptor was identified. The T allele of this single nucleotide polymorphism occurred in 27% of patients with Crohn's disease but in only 13% of controls (X2 = 6.74, p < 0.01, odds ratio (O.R.) = 2.49, 1.23 < O.R. < 5.01). Using immunohistochemistry, positive staining with a polyclonal antibody to CSF1R was observed in the superficial epithelium of ileal and colonic tissue sections. CONCLUSIONS: We conclude that the colony stimulating factor receptor 1 gene may be a susceptibility gene for Crohn's disease.
RESUMO
La enteropatía perdedora de proteínas es una de las manifestaciones gastrointestinales del lupus eritematoso sistémico (LES); se caracteriza por hipoalbuminemia sérica con o sin edema y algunos síntomas digestivos. Se informa el caso de una niña de 13 años quien presentó dolor abdominal, diarrea, edema generalizado e hipoalbuminemia. Se hizó el diagnóstico de enteropatía perdedora de proteínas con base en el marcado incremento de la depuración de alfa-1 antitripsina en las heces de 24 horas; la paciente tenía más de los cuatro criterios establecidos por el Colegio Americano de Reumatología para el diagnóstico de LES. Hasta la fecha se han descrito aproximadamente 22 casos de enteropatía perdedora de proteínas asociada al LES, pero únicamente tres en el lupus pediátrico. Sugerimos que se debe sospechar esta afección en todo individuo con LES que presente edema o hipoalbuminemia no nefrogénicos.
