ABSTRACT
A hallmark of celiac disease is autoantibodies to transglutaminase 2 (TG2). By visualizing TG2-specific antibodies by antigen staining of affected gut tissue, we identified TG2-specific plasma cells in the lamina propria as well as antibodies in the subepithelial layer, inside the epithelium, and at the brush border. The frequency of TG2-specific plasma cells were found not to correlate with serum antibody titers, suggesting that antibody production at other sites may contribute to serum antibody levels. Upon commencement of a gluten-free diet, the frequency of TG2-specific plasma cells in the lesion dropped dramatically within 6 months, yet some cells remained. The frequency of TG2-specific plasma cells in the celiac lesion is thus dynamically regulated in response to gluten exposure. Laser microdissection of plasma cell patches, followed by antibody gene sequencing, demonstrated that clonal cells were seeded in distinct areas of the mucosa. This was confirmed by immunoglobulin heavy chain repertoire analysis of plasma cells isolated from individual biopsies of two untreated patients, both for TG2-specific and non-TG2-specific cells. Our results shed new light on the processes underlying the B-cell response in celiac disease, and the approach of staining for antigen-specific antibodies should be applicable to other antibody-mediated diseases.
Subject(s)
Autoantibodies/genetics , Celiac Disease/immunology , GTP-Binding Proteins/immunology , Immunoglobulin Heavy Chains/genetics , Plasma Cells/immunology , Transglutaminases/immunology , Autoantibodies/biosynthesis , Biopsy , Celiac Disease/chemically induced , Celiac Disease/diet therapy , Celiac Disease/genetics , Cell Count , Diet, Gluten-Free , Duodenum/drug effects , Duodenum/immunology , Duodenum/pathology , GTP-Binding Proteins/genetics , Gene Expression Regulation/immunology , Glutens/adverse effects , Humans , Immunoglobulin Heavy Chains/biosynthesis , Intestinal Mucosa/drug effects , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Laser Capture Microdissection , Plasma Cells/drug effects , Plasma Cells/pathology , Protein Glutamine gamma Glutamyltransferase 2 , Sequence Analysis, DNA , Transglutaminases/geneticsABSTRACT
La papilomatosis pulmonar recurrente juvenil (PPRJ) es una enfermedad infecciosa que provoca el crecimiento de papilomas en la vía respiratoria en la que hasta en un 4% de los casos degeneran hacia un carcinoma de células escamosas. Presentamos el caso de una paciente de 17 años con PPRJ en la que se valora la utilidad de la 18F-FDG-PET/TC ante la sospecha de malignización de las lesiones papilomatosas. Las técnicas de imagen morfometabólicas, la TC y la PET/TC fueron sugestivas de malignidad. Sin embargo, esta no fue confirmada en el análisis anatomopatológico tras su resección. La FDG-PET/TC no parece una herramienta útil para la detección precoz de malignidad en la PPRJ, aunque sí aumenta la rentabilidad diagnóstica de la biopsia al identificar las lesiones más activas y, por lo tanto, con mayor posibilidad de ser malignas (AU)
Juvenile recurrent respiratory papillomatosis (JRRP) is an infectious disease caused by the growth of papillomas in the airway. Up to 4% of these cases degenerate into squamous cell carcinoma. We present the case of a 17-year-old female patient with JRRP in which the utility of 18F-FDG-PET/CT in the characterization of suspicious papillomatous lesions of malignancy is evaluated. Morphometabolic techniques, CT scan and PET/CT scans were suggestive of malignancy. However, this was not confirmed in the histopathological analysis after its resection. The 18F-FDG-PET/CT does not seem to be a useful tool for early detection of malignancy in JRRP. However, it does increase the diagnostic accuracy of the biopsy as it identifies the most active lesions and, therefore, those most likely to be malignant (AU)
Subject(s)
Humans , Female , Adolescent , Positron-Emission Tomography/instrumentation , Positron-Emission Tomography/methods , Positron-Emission Tomography , Fluorodeoxyglucose F18/analysis , Fluorodeoxyglucose F18/isolation & purification , Papilloma/complications , Papilloma , Nuclear Medicine/methods , Nuclear Medicine/trends , Early Diagnosis , Tracheotomy/methods , TracheotomyABSTRACT
Juvenile recurrent respiratory papillomatosis (JRRP) is an infectious disease caused by the growth of papillomas in the airway. Up to 4% of these cases degenerate into squamous cell carcinoma. We present the case of a 17-year-old female patient with JRRP in which the utility of (18)F-FDG-PET/CT in the characterization of suspicious papillomatous lesions of malignancy is evaluated. Morphometabolic techniques, CT scan and PET/CT scans were suggestive of malignancy. However, this was not confirmed in the histopathological analysis after its resection. The (18)F-FDG-PET/CT does not seem to be a useful tool for early detection of malignancy in JRRP. However, it does increase the diagnostic accuracy of the biopsy as it identifies the most active lesions and, therefore, those most likely to be malignant.