ABSTRACT
The neonatal receptor for immunoglobulin G (IgG; FcRn) prevents IgG degradation by efficiently sorting IgG into recycling endosomes and away from lysosomes. When bound to IgG-opsonized antigen complexes, however, FcRn traffics cargo into lysosomes, where antigen processing can occur. Here we address the mechanism of sorting when FcRn is bound to multivalent IgG-opsonized antigens. We find that only the unbound receptor or FcRn bound to monomeric IgG is sorted into recycling tubules emerging from early endosomes. Cross-linked FcRn is never visualized in tubules containing the unbound receptor. Similar results are found for transferrin receptor, suggesting a general mechanism of action. Deletion or replacement of the FcRn cytoplasmic tail does not prevent diversion of trafficking to lysosomes upon cross-linking. Thus physical properties of the lumenal ligand-receptor complex appear to act as key determinants for sorting between the recycling and lysosomal pathways by regulating FcRn entry into recycling tubules.
Subject(s)
Histocompatibility Antigens Class I/metabolism , Lysosomes/metabolism , Receptors, Fc/metabolism , Receptors, Polymeric Immunoglobulin/metabolism , Animals , Cell Line , Cross-Linking Reagents/chemistry , Endosomes/metabolism , Green Fluorescent Proteins/metabolism , Hemagglutinins/metabolism , Histocompatibility Antigens Class I/chemistry , Histocompatibility Antigens Class I/genetics , Humans , Immunoglobulin G/metabolism , Mice , Protein Binding , Protein Structure, Tertiary , Protein Transport , Receptors, Fc/chemistry , Receptors, Fc/genetics , Receptors, Transferrin/metabolism , Recombinant Fusion Proteins/metabolism , beta 2-Microglobulin/metabolismABSTRACT
OBJECTIVE: The objective of our study was to determine the likelihood of malignancy in thyroid nodules and the risk of a nondiagnostic fine-needle aspiration biopsy (FNAB) on the basis of the demographic characteristics of the patients and sonographic features of the nodules. MATERIALS AND METHODS: Between January 2002 and November 2007, 2,338 ultrasound-guided thyroid, thyroid bed, and cervical lymph node FNABs were performed at a tertiary referral center. Entry criteria for our retrospective study were adult patients who underwent thyroid nodule FNAB and had previously undergone diagnostic sonography. From previous reports for 944 thyroid nodules (739 nodules in women and 205 nodules in men), four sonographic features were recorded: longest dimension, morphology, presence of microcalcifications, and presence of lymphadenopathy. The final diagnosis of each nodule was classified as benign, malignant, or nondiagnostic on the basis of surgical pathology when available and cytology otherwise and was analyzed for correlation with individual sonographic features and combinations of features. RESULTS: The prevalence of malignancy and of nondiagnostic FNAB in this study was 11.0% and 11.8%, respectively. Statistically significant (p < 0.05) findings in malignant nodules were younger patient age (< or = 45 years; odds ratio [OR], 1.54) and solid nodule morphology (OR, 2.38). The significant predictors of a nondiagnostic-quality FNAB were older patient age (> 75 years; OR, 1.95) and a nodule > or = 10 mm (OR, 1.45). Adding information about the other evaluated ultrasound features did not lead to a significant result. CONCLUSION: Malignant thyroid nodules tend to be solid (86.5%). Patients older than 75 years showed a clearly increased risk of nondiagnostic FNAB, but to predict a higher risk of malignancy or of nondiagnostic FNAB using ultrasound remains difficult.
