Immune regulation by intralymphatic immunotherapy with modular allergen translocation MAT vaccine.

BACKGROUND: Allergen-specific immunotherapy (SIT) faces problems related to side effects and limited efficacy. Direct administration of allergen extracts into lymph nodes induces increased specific IgG production and T-cell responses using significantly lower allergen doses. METHODS: In this study, mechanisms of immune regulation by MAT vaccines in vitro and in allergen-SIT of cat-allergic rhinitis patients, who received 3 inguinal intra-lymph node injections of MAT-Fel d 1 vaccine, were investigated in PBMC and cell cultures for specific T-cell proliferation, Fel d 1-tetramer-specific responses, and multiple immune regulatory molecules. RESULTS: MAT-Fel d 1 vaccine was efficiently internalized by antigen-presenting cells. This was followed by precaspase 1 cleavage to caspase 1 and secretion of IL-1ß, indicating inflammasome activation. Mat-Fel d 1 induced specific T-cell proliferation and an IL-10- and IFN-γ-dominated T-cell responses with decreased Th2 cytokines at 100 times lower doses than Fel d 1. Induction of immune tolerance by MAT-Fel d 1-ILIT involved multiple mechanisms of immune suppression. Early Fel d 1-specific T-cell activation was followed by full T-cell unresponsiveness to allergen after 1 year in the MAT-Fel d 1 group, characterized by increased allergen-specific T regulatory cells, decreased circulating Fel d 1 tetramer-positive cells, increased IL-10 and FOXP3 expression, and change in the HR2/HR1 ratio toward HR2. CONCLUSIONS: This study demonstrates the induction of allergen tolerance after 3 intra-lymph node injections of MAT-Fel d 1 vaccine, mediated by increased cellular internalization of the allergen, activation of inflammasome, and generation of allergen-specific peripheral T-cell tolerance.

Radiologically innocuous breast reduction specimens. Should we send them to pathology lab anyway?

Breast Reduction (BR) is a common procedure around the world. Patients are screened for incidental carcinoma preoperatively by mammography or ultrasonography and BR specimens are sent for pathologic examination postoperatively. Since the incidence of incidental carcinoma is very low, no consensus exist regarding efficiency of pathologic examination. To assess the value of pathologic examination, we examined mammographically and ultrasonographically negative eighty BR specimens from 40 women. Twenty seven women had pathological lesions in their specimens (67,5%). This indicates that, even mammographically and ultrasonographically innocuous, BR specimens may reveal important pathological diagnosis that alters patient management.