ABSTRACT
Engagement of cytokine receptors by specific ligands activate Janus kinase-signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyte behavior remain incompletely defined. Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a potent regulator of B cell differentiation. We have studied patients with inactivating mutations in STAT1 or STAT3 to dissect their contribution to B cell function in vivo and in response to IL-21 in vitro. STAT3 mutations dramatically reduced the number of functional, antigen (Ag)-specific memory B cells and abolished the ability of IL-21 to induce naive B cells to differentiate into plasma cells (PCs). This resulted from impaired activation of the molecular machinery required for PC generation. In contrast, STAT1 deficiency had no effect on memory B cell formation in vivo or IL-21-induced immunoglobulin secretion in vitro. Thus, STAT3 plays a critical role in generating effector B cells from naive precursors in humans. STAT3-activating cytokines such as IL-21 thus underpin Ag-specific humoral immune responses and provide a mechanism for the functional antibody deficit in STAT3-deficient patients.
Subject(s)
Cell Differentiation/physiology , Immunologic Memory/physiology , Interleukins/immunology , Plasma Cells/immunology , STAT3 Transcription Factor/immunology , Signal Transduction/physiology , Antibody Formation/physiology , Antigens/genetics , Antigens/immunology , Humans , Immunoglobulins/genetics , Immunoglobulins/immunology , Interleukins/genetics , Plasma Cells/cytology , STAT1 Transcription Factor/genetics , STAT1 Transcription Factor/immunology , STAT3 Transcription Factor/genetics , Time FactorsABSTRACT
Anaphylaxis in the setting of general anesthesia is a rare but potentially lethal event. The investigation of severe reactions is important for confirming the clinical diagnosis and identifying likely causative agents and safe agents that may be used in the future. Many comprehensive reports have described the testing protocol of individual specialized units, whereas there has been no standardization of testing techniques or formal assessment of these tests' diagnostic accuracy. We review the literature with reference to the recently published standards for reporting of diagnostic accuracy (STARD) and make recommendations for future studies of diagnostic accuracy in the field.
