The serum hallmark of primary biliary cirrhosis (PBC) is the presence of anti-mitochondrial antibodies (AMA), found in 95% of patients. However, nearly every patient with PBC, including those who are AMA-negative, has an elevation in serum IgM. This hyper-IgM is neither representative of other Ig isoforms, nor is due to the levels of AMA. In fact, we have recently reported that the hyper-IgM is an innate immune response and can be induced with CpG-B with concurrent up-regulation of toll-like receptor 9 (TLR9). Based on these observations, we performed a two-tier study. First, we quantitated TLR9 genotypes in patients with PBC and controls and correlated these data with the B cell response to CpG-B. Second, based on these data, we performed an extensive TLR9 genotyping in a large cohort of patients and controls. We report herein that the 2848 AA TLR9 genotype is associated with enhanced gene expression and higher frequency of intracellular IgM+ B cells following CpG stimulation. Interestingly, however, despite the functional association, there is no difference in the distribution of TLR9 genotypes between patients and controls. Our data emphasize the importance of dissecting the innate immune response in PBC.
|Titolo:||Genetic polymorphisms of toll-like receptor 9 influence the immune response to CpG and contribute to hyper-IgM in primary biliary cirrhosis|
|Parole Chiave:||Bacterial motifs; Genetic polymorphisms; Innate immunity; Primary biliary cirrhosis|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||giu-2005|
|Digital Object Identifier (DOI):||10.1016/j.jaut.2005.03.002|
|Appare nelle tipologie:||01 - Articolo su periodico|