Cutting Edge: Molecular Portrait of Human Autoimmune Disease

Abstract

Autoimmune diseases affect 3–5% of the population, are mediated by the immune response to self-Ags, and are characterized by the site of tissue destruction. We compared expression levels of >4,000 genes in PBMC of control individuals before and after immunization to those of individuals with four distinct autoimmune diseases. The gene expression profile of the normal immune response exhibits coordinate changes in expression of genes with related functions over time. In contrast, each individual from all autoimmune diseases displays a similar gene expression profile unrelated to the pattern of the immunized group. To our surprise, genes with a distinct expression pattern in autoimmunity are not necessarily “immune response” genes, but are genes that encode proteins involved in apoptosis, cell cycle progression, cell differentiation, and cell migration.

Expression of a pathogen-response program in peripheral blood cells defines a subgroup of Rheumatoid Arthritis patients

“…37 We found evidence for diminished apoptosis in the RA A group, which suggests that a defect in apoptosis may contribute to the autoimmune process, as has been suggested before. 38 The increased ACPA levels in the RA A patients might therefore be related to defects in the apoptotic pathway. Of interest is the recent observation that approximately half of the RA patients show antibody reactivity to citrullinated EBV-derived peptide, which correlates with ACPA levels.…”

Expression levels for many genes in human peripheral blood cells are highly sensitive to ex vivo incubation

“…Diseases characterized by inflammation and by activated immune responses are obvious targets for initial experiments, and indeed a number of groups, including our own, have initiated such studies. 3,5,18,19 In order for the information from peripheral blood cell gene expression to be optimally useful for translational clinical studies, it will be important to attempt to control as many variables as possible. Many factors are known to dynamically influence the numbers and function of peripheral blood cells and the relative proportions of cells at a given point in time.…”

“…[3][4][5][6][7] Our work to date has focused on the examination of blood cells in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). 5 RA is a chronic, inflammatory arthritis associated with progressive damage to synovial joints together with extraarticular manifestations.…”

Postprandial antioxidant gene expression is modified by Mediterranean diet supplemented with coenzyme Q10 in elderly men and women

“…Peripheral blood mononuclear cells (PBMCs) are a subset of white blood cells, which include lymphocytes and monocytes, and play a critical role in the immune system. Various studies showed disease-characteristic gene expression patterns in PBMCs (Mass et al 2002;Burczynski and Dorner 2006) and they can be easily and repeatedly collected in sufficient quantities in contrast to the more invasive sampling of adipose, muscle and liver tissues, among others (de Mello et al 2008). However, little is known of nutritional effects on PBMCs gene expression patterns.…”