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Abstract

120 IDDM = insulin-dependent diabetes mellitus; IFN = interferon; IL = interleukin; MS = multiple sclerosis; PCR = polymerase chain reaction; PBMC = peripheral blood mononuclear cell; RA = rheumatoid arthritis; SDA = Symbolic discriminant analysis; SLE = systemic lupus erythematosus; SLEDAI = SLE disease activity index. Arthritis Research & TherapyVol 6 No 3 Olsen et al. IntroductionThe relatively new technology of DNA microarrays has made it feasible to measure the expression levels of thousands of genes in small biological samples [1]. It has been suggested that this methodology might be especially useful in analyzing the complex and parallel changes that occur within cells and tissues of the immune system in normal and pathologic states [2]. Much of the early work using DNA microarrays was in the field of oncology; other studies have examined host responses to infectious agents or drugs [3]. The gene array approach is especially wellsuited to the type of multifactorial analysis that is needed to unravel the causes of human autoimmune disorders that involve both complex genetics and environmental factors [4,5]. Studies in autoimmune disease have included the use of biopsy samples from affected patients, targeting tissues such as synovium, brain or skin [6][7][8][9]. While this approach can offer insights for some disease subsets, it does not permit study of all afflicted patients and cannot be applied to early phases of disease when therapeutic interventions are most likely to be useful. As an alternative, we and others have hypothesized that due to the systemic nature of autoimmune disease, clinically relevant changes in gene expression should be observed in peripheral blood mononuclear cells (PBMCs). Using peripheral blood as the source of gene expression material offers the possibility of sampling any individual at any time and also has the potential to detect early pathogenetic and prognostic factors. This review will examine studies in autoimmune disease, focusing on the utility of peripheral blood samples to identify genes of interest. The potential for this approach to provide insights into disease pathogenesis and to aid with diagnosis and management are also discussed. Approach to the study of autoimmune diseaseA relatively small number of microarray studies in autoimmunity have been reported [3]. Some of these have AbstractThe relatively new technology of DNA microarrays offers the possibility to probe the human genome for clues to the pathogenesis and treatment of human disease. While early studies using this approach were largely in oncology, many new reports are emerging in other fields including infectious diseases and pharmacology, and applications in autoimmunity have been recently reported by our group and others. Some of these investigations have examined animal models of autoimmune disease, but a number of human studies have also been carried out. Of special interest are those that have used peripheral blood samples because, unlike tissue biopsies, these are readily available from all subje...

p21 Ras/Impedes Mitogenic Signal Propagation Regulates Cytokine Production and Migration in CD4 T Cells

“…By mediating disengagement of Ksr, Imp may interfere with Ksrinduced protection of the bowel mucosa, thereby permitting exacerbation of the inflammatory injury. Also, studies of gene profiles in peripheral blood mononuclear cells have shown that the expression of BRCA1, which is thought to associate with Imp, is down-regulated in families at risk for autoimmune diseases (54). Although the significance of this alteration is not clear, one may speculate that decreased expression of BRCA1 supports the interaction between Imp and Ksr and ultimately leads to the down-regulation of signal transduction in T cells.…”

Versican and the control of inflammation

“…While accumulation of versican during the inflammatory response can originate in the stromal connective tissue, a number of past as well as more recent studies have identified versican as a gene which is upregulated in monocytes in a number of pro-inflammatory states, such as myocardial infarction (Toeda et al, 2005), coronary stenosis (Wingrove et al, 2008), autoimmunity (Masuda et al, 2013; Olsen et al, 2004; Shou et al, 2006), and in response to pro-inflammatory stimulants such as lipopolysaccharide (LPS) (Lang et al, 2002) and hypoxia (Asplund et al, 2011; Asplund et al, 2009). In addition, the versican gene is differentially expressed in M1 macrophages, as opposed to M2 macrophages, as they differentiate from monocytes (Asplund et al, 2011; Martinez et al, 2006).…”

Upcoming value of gene expression analysis in rheumatology

“…Агенты, блокирующие TNFa, улучшают состояние больных РА, особенно в случае позитивности к АЦЦП, поэтому РА считается заболеванием, зависимым от TNFa [17]. При этом больные РА с более высокими уровнями синовиального воспаления и экспрессии TNFa в синовии [18], а также при увеличении экспрессии генов бета-рецептора IL2, SH2 домена 2А и GOS2 в периферической крови более чувствительны к блокаде TNFa [19].…”

“…Более того, изменения, происходящие в тканях и крови больных РА взаимосвязаны, поскольку показано, что в клетках крови больных РА повышена экспрессия генов, регулирующих морфогенез кости и хряща, по сравнению со здоровыми лицами [144] и отмечена корреляция экспрессии генов в крови и повреждённых тканях больных РА [145][146][147][148]. Ранее были выявлены различия в экспрессии ряда генов, ассоциированных с РЗ, по сравнению со здоровыми лицами не только в таргетных органах, но и в крови больных [17,[149][150][151].…”