Association of TAP and HLA-DM Genes with Psoriasis in Koreans

Pyo, Chul‐Woo; Hur, Soo-Young; Kim, Yang-Kyum; Kim, Tai‐Gyu; Kim, Taeyoon

doi:10.1046/j.1523-1747.2003.12091.x

Cited by 22 publications

(12 citation statements)

References 56 publications

(53 reference statements)

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“…In psoriasis vulgaris, the G-allele of TAP2_665 has been found to be significantly more frequent than in controls in two of three studies, [7][8][9] and for TAP1_637, the A-allele was found more often in three of four studies. [8][9][10][11] LMP polymorphisms have only been investigated in two studies 8,10 with no significant results. Two small studies, one in HLA-B27-negative ankylosing spondylitis 12 and another in rheumatoid arthritis, 13 indicated that the Gallele in LMP_60 was more frequent in cases than in controls.…”

mentioning

confidence: 90%

Strong associations of psoriasis with antigen processing LMP and transport genes TAP differ by gender and phenotype

Krämer

Illig²,

Grune

et al. 2007

Genes Immun

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Psoriasis, a skin disease with autoimmune features, can be triggered and exacerbated by genetic and environmental factors. Chemicals can break tolerance to self-antigens by interfering with antigen processing and presentation; therefore, proteins involved in antigen processing may affect susceptibility. We test here whether variants of immunoproteasome subunits LMP2 and LMP7, or antigen peptide transport proteins TAP1 (transporters associated with antigen presentation) and TAP2 are associated with psoriasis. We analyzed 7 single-nucleotide polymorphisms in 321 Caucasian (German) psoriasis patients and 235 unrelated controls by time-of-flight mass spectrometry, using the Sequenom platform. We found strong associations of psoriasis with variant alleles of LMP and TAP (OR TAP_687 : 3.3, 95% CI: 1.9-5.7). Genotype effects were generally stronger for males and LMP effects were mainly seen for psoriasis arthropathica. Our results will help define behavioral or drug treatment suggestions to patients and contribute to a better understanding of the role of low molecular weight chemicals in genetic susceptibility to autoimmune diseases. Genes and Immunity (2007) Keywords: immunotoxicology; genetic susceptibility; proteasome; psoriasis arthropathica; environmental factors; SNP Psoriasis is a disease with autoimmune features, affecting about 2% of Caucasians, with major impact on patient's quality of life. Manifestations include red, heavily scaled pruritic plaques, and can affect joints as well. Several distinct but overlapping clinical phenotypes can be distinguished including psoriasis vulgaris and psoriasis arthropathica. Strong evidence suggests a multilocus model of inheritance in association with environmental factors. 1 The etiology of the disease is still unclear. In several cases, however, low molecular weight chemicals (LMWC), such as drugs, were identified as etiologic agents, and variants of genes responsible for metabolizing LMWC are risk factors. 2 A proven concept of immunotoxicology holds that LMWC can break tolerance by interfering with antigen processing and presentation, either exposing cryptic neo-antigens, or by haptenating and thus immunoconverting presented self-antigens.Self-antigen processing and presentation is an essential part of the autoimmune response. Consequently, presenting human leukocyte antigen (HLA) genes, notably HLA-Cw*0602, belong to the identified susceptibility genes of psoriasis. 3 Antigen presentation is essentially dependent on the proteasome, an intracellular protease complex catalyzing important steps in the breakdown of proteins to peptides to be presented as antigens. The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of four rings of 28 non-identical subunits; two rings are composed of seven a-subunits and two rings are composed of seven b-subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave cellular as well as foreign peptides in an ATP/u...

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mentioning

confidence: 90%

Strong associations of psoriasis with antigen processing LMP and transport genes TAP differ by gender and phenotype

Krämer

Illig²,

Grune

et al. 2007

Genes Immun

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“…Several DM polymorphisms have been associated with predisposition to diseases such as Rheumatoid Arthritis (RA), Juvenile RA, medicamentosa-like Dermatitis, Primary Antiphospholipid Syndrome, Psoriasis and atopic Dermatitis (Toussirot et al, 2000;West and Reed, 1999;Yue et al, 2007;Sanchez et al, 2004;Pyo et al, 2003;Kuwata et al, 1996). Additionally, DM polymorphisms may influence vaccine responses (Dhiman et al, 2003;Ovsyannikova et al, 2004).…”

Section: Naturally Occurring Polymorphisms In Immunopeptidome Editorsmentioning

confidence: 99%

Cellular Mechanisms that Edit the Immunopeptidome

Georgiadou¹,

Stratikos

2009

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The adaptive immune response relies on the ability of T-lymphocytes to recognize small antigenic peptides presented on the cell surface by specialized receptors of the Major Histocompatibility Complex (MHC). These peptides are either generated by the degradation of intracellular proteins (MHC class I pathway) or by the degradation of internalized extracellular proteins (MHC class II pathway and cross-presentation pathway). The number of proteins that can be degraded by these pathways runs to the thousands leading to a staggering number of possible peptide fragments. A small subset of these peptides is selected by the cell's processing and presentation mechanisms to be presented on the cell surface by MHC molecules and has been defined as the immunopeptidome. The peptide sequences that comprise the immunopeptidome control the immune response and variations of this peptide repertoire are key to understanding the host's ability to fight pathogens, immune response to cancer as well as predisposition to autoimmunity and allergies. In the last few years it has been established that the composition of the immunopeptidome is regulated by specific cellular mechanisms that influence qualitative and quantitative aspects of the cellular immune response in a process that has been described as antigenic peptide editing. This review explores the current knowledge on these cellular mechanisms and discusses the parallels between editing the MHC class I and class II immunopeptidomes.

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“…immune disorders [33][34][35][36] or not at all [37][38][39][40]. Assigning a role for TAP polymorphism in disease susceptibility will require carefully powered studies with stratification of the data to control for linkage disequilibrium with other genes in the MHC class II region.…”

Section: Human Tap Polymorphism and Diseasementioning

confidence: 99%