The Influence of HLA-DRB1 Genes on Disease Severity in Rheumatoid Arthritis

Weyand, Cornelia M.; Hicok, Kevin C.; Conn, Doyt L.; Goronzy, Jörg J.

doi:10.7326/0003-4819-117-10-801

Cited by 451 publications

(245 citation statements)

References 25 publications

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“…The exact pathogenesis in still unknown and treatment is non-curative. The presence of shared epitope QKRAA on the HLA-DRβ chain and the presence of rheumatoid factor (RF) have served as long-term outcome predictors of RA [6,32].…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Autoimmunity and oxidatively modified autoantigens

Kurien

Scofield

2008

Autoimmunity Reviews

240

194

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Oxidative damage mediated by reactive oxygen species results in the generation of deleterious byproducts. The oxidation process itself and the proteins modified by these molecules are important mediators of cell toxicity and disease pathogenesis. Aldehydic products, mainly the 4-hydroxy-2-alkenals, form adducts with proteins and make them highly immunogenic. Proteins modified in this manner have been shown to induce pathogenic antibodies in a variety of diseases including systemic lupus erythematosus (SLE), alcoholic liver disease, diabetes mellitus (DM) and rheumatoid arthritis (RA). 8-oxodeoxyguanine (oxidatively modified DNA) and low density lipoproteins (LDL) occur in SLE, a disease in which premature atherosclerosis is a serious problem. In addition, immunization with 4-hydroxy-2-nonenal (HNE) modified 60 kD Ro autoantigen induces an accelerated epitope spreading in an animal model of SLE. Advanced glycation end product (AGE) pentosidine and AGE modified IgG have been shown to correlate with RA disease activity. Oxidatively modified glutamic acid decarboxylase is important in type 1 DM, while autoantibodies against oxidized LDL are prevalent in Behcet's disease. The fragmentation of scleroderma specific autoantigens occurs as a result of oxidative modification and is thought to be responsible for the production of autoantibodies through the release of cryptic epitopes. The administration of antioxidants is a viable untried alternative for preventing or ameliorating autoimmune disease, particularly on account of the overwhelming evidence for the involvement of oxidative damage in autoimmunity. However, this should be viewed in the light of disappointing results obtained with the use of antioxidants in cardiovascular disease. Keywordslupus; autoimmunity; epitopes; autoantibodies; antigens Free radicalsReactive oxygen species (ROS) are oxygen-based molecules possessing high chemical reactivity. These include free radicals (superoxide and hydroxyl radicals) and non-radical species (hydrogen peroxide) which can be produced even at basal conditions by a number of ways. Free radicals are active species containing atoms or molecules with one or more unpaired electrons occupying an outer orbital. They can arise either by the univalent pathway of oxygen

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Section: Rheumatoid Arthritismentioning

confidence: 99%

Autoimmunity and oxidatively modified autoantigens

Kurien

Scofield

2008

Autoimmunity Reviews

240

194

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“…The first suggestion that antibiotic-refractory Lyme arthritis may have an autoimmune component was the demonstration of its association with the HLA-DR4 and HLA-DR2 alleles (25) (27,28) and the DRB5*0101 allele linked to DRB1*1501 (the former DR2 allele) (26). Moreover, patients with antibiotic-refractory arthritis often have T cell recognition of OspA 163-175 (29)(30)(31)(32)(33).…”

Section: Pathogenesis Of Antibiotic-refractory Lyme Arthritismentioning

confidence: 99%

Therapy for Lyme arthritis: Strategies for the treatment of antibiotic‐refractory arthritis

Steere¹,

Angelis²

2006

Arthritis & Rheumatism

207

229

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“…[41][42][43][44][45][46][47][48][49][50] In view of the linkage disequilibrium between DRB1*0401 and the RAGE 82S allele, it will be interesting to specifically test whether DR4 haplotypes containing the RAGE 82S allele have an influence on disease progression and outcome. By analogy with our observations in cultured CHO and human mononuclear cells, we speculate it may be possible to identify a subset of subjects with RA particularly vulnerable to the sequelae of heightened production/activation of proinflammatory mediators.…”

Section: Rage 82s Allele and Association With Rheumatoid Arthritismentioning

confidence: 99%