Update: HLA-DQ Associations with Autoimmune Disease

Altmann, Daniel M.

doi:10.3109/08916939309077360

Cited by 14 publications

(11 citation statements)

References 36 publications

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“…Interestingly, TNF has been shown to induce expression of the mitochondrial manganous SOD (MnSOD; Wong and Goeddel, 1988;Sachs, 1990;Altmann, 1992). The present results indicate the importance of SOD in explaining the pathogenic evolution of Chagas disease.…”

Section: Anti-oxidant Enzymes and Indeterminate Chagasmentioning

confidence: 51%

The anti-oxidant defence response in individuals with the indeterminate form of Chagas disease (American trypanosomiasis)

Pérez-Fuentes

Torres‐Rasgado

Salgado-Rosas

et al. 2008

Annals of Tropical Medicine & Parasitology

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In previous studies in animal models, Trypanosoma cruzi-induced oxidative stress and damage have sometimes been controlled by the host's anti-oxidant defence responses. The role of the anti-oxidant defence responses, such as the activities of the anti-oxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD), in protection against inflammation and damage have now been investigated in humans infected with T. cruzi. The subjects were 32 asymptomatic but seropositive individuals with the indeterminate form of Chagas disease, 18 symptomatic and seropositive patients with the chronic disease, and 50 seronegative and apparently healthy controls. The inflammatory process was explored using serum concentrations of tumour necrosis factor (TNF) and NO. The serum concentrations of GPx in the patients in the indeterminate phase of infection were similar to those in the controls but much higher than those in the chronic cases (P=0.001). The serum concentrations of SOD in the patients in the indeterminate phase of infection were not only significantly higher than those in the cases of chronic Chagas disease (P=0.0004) but also significantly higher than those in the controls (P<0.001). The seropositive subjects had significantly higher serum concentrations of TNF and NO than the controls (P<0.01 for each) and the cases of chronic Chagas disease had significantly higher serum concentrations of TNF and NO than the subjects with the indeterminate form of the disease (P<0.01 for each). It therefore appears that the host's anti-oxidant defence responses (at least in terms of elevated concentrations of SOD) may inhibit inflammation during the indeterminate phase of Chagas disease.

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Section: Anti-oxidant Enzymes and Indeterminate Chagasmentioning

confidence: 51%

The anti-oxidant defence response in individuals with the indeterminate form of Chagas disease (American trypanosomiasis)

Pérez-Fuentes

Torres‐Rasgado

Salgado-Rosas

et al. 2008

Annals of Tropical Medicine & Parasitology

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“…Disease association studies looking at HLA class II polymorphisms are confounded by the fact that linkage disequilibrium makes it difficult to distinguish contributions of HLA-DR and -DQ polymorphisms [19]. Indeed, it is often virtually impossible to separate the potential functional contribution to disease of gene products from the two loci [20].…”

Section: Evidence For a Class II Association With Hla-dr1 Dq5mentioning

confidence: 99%

“…of HLA-DR and -DQ polymorphisms [19]. Indeed, it is often virtually impossible to separate the potential functional contribution to disease of gene products from the two loci [20].…”

Section: Evidence For a Class II Association With Hla-dr1 Dq5mentioning

confidence: 99%

Human leucocyte antigen class II association in idiopathic bronchiectasis, a disease of chronic lung infection, implicates a role for adaptive immunity

Boyton

Smith

Jones

et al. 2008

Clinical and Experimental Immunology

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SummaryThe aetiology of idiopathic bronchiectasis, a lung disease where chronic inflammation and bacterial infection leads to progressive lung damage, is unknown. A possible role for natural killer cells has been highlighted previously. However, a role for adaptive immunity is suggested by the presence of CD4 and CD8 T cells in diseased lung tissue. Evidence of a human leucocyte antigen (HLA) class II disease association would further implicate a role for adaptive immunity. To establish if there is any HLA association, we analysed HLA-A, HLA-B, HLA-DQA1, HLA-DQB1 and HLA-DRB1 alleles in patients with idiopathic bronchiectasis and controls. Genomic DNA from 92 adults with idiopathic bronchiectasis and 101 healthy controls was analysed by polymerase chain reaction with sequence-specific primers. We found an increase in the prevalence of HLA-DRB1*01 DQA1*01/DQB1*05 genes in idiopathic bronchiectasis; that is, the HLA-DR1, DQ5 haplotype (odds ratio 2·19, 95% confidence interval 1·15-4·16, P = 0·0152) compared with control subjects. The association with HLA-DR1, DQ5 implicates a role for CD4 T cells restricted by these molecules in susceptibility to the progressive lung damage seen in this disease. This may operate either through influencing susceptibility to specific pathogens or to self-reactivity and requires further investigation.

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“…Many MS genetics studies suggest DRB1*1501 as the primary risk factor for increased susceptibility to MS (9). However, because of the strong linkage disequilibrium between the DR and DQ alleles (10) there has been a lack of agreement on whether the HLA-DR15 allele or the HLA-DQ6 class II allele, or both, is a bona fide MS-predisposing immune response gene conferring risk of susceptibility to MS (5,11). Some illumination has come from looking at small disease cohorts in small non-Caucasian ethnic groups or from looking at large numbers of haplotypes in Caucasian patients.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

HLA-DQB10602 Determines Disease Susceptibility in a New “Humanized” Multiple Sclerosis Model in HLA-DR15 (DRB11501;DQB1*0602) Transgenic Mice

Kaushansky

Altmann

Ascough

et al. 2009

The Journal of Immunology

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The susceptibility to multiple sclerosis (MS), a chronic neurological autoimmune disease that primarily targets CNS myelin, has long been associated with HLA class-II genes. Although several other HLA and non-HLA disease predisposing alleles have been identified, alleles of the HLA-DR15 haplotype (DRB1*1501, DRB5*0101, and DQB1*0602) remain the strongest susceptibility factor. Many studies have suggested that the HLA-DRB1*1501 allele determines MS-associated susceptibility. However, due to strong linkage disequilibrium within the HLA class II region, it has been difficult to unequivocally determine the relative roles of the DRB1*1501 and DQB1*0602 products. In this study we use HLA class-II transgenic mice to illuminate the relative contributions of the DRB1*1501 and DQB1*0602 alleles or their combination to susceptibility toward a new “humanized” MS-like disease induced by myelin-associated oligodendrocytic basic protein (MOBP). Although many immunological studies have focused overwhelmingly on the role of the HLA-DRB1*1501 product in MS, we show that HLA-DRB1*1501 transgenics are refractory to MOBP disease induction, whereas the HLA-DQB1*0602 transgenics are susceptible via T cells reactive against MOBP15–36 and MOBP55–77 encephalitogenic epitopes. Although both transgenics react against these epitopes, the MOBP15–36- and MOBP55–77-reactive T cells are of Th2-type in HLA-DRB1*1501 transgenics and are pathogenic Th1/Th17 cells in the HLA-DQB1*0602 transgenic mice. This new humanized model of MS further implicates autoimmunity against MOBP in MS pathogenesis, provides the first evidence of pathogenic HLA-DQ-associated anti-myelin autoimmunity, and is the first to offer a rationale for HLA-DQB1*0602 association with MS. These findings have important bearing on the candidacy of the DQB1*0602 allele as a genetic risk factor for MS.

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Update: HLA-DQ Associations with Autoimmune Disease

Cited by 14 publications

References 36 publications

The anti-oxidant defence response in individuals with the indeterminate form of Chagas disease (American trypanosomiasis)

The anti-oxidant defence response in individuals with the indeterminate form of Chagas disease (American trypanosomiasis)

Human leucocyte antigen class II association in idiopathic bronchiectasis, a disease of chronic lung infection, implicates a role for adaptive immunity

HLA-DQB10602 Determines Disease Susceptibility in a New “Humanized” Multiple Sclerosis Model in HLA-DR15 (DRB11501;DQB1*0602) Transgenic Mice

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Update: HLA-DQ Associations with Autoimmune Disease

Cited by 14 publications

References 36 publications

The anti-oxidant defence response in individuals with the indeterminate form of Chagas disease (American trypanosomiasis)

The anti-oxidant defence response in individuals with the indeterminate form of Chagas disease (American trypanosomiasis)

Human leucocyte antigen class II association in idiopathic bronchiectasis, a disease of chronic lung infection, implicates a role for adaptive immunity

HLA-DQB1*0602 Determines Disease Susceptibility in a New “Humanized” Multiple Sclerosis Model in HLA-DR15 (DRB1*1501;DQB1*0602) Transgenic Mice

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HLA-DQB10602 Determines Disease Susceptibility in a New “Humanized” Multiple Sclerosis Model in HLA-DR15 (DRB11501;DQB1*0602) Transgenic Mice