Nova Scotia duck tolling retrievers are predisposed to a SLE-related disease complex including immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). IMRD involves symptoms that resemble those seen in systemic autoimmune rheumatic diseases, such as systemic lupus erythematosus, SLE, or SLE-related diseases, in humans. This disease complex involves persistent lameness, stiffness, mainly after resting, and palpable pain from several joints of extremities. The majority of affected dogs display antinuclear autoantibody (ANA)-reactivity. SRMA is manifested in young dogs with high fever and neck stiffness and can be treated with corticosteroids. We have investigated the possible role of MHC class II as a genetic risk factor in IMRD and SRMA etiology. We performed sequence-based typing of the DLA-DRB1, -DQA1, and -DQB1 class II loci in a total of 176 dogs including 51 IMRD (33 ANA-positive), 49 SRMA cases, and 78 healthy controls (two dogs were both IMRD- and SRMA-affected). Homozygosity for the risk haplotype DRB1*00601/DQA1*005011/DQB1*02001 increased the risk for IMRD (OR = 4.9; ANA-positive IMRD: OR = 7.2) compared with all other genotypes. There was a general heterozygote advantage, homozygotes had OR = 4.4 (ANA-positive IMRD: OR = 8.9) compared with all heterozygotes. The risk haplotype contains the five amino acid epitope RARAA, known as the shared epitope for rheumatoid arthritis. No association was observed for SRMA. We conclude that DLA class II is a highly significant genetic risk factor for ANA-positive IMRD. The results indicate narrow diversity of DLA II haplotypes and identify an IMRD-related risk haplotype, which becomes highly significant in homozygous dogs.
We present a simple analytic bound on the quantum value of general
Correlation type Bell inequalities, similar to Tsirelson's bound. It is based
On the maximal singular value of the coefficient matrix associated with the
Inequality. We provide a criterion for tightness of the bound and show that the...
In these HF patients initially free of depression annual incidence rates were high. Several independent predictors allowed identification of patients at particular risk. Although obtained in a selected cohort these findings call, in view of the grave prognosis of HF patients with comorbid depression...
The invariant part (invariant under the action of the automorphisms of the
Homology) of the cohomology of the classifying space of the Torelli group of
Certain high-dimensional, highly connected manifolds, with rational
Coefficients and in a certain range of degrees. This is based on
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