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Comparing HLA shared epitopes in French Caucasian patients with scleroderma.

ABSTRACT: Although many studies have analyzed HLA allele frequencies in several ethnic groups in patients with scleroderma (SSc), none has been done in French Caucasian patients and none has evaluated which one of the common amino acid sequences, (67)FLEDR(71), shared by HLA-DRB susceptibility alleles, or (71)TRAELDT(77), shared by HLA-DQB1 susceptibility alleles in SSc, was the most important to develop the disease. HLA-DRB and DQB typing was performed for a total of 468 healthy controls and 282 patients with SSc allowing FLEDR and TRAELDT analyses. Results were stratified according to patient's clinical subtypes and autoantibody status. Moreover, standardized HLA-DRß1 and DRß5 reverse transcriptase Taqman PCR assays were developed to quantify ß1 and ß5 mRNA in 20 subjects with HLA-DRB1*15 and/or DRB1*11 haplotypes. FLEDR motif is highly associated with diffuse SSc (χ(2) = 28.4, p<10-6) and with anti-topoisomerase antibody (ATA) production (χ(2) = 43.9, p<10-9) whereas TRAELDT association is weaker in both subgroups (χ(2) = 7.2, p = 0.027 and χ(2) = 14.6, p = 0.0007 respectively). Moreover, FLEDR motif- association among patients with diffuse SSc remains significant only in ATA subgroup. The risk to develop ATA positive SSc is higher with double dose FLEDR than single dose with respectively, adjusted standardised residuals of 5.1 and 2.6. The increase in FLEDR motif is mostly due to the higher frequency of HLA-DRB1*11 and DRB1*15 haplotypes. Furthermore, FLEDR is always carried by the most abundantly expressed ß chain: ß1 in HLA DRB1*11 haplotypes and ß5 in HLA-DRB1*15 haplotypes.In French Caucasian patients with SSc, FLEDR is the main presenting motif influencing ATA production in dcSSc. These results open a new field of potential therapeutic applications to interact with the FLEDR peptide binding groove and prevent ATA production, a hallmark of severity in SSc.

SUBMITTER: Azzouz DF

PROVIDER: S-EPMC3352938 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMeasuring care coordination in administrative data facilitates important research to improve care quality.ObjectiveTo compare shared patient networks constructed from administrative claims data across multiple payers.DesignSocial network analysis of pooled cross sections of physicians treating prevalent colorectal cancer patients between 2003 and 2013.ParticipantsSurgeons, medical oncologists, and radiation oncologists identified from North Carolina Central Cancer Registry data linked to Medicare claims (N = 1735) and private insurance claims (N = 1321).Main measuresProvider-level measures included the number of patients treated, the number of providers with whom they share patients (by specialty), the extent of patient sharing with each specialty, and network centrality. Network-level measures included the number of providers and shared patients, the density of shared-patient relationships among providers, and the size and composition of clusters of providers with a high level of patient sharing.ResultsFor 24.5% of providers, total patient volume rank differed by at least one quintile group between payers. Medicare claims missed 14.6% of all shared patient relationships between providers, but captured a greater number of patient-sharing relationships per provider compared with the private insurance database, even after controlling for the total number of patients (27.242 vs 26.044, p < 0.001). Providers in the private network shared a higher fraction of patients with other providers (0.226 vs 0.127, p < 0.001) compared to the Medicare network. Clustering coefficients for providers, weighted betweenness, and eigenvector centrality varied greatly across payers. Network differences led to some clusters of providers that existed in the combined network not being detected in Medicare alone.ConclusionMany features of shared patient networks constructed from a single-payer database differed from similar networks constructed from other payers' data. Depending on a study's goals, shortcomings of single-payer networks should be considered when using claims data to draw conclusions about provider behavior.

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Comparing HLA shared epitopes in French Caucasian patients with scleroderma.

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