Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients

<p>Abstract</p> <p>Background</p> <p>A strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sample sizes, or because of lack of accurate clinical subgrouping.</p> <p>Subjects and methods</p> <p>In this study we HLA typed a large patient population (n = 754) recruited from one single centre. Patients were sub-grouped into those with Löfgren's syndrome (LS) (n = 302) and those without (non-Löfgren's) (n = 452), and the majority of them were clinically classified into those with recovery within two years (resolving) and those with signs of disease for more than two years (non-resolving). PCR was used for determination of HLA-DRB1 alleles. Swedish healthy blood donors (n = 1366) served as controls.</p> <p>Results</p> <p>There was a dramatic difference in the distribution of HLA alleles in LS compared to non-LS patients (p = 4 × 10^-36). Most notably, DRB1*01, DRB1*03 and DRB1*14, clearly differed in LS and non-LS patients. In relation to disease course, DRB1*07, DRB1*14 and DRB1*15 generally associated with, while DRB1*01 and DRB1*03 protected against, a non-resolving disease. Interestingly, the clinical influence of DRB1*03 (good prognosis) dominated over that of DRB1*15 (bad prognosis).</p> <p>Conclusions</p> <p>We found several significant differences between LS and non-LS patients and we therefore suggest that genetic association studies in sarcoidosis should include a careful clinical characterisation and sub-grouping of patients, in order to reveal true genetic associations. This may be particularly accurate to do in the heterogeneous non-LS group of patients.</p

The socio-logic of knowledge-in-formation between discovery and error: some considerations from ‘normal science’ under exceptional conditions

A sociology of knowledge of a specific kind, namely that emerging from observations on the work of scientific thought collectives, is what Thomas Kuhn acknowledges as Ludwik Fleck’s (Denkstile und Tatsachen. Gesammelte Schriften und Zeugnisse, Suhrkamp, Berlin, 1936) influence on his own Structure of Scientific Revolutions (1962). Yet the relationship between thought and collective that turns out to be one of the central problematics in Fleck’s thought, remains troubling to Kuhn. The reservations expressed by Kuhn go to the core of Fleck’s conceptualization of the structures, roles, scientific achievements, illusions, and errors of thought collectives, as well as to the sociology of knowledge with which he is credited, but which remains a theoretical blindspot. I would here like to take a closer look at this problematic, with a view to specifying the nature and the dynamic of a ‘sociology of knowledge’ that a leading thought would engender in a scientific collective, in its refractions between internal and external conditions of knowledge formation, operationalized under conditions of scientific work in Nazi concentration camps, as they were retrospectively recounted by Fleck (Cognition and fact: material on Ludwik Fleck, D. Reidel, Dordrecht, 1946).http://link.springer.com/journal/110592015-12-31hb201