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- Lindelöf, Linnea, et al.
(författare)
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A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile
- 2024
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 143
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Tidskriftsartikel (refereegranskat)abstract
- The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE. Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE.
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| 2. |
- Posti, Piia K
(författare)
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The Double Aspect : Gerald Murnane's Visual Poetics
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With its abundance of maps, place names, and landscapes, and with titles like Inland and Landscape with Landscape, Gerald Murnane's fiction exemplifies the dominance of land in Australian literature. Yet, Murnane's fiction differs from most "landscape fiction" in that it depicts an Australia that despite its history of exploration has not yet been fully discovered. Murnane posits a vision of Australia as a place with a twofold character: it is throroughly mapped yet unexplored at the same time.Taking account of that twofold character, this study argues that Murnane's constant preoccupation with matters of vision and visuality is an attempt to flesh out a visual mode that could intimate the other Australia that has been overwritten by the imperial narrative. By investigating the complex interrelations bewteen the structures of vision/visuality and the figures of exile, landscape, and woman in Murnane's narratives, the study traces the emergence of a visual poetics of doubleness as a possible disturbance of colonial landscaping. The various doublings in Murnane's fiction create a gap through which a different perspective may emerge, a perspective that allows an (un)reading of the "Carteisan" gaze inherent in the imperial narrative. The duplication of vision can be understood as a counter-praxis that challenges the scopic regime of "Cartesian perspectivalism".In order to discuss the complexity of this doubleness, the study introduces the two-pronged concept of the double aspect, which denotes both the deconstructive move that enables the (un)reading, and the idosyncratic mode of representation that is at work in Murnane's fiction. Through the double aspect, Murnane's fiction fashions a visual poetics that enables a reconstitution of Australia as a site/sight for continuous re-viewing and rediscovery on an aesthetic plane.
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