An investigation of the regulation of Sialoadhesin ligands on CD4+ T cells and its potential significance in Systemic Lupus Erythematosus

Sialoadhesin (Sn) is the prototype of Sialic acid binding Immunoglobulin-Like Lectins(SIGLECs). Sn is expressed on macrophages from metalophilic zone and subcapsular sinus in spleen and lymph nodes respectively. Under inflammatory conditions, Sn expression is upregulated on macrophages. Sn was recently found to downregulate CD4+Foxp3+ regulatory T cells (Tregs) in a mouse model of experimental autoimmune Encephalomyelitis (EAE); however the nature of the interaction between Sn and CD4+ T cells is not well characterised. The first aim of this thesis was to investigate the upregulation of Sn ligand (SnL) on CD4+ T cells in vitro. Both Tregs and CD4+Foxp3-T cells upregulate SnL following T cell receptor (TCR) ligation. SnL+CD4+ T cells express a higher state of activation and proliferation compared to SnL- counterparts. Furthermore, engaging SnL on activated CD4+ T cells induces cell death. Experiments performed to analyse the nature of sialylation changes and expression of glycosyltransferases on SnL+ CD4+ T cells, indicated that terminal sialic acids on Nlinked glycans represent a putative ligand for Sn.The second aim of this project was to analyse the role of Sn in a mouse model of systemic lupus erythematosus (SLE). NZB x NZW F1 (BWF1) hybrid model was used for this purpose. Examination of Sn expression on pre-diseased and diseased mice showed that Sn expression is upregulated around the disease onset and went down to pre-disease levels subsequently. This finding might suggest a role for Sn in enhancing cell death and downregulating Treg and therefore augmenting immune dysregulation. Two approaches were used to further study the role of Sn in this model. First, Sn neutralising antibodies were used prophylactically to study the effect on disease severity. Secondly, using speed congenic method, BWF1 mice deficient for Sn were generated. Data presented in this thesis suggest that Sn might play an antiinflammatory role in murine SLE.EThOS - Electronic Theses Online ServiceWellcome TrustGBUnited Kingdo

Differences in the frequency of macrophage and t cell markers between focal and crescentic classes of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis

Funding/Support This study was supported by Tenovus Scotland/Tayside grant award to DK (Grant # T13/15).Peer reviewedPublisher PD

Deceiving proteins! A case of lymphoma and high creatinine

Peer reviewedPublisher PD

Sialoadhesin deficiency does not influence the severity of lupus nephritis in New Zealand Black x New Zealand White F1 mice

Acknowledgements This work was supported by a Wellcome Trust Clinical Fellowship 087078 (to DK) and Wellcome Trust Senior Fellowship 081882MA (to PRC). PAL was funded by a Wellcome Trust Programme Grant (083650/Z/07/Z). We thank the Renal Unit in Ninewells Hospital, Dundee, Scotland, UK, for their support with the immunohistochemistry analysis.Peer reviewedPublisher PD

A novel 4-dimensional live-cell imaging system to study leukocyte-endothelial dynamics in ANCA-associated vasculitis

This work was supported by the Lauren Currie Twilight Foundation, NHS Grampian Renal Endowment Fund and Aberdeen University Development Fund.Peer reviewedPostprintPostprin

A real-world assessment of mycophenolate mofetil for remission induction in eosinophilic granulomatosis with polyangiitis

Funding This study was not supported with specific funding.Peer reviewedPublisher PD

Late onset Pneumocystis jirovecii pneumonia (PJP) in patients with ANCA associated vasculitis

Peer reviewedPostprin

ANCA-associated renal vasculitis is associated with rurality but not seasonality or deprivation in a complete national cohort study

Background Small studies suggest an association between ANCA-associated vasculitis (AAV) incidence and rurality, seasonality and socioeconomic deprivation. We examined the incidence of kidney biopsy-proven AAV and its relationship with these factors in the adult Scottish population.Methods Using the Scottish Renal Biopsy Registry, all adult native kidney biopsies performed between 2014 and 2018 with a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were identified. The Scottish Government Urban Rural Classification was used for rurality analysis. Seasons were defined as autumn (September–November), winter (December–February), spring (March–May) and summer (June–August). Patients were separated into quintiles of socioeconomic deprivation using the validated Scottish Index of Multiple Deprivation and incidence standardised to age. Estimated glomerular filtration rate and urine protein:creatinine ratio at time of biopsy were used to assess disease severity.Results 339 cases of renal AAV were identified, of which 62% had MPA and 38% had GPA diagnosis. AAV incidence was 15.1 per million population per year (pmp/year). Mean age was 66 years and 54% were female. Incidence of GPA (but not MPA) was positively associated with rurality (5.2, 8.4 and 9.1 pmp/year in ‘urban’, ‘accessible remote’ and ‘rural remote’ areas, respectively; p=0.04). The age-standardised incidence ratio was similar across all quintiles of deprivation (p=ns).Conclusions Seasonality and disease severity did not vary across AAV study groups. In this complete national cohort study, we observed a positive association between kidney biopsy-proven GPA and rurality

Selecting teachers and prospective teachers : a meta-analysis

The purpose of this review article was to examine the methods used for the selection of teachers for employment and prospective teachers entering initial teacher education (ITE) programs, and to assess the predictive validity of these methods. We reviewed 32 studies reporting selection methods administered in high-stakes conditions and that included an external (not self-reported) teacher effectiveness outcome measure. The overall effect size was small but significant (r = 0.12, p <.001). Moderator analyses showed that academic and non-academic predictors were both significantly associated with teacher effectiveness measures and that effect sizes were small (but significant) for selection into employment and ITE. We conclude the review by proposing a research agenda that has the potential to enhance educational outcomes by improving the selection of prospective teachers

The extinction of primary polyarteritis nodosa: a modern science success story?

No abstract available