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Conference paperFalcone S, Nicol T, Blease A, et al., 2022,
Journal articleGulati K, Edwards H, Prendecki M, et al., 2022,
Journal articleBeckwith H, Lightstone L, McAdoo S, 2022,
There is increasing understanding that a multifaceted interplay of sex-dependent genetic and immune dysregulation underpins the development of glomerular disorders. Regional and ethnic variations in glomerular disease incidence make delineating the effects of sex and gender on disease pathophysiology more complex, but there is a marked paucity of research in this area. This review article presents a summary of the current understanding of sex and gender in glomerular disease, highlighting the broader effects of sex and gender on autoimmunity, clinical presentations, and pathophysiology of individual glomerular diseases, as well as exploring sex, gender, and glomerular disease within a wider socioenvironmental context. It is important to specifically consider the effects of sex and gender when presenting and analyzing clinical and scientific studies on glomerular disease. Failure to do so risks promoting disparities within health care provision, neglecting opportunities to identify sex-specific biomarkers, and potentially hindering the development of sex-specific therapies.
Journal articleTempest-Roe S, Prendecki M, McAdoo S, et al., 2022,
Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization, Scientific Reports, Vol: 12, ISSN: 2045-2322
Antibody mediated rejection is a major cause of renal allograft loss. Circulating preformed donor specific antibodies (DSA) can result as a consequence of blood transfusion, pregnancy or prior transplantation. Current treatment strategies are limited due to partial or transient efficacy, adverse side-effects or patient unsuitability. Previous in vivo studies exploring autoimmune diseases have shown that spleen tyrosine kinase (SYK) signalling is involved in the development of pathogenic autoantibody. The role of SYK in allogenic antibody production is unknown, and we investigated this in a rodent model of sensitization, established by the transfusion of F344 whole blood into LEW rats. Two-week treatment of sensitized rats with selective SYK inhibitor fostamatinib strongly blocked circulating DSA production without affecting overall total immunoglobulin levels, and inhibition was sustained up to 5 weeks post-completion of the treatment regimen. Fostamatinib treatment did not affect mature B cell subset or plasma cell levels, which remained similar between non-treated controls, vehicle treated and fostamatinib treated animals. Our data indicate fostamatinib may provide an alternative therapeutic option for patients who are at risk of sensitization following blood transfusion while awaiting renal transplant.
Journal articleWalsh M, Collister D, Zeng L, et al., 2022,
Journal articlePage TH, Chiappo D, Brunini F, et al., 2022,
Journal articleDhaun N, McAdoo SP, 2022,
Journal articleWoollard K, 2022,
Chronic kidney disease mediates cardiac dysfunction associated with increased resident cardiac macrophages, BMC Nephrology, Vol: 23, Pages: 1-15, ISSN: 1471-2369
Background – The leading cause of death in end-stage kidney disease is related tocardiovascular disease. Macrophages are known to be involved in both chronic kidney disease(CKD) and heart failure, however their role in the development of cardiorenal syndrome is lessclear. We thus sought to investigate the role of macrophages in uremic cardiac disease.Methods – We assessed cardiac response in two experimental models of CKD and testedmacrophage and chemokine implication in monocytopenic CCR2-/- and anti-CXCL10 treatedmice. We quantified CXCL10 in human CKD plasma and tested the response of human iPSCderived cardiomyocytes and primary cardiac fibroblasts to serum from CKD donors. Results– We found that reduced kidney function resulted in the expansion of cardiac macrophages,in particular through local proliferation of resident populations. Influx of circulating monocytescontributed to this increase. We identified CXCL10 as a crucial factor for cardiac macrophageexpansion in uremic disease. In humans, we found increased plasma CXCL10 concentrationsin advanced CKD, and identified the production of CXCL10 in cardiomyocytes and cardiacfibroblasts. Conclusions – This study provides new insight into the role of the innate immunesystem in uremic cardiomyopathy.
Journal articlePugh D, Karabayas M, Basu N, et al., 2022,
Large-vessel vasculitis (LVV) manifests as inflammation of the aorta and its major branches and is the most common primary vasculitis in adults. LVV comprises two distinct conditions, giant cell arteritis and Takayasu arteritis, although the phenotypic spectrum of primary LVV is complex. Non-specific symptoms often predominate and so patients with LVV present to a range of health-care providers and settings. Rapid diagnosis, specialist referral and early treatment are key to good patient outcomes. Unfortunately, disease relapse remains common and chronic vascular complications are a source of considerable morbidity. Although accurate monitoring of disease activity is challenging, progress in vascular imaging techniques and the measurement of laboratory biomarkers may facilitate better matching of treatment intensity with disease activity. Further, advances in our understanding of disease pathophysiology have paved the way for novel biologic treatments that target important mediators of disease in both giant cell arteritis and Takayasu arteritis. This work has highlighted the substantial heterogeneity present within LVV and the importance of an individualized therapeutic approach. Future work will focus on understanding the mechanisms of persisting vascular inflammation, which will inform the development of increasingly sophisticated imaging technologies. Together, these will enable better disease prognostication, limit treatment-associated adverse effects, and facilitate targeted development and use of novel therapies.
Journal articleAustin K, Janagan S, Wells M, et al., 2022,
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