B cell characterisation in adult and paediatric liver diseases.

Patel, Arzoo (2024). B cell characterisation in adult and paediatric liver diseases. University of Birmingham. Ph.D.

Preview

Patel2024PhD.pdf
Text - Accepted Version
Available under License Creative Commons Attribution.
Download (13MB) | Preview

Abstract

B cells contribute to the pathology in many diseases such as autoimmune diseases and in many lymphomas. However, there is little literature on liver B cells in health and in disease for paediatric and adult liver diseases. Our aim was to characterise B cell subsets in adult and paediatric livers. We used multiparametric flow cytometry to identify B cell subsets in adult non-cirrhotic and cirrhotic livers, with cholestatic or metabolic disorders. We used immunohistochemistry and immunofluorescence to map the distribution of B cell subsets within liver tissue obtained from biliary atresia (BA) patients at the time of Kasai portoenterostomy (KPE, hilum tissue and wedge tissue from liver periphery) or during orthotopic liver transplantation (explant). We then carried out inflammation-focused transcriptomic analyses to identify differences between non-syndromic and syndromic BA patients and during disease progression. We found that CD24- B cells and age-associated B cells were detected across all adult end-stage liver diseases. We found that paediatric BA hilum samples had increased immune cell infiltration and the presence of B cell and lymphoid aggregates in both non-syndromic and syndromic cases. B cell and lymphoid aggregates mainly consisted of CD20+ CD24- B cells, and CD138+ antibody-secreting cells were rare. CD20+ CD24- B cells in B cell and lymphoid aggregates often expressed IL-6. Nanostring nCounter transcriptomics showed that the hilum was the site of active inflammation during KPE surgery, with pro-inflammatory cytokines being highly expressed. No remarkable differences in genetic profiles were observed between non-syndromic and syndromic BA patients, indicating that liver injury may be similar between the two groups. Our work showed that B cells may contribute to pathology in paediatric and adult liver diseases through the production of inflammatory mediators such as IL-6 and potentially through interactions with T cells. Lymphoid aggregates may also contribute to inflammation observed in the hilum. The hilum region is poorly studies in both adult and paediatric liver diseases and warrants further investigations.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):