Thomas V Guy^1
1 Ragon Institute of MGH, MIT and Harvard, Boston MA

Systemic sclerosis (SSc) is a severe autoimmune condition that carries the highest excess mortality rate among rheumatic diseases. It is characterised by autoimmunity, chronic inflammation, multi-organ involvement, tissue fibrosis and is refractory to conventional immunosuppressive therapies. While B cell responses in the form of specific autoantibodies have been strongly implicated in SSc, a detailed understanding of the role B cells play is lacking and may help unveil why this disease is often resistant to treatment. 

            

We have performed a broad analysis including multi-colour immunofluorescence of lesional SSc skin samples, flow cytometry of peripheral blood mononuclear cells, as well as single cell RNA-sequencing and HuProt™️ Human Proteome Microarray using SSc patient samples. We have identified a strong extrafollicular B cell signature in the blood and tissues and are currently investigating BCR specificities among dominantly expanded B cell clones in the disease. 

 

These pathogenic B cell signatures may serve as novel tests to better understand disease subtypes, prognosis, and inform therapeutic selection. Ultimately, by characterising the protein targets of B cells, we may also be able to identify the specificities of the underlying CD4+ T cells linked to these aberrant B cell and autoantibody responses which could guide future therapeutic strategies.