Autoimmune rheumatologic diseases

Poster

Characterizing the Plasmablast Antibody Repertoire in Patients with Aire Deficiency

Thursday, June 15
5:45 PM - 7:00 PM

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in AIRE, a transcription factor necessary for central tolerance through the expression of tissue specific antigens in the thymus. APECED patients are known to produce high-affinity neutralizing autoantibodies against a pool of shared auto-antigens that may contribute to some of the hallmark clinical features of the disorder, along with additional private autoantibodies that may reflect patient-specific disease manifestations. To further characterize the impact of AIRE deficiency on the B cell response, we used a cell barcoding technology to sequence the paired heavy and light chains of individual plasmablasts derived from the blood of APECED patients. Through bioinformatic analysis of the sequence datasets, we identified clonally expanded lineages of affinity-matured plasmablasts, which we hypothesize to play a role in disease pathogenesis. To elucidate the roles of their encoded antibodies, we recombinantly expressed representatives from select highly-mutated clonal families. We are characterizing the binding properties of these antibodies using human cytokine and protein arrays, as well as evaluating their functional properties through in vitro immune cell assays.  Our approach will allow us to gain further insight into the immune dysregulation that arises from AIRE deficiency and the pathogenic mechanisms that underlie APECED.


 

Julia Z. Adamska

Stanford University; VA Palo Alto Health Care System

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    Justin A. Jarrell

    Stanford University; VA Palo Alto Health Care System

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      Muthulekha Swamydas

      National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH)

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        Michail S. Lionakis

        National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH)

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          William H. Robinson

          Stanford University; VA Palo Alto Health Care System

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