PhD project : Identifying pathogenic autoantibodies in human patients using novel single cell technologies
Autoimmune diseases are a major health problem, but many are difficult to study as relevant samples are rarely available.
A unique model of study consists in the different therapeutic outcomes observed in patients treated for immune thrombocytopenia (ITP), an autoimmune disease caused by antibody-
mediated platelet destruction. The glycoprotein GPIIbIIIa is a frequent (>
40%) target of auto-antibodies. Patients are first depleted of B cells to reduce autoantibody levels and in case of failure (50%), programmed for splenectomy, accompanied by blood sampling and bone marrow aspirates.
This allows access to the three major compartments hosting antibody-secreting cells (ASC) to study their anatomical distribution and the affinity for platelet targets to understand resistance to treatment.
Is there a link between the location of these ASC and the affinity of the auto-antibodies they produce? Are identical ASC clones (i.
e. secreting the same exact antibody) located in different anatomical compartments?
The study of ASC on a single cell level is possible with the DropMap technology that is based on single cell encapsulation in microfluidic droplets and distribution inside an observation chamber, allowing affinity and secretion rate to be calculated for 10,000 cells at a time.
It does not yet, however, allow the identification of the antibody sequence from specific ASC of interest.