Understanding the splenic immune response to develop an universal diagnostic and/or therapy tool for acquired thrombotic thrombocytopenic purpura (aTTP)

1. B-cell phenotype & quantification of anti-ADAMTS13 secreting B cells.

Description of the phenotype profile of the spleen-derived B-cells from all aTTP patients (n=8, 3/8 have received RTX before splenectomy) and quantification of the fraction of auto-reactive anti-ADAMTS13 expressing B-cells in comparison of the total IgG-secreting B-cells and investigation of plausible contribution of RTX treatment on the B-cell phenotype/survival in the spleen of relapsing patients.

2.Towards an universal drug.

Screening for the presence of the four by two aTTP patients shared and possible novel CDR3 motifs in spleen-derived B-cells of 6 additional relapsing aTTP patients.

Selection, characterization and affinity determination of the anti-idiotypic DARPins found by screening on the anti-ADAMTS13 Abs of all shared CDR3 motifs by Ribosomal Display.

Determination of the neutralization potential of anti-idiotypic DARPins using monoclonal anti-ADAMTS13 Abs as well as plasma derived Abs from aTTP patients (n=50).