Role Of Memory B Cells In Antibody Mediated Rejection: A Proof Of Concept

Introduction Antibody mediated rejection (AMR) diagnosis, monitoring and treatment is exclusively based on circulating donor specific antibodies (DSA). However, DSA often fails to predict and diagnose AMR, since it does not represent the whole HLA-specific memory B cell (mBc) repertoire. Central and peripheral donor (HLA)-sp B-cell responses may offer a new diagnostic and therapeutic target. Case Report 44 years old female affected from an advanced Chagasic cardiomyopathy refractory to therapy was listed for heart transplant with a PRA of 67% in 03/2019. She was transplanted in 11/2019, with a negative CDC-XM. Induction was based on basiliximab and tacrolimus-based triple therapy with Mycophenolate mofetil and steroids. Despite a negative CDC-XM, 5 C3q-fixing DSA were detected (A3, DR1, DR7, DPB1, DQ2 and DQ5). Post-op was uneventful and biventricular function was preserved at day 7. The 14-day endomyocardial biopsy showed acute cellular rejection G2R and p(AMR)1 i+ with persistent DSAs. High doses of esteroids, IVIG and plasmapheresis were started. The SAB assay on day 25 showed persistent detection of all DSA, although with lower MFI levels. To characterize B-cell immune response, we used a novel HLA-specific B-cell FluorSpot assay. Bone marrow aspirate and peripheral blood demonstrated high frequencies of donor(HLA)-sp IgG-producing plasma cells and circulating donor-specific mBc, respectively, against different donor(HLA)-Ag specificities (figure 1). Given patient\u0027s favorable evolution, with two main immune compartments showing anti-donor B-cell activation requiring a combined immunosuppressive therapy, no additional treatment was started. At 12 months of follow-up the patient remains clinically stable with negative ACR/pAMR EMB. Summary Our data highlights the need of a more accurate evaluation of the anti-donor humoral immune response leading to DSA production in order to refine current immune-risk stratification and ultimately help decision-making regarding the type of rescue immunosuppressive therapy.