Therapeutics: CTLA-4 (CD152); LPS-responsive vesicle trafficking beach and anchor containing (LRBA)

In vitro and patient sample studies suggest inhibitors of lysosomal degradation could help treat patients with autoimmune diseases caused by LRBA deficiency. Positive responses of LRBA-deficient patients to the CTLA-4-Ig fusion protein Orencia abatacept suggest LRBA plays a role in CTLA-4 turnover. Levels of intracellular and cell surface CTLA-4 were lower in T regulatory (Treg) cells from LRBA-deficient patients than in Treg cells from healthy controls. In LRBA-deficient patient-derived T cells, the lysosomal degradation inhibitor chloroquine increased intracellular and cell surface levels of CTLA-4 compared with no treatment. Next steps include cell and structural biological studies of the interaction of LRBA and CTLA-4...