P99 Effector DN2 B cells are expanded in a mixed ancestry colombian SLE patient population

Background Double Negative (DN) B lymphocytes are expanded in Systemic Lupus Erythematosus (SLE). Specifically, DN2 cells are a DN subset recently characterized and are functionally plasmablasts precursors. DN2 frequency is higher in SLE patients of African American ancestry and is associated with disease activity and nephritis. The population of Colombia has a mixture of European, indigenous American, and African ancestries. It is not known if Colombian patients have the same DN B cell distributions previously described and if they are associated with clinical manifestations. Methods 40 SLE patients who met the 1982 ACR criteria and 17 Healthy Controls matched by age and gender were recruited from Medellin, Colombia. Cryopreserved peripheral lymphocytes were analyzed by multiparametric Flow Cytometry. DN cells were characterized using CD3, CD19, CD27, IgD, CD11c, and CD21 markers. Results SLE patients showed similar DN and DN2 distributions comparable to those described in African American patients. DN and DN2 cells were higher in patients with active disease, especially with severe activity. Patients with active nephritis and a history of nephritis had the same increase in DN and DN2. The evaluation of DN and DN2 in patients receiving treatment with mycophenolate and or cyclophosphamide also showed this increase. Conclusions The alterations previously described in the frequency of DN and DN2 B cells are also found in Colombian patients. DN2 are generated through an extrafollicular differentiation pathway, which has an essential role in the autoantibodies production on SLE. These findings suggest a relevant contribution of an extrafollicular DN2 production on SLE pathophysiology in patients with mixed ancestry, as described before, for African American patients.