Comparative phenotypic analysis of T- and B-lymphocytes in patients with autoimmune lymphoproliferative syndrome and Wiskott-Aldrich syndrome

Sharapova S.O., Paschenko O.E., Guryanova I.E., Migas A.A., Kondratenko I.V., Belevtsev M.V.

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk region, v. Borovliany, Belarus
Russian Children’s Clinical Hospital, Moscow

Objective: To identify phenotypic changes in the formation of T-and B -lymphocytes, regulatory cytokines (BAFF, IL10) in the peripheral blood of patients with autoimmune lymphoproliferative syndrome ( ALPS ) and Wiskott-Aldrich syndrome (WAS) as human model of inborn immunedysregulation.
Methods: Flowcytometric analysis of the following T- and B-cell subsets was performed in 23 patients, 12 patients with ALPS (8 boys, 4 girls and) and 11 boys with WAS, compared to age-matched controls: T cells (CD3 +), T -helper cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+), natural killer cells (CD3-CD16+ CD56+), «thymic emigrants» (CD4+CD31+CD45RA+), regulatory T cells (CD4+CD25+CD127-), transitional (CD19+CD38++IgM++), CD21low, CD21lowCD38low, naпve (CD19+CD27-IgM+/IgD+), switched memory (CD19+CD27+IgM-/IgD-), marginal zone B cells (CD19+CD27+IgM+/IgD+), putative self-reactive B cells (CD19+IgD+IgMlow), putative regulatory B cells (CD19+CD24++CD38++), functionally immature B lymphocytes (CD19+CD21-, CD19+ CD21-CD38-, CD19+CD21-CD38++) and BAFF, IL10 serum levels were evaluated by ELISA assay.
Results and conclusions: Immunological manifestation of dysregulation by T -cell immunity is the reduction of recent thymic emigrants (CD4+CD45RA+CD31+) and regulatory T-lymphocytes (CD4+ CD25+CD127-) in patients with ALPS regardless the presence of mutation in the Fas gene and WAS associated with autoimmune pathology. Immunedysregulation appears relative expansion of B-lymphocytes with putative autoreactive properties (CD19+IgD+IgM-/low), functionally immature B lymphocytes (CD19+CD21-CD38-) in ALPS patients with genomic Fas mutation and WAS with related autoimmune diseases.