LYMPHOPROLIFERATIVE DISEASE OF LAK CELL PRECURSOR LARGE GRANULAR LYMPHOCYTES IN ASSOCIATION WITH CELIAC-DISEASE

We have investigated a case of lymphoproliferative disease of large gr anular lymphocytes (LDGL) occurring in association with celiac disease , anemia, neutropenia, and carcinomas of the endometrium, breast, and skin. The large granular lymphocyte (LGL) proliferation was monoclonal , T cell in origin, with T cell receptor beta-chain gene rearrangement , and a CD3+, CD8+, CD16+/- phenotype. In spite of the high frequency of LGL, natural killer (NK) cell activity was absent. Stimulation with interleukin-2 in vitro, however, resulted in high lymphokine-activate d killer (LAK) cell activity against NK-resistant targets. The T-cell nature of the LAK precursor cells is in contrast to the majority seen in normal peripheral blood. Therapeutic trials of cyclosporin A, low-d ose cyclophosphamide, and levamisole were unsuccessful in reducing tra nsfusion requirements. This case is unique in the association of LDGL with celiac disease. It is also unique in that the patient had been fo llowed for several years prior to the onset of the LDGL. The case exte nds the list of lymphoproliferative disorders documented to be associa ted with celiac disease and, conversely, adds to our knowledge of lymp hoproliferative disorder of LGL and its ''dysimmune'' manifestations.