Successful Renal Transplantation in a Patient with Large Granular Lymphocytic Leukemia with Natural Killer Cell Proliferation

Abstract

A patient with advancing renal failure attributed to focal segmental glomerulosclerosis was found to have marked NK (CD56+) cell expansion and large granular lymphocytic leukemia. Subsequent living-related renal transplantation was accomplished with two early bouts of acute cellular rejection requiring therapy with methylprednisolone and monoclonal antibody OKT3. Chronic triple drug immunosuppressive therapy has substantially reduced the marked NK (CD56+) proliferation. The renal transplantation remains successful after 15 months despite persistent but reduced numbers of circulating NK cells, the potential role of which in the pathogenesis of the underlying nephropathy or the cellular rejection process remains speculative.

Lymphocyte subsets may discern treatment effects in children and young adults with post-transplant lymphoproliferative disorder

“…Since four of these six patients received antilymphocyte therapy, these findings may suggest a treatment effect, characterizing a state of persistent, underlying immunosuppression. This is supported by previous studies in which NK cell reconstitution was delayed or incomplete in transplant recipients treated with OKT3 (9,11). If related to OKT3, however, these observations may be indicative of an indirect effect.…”

“…However, within the expanded CD8 population, we were unable to distinguish EBV‐induced proliferation of cytotoxic CD8 cells from an increase, which may have resulted from the appearance of the CD8+CD57+ phenotype in response to Thymoglobulin. To discern such treatment effects, HLA‐DR expression on CD8 cells, which may be enhanced during EBV infection, and CD57 expression on CD8+ cells, which is enhanced by polyclonal antibody use, may provide invaluable supplementary information (10–12). These additional tests can also be performed by routine multiparametric flow cytometry, under laboratory conditions less rigorous than those required to measure the cytokine response of CD8 cells to autologous, EBV‐primed, antigen‐presenting cells.…”

Spectrum of Kidney Disorders Associated with T-Cell Immunoclones

“…Cytopenia (autoimmune hemolytic anemia and neutropenia) and rheumatoid arthritis are the most frequent immune disorders associated with LGL, but a wide panel of autoimmune diseases were also observed in patients with LGL, including hematological (red cell aplasia, pernicious anemia, thrombocytopenia), neurological (myasthenia gravis, polyradiculoneuropathy), or rheumatic (Sjögren's syndrome, lupus) disorders [1,2]. To date, only seven cases of renal disease related to LGL have been reported, including renal infiltration by the LGL or heterogeneous glomerulopathies (focal and segmental glomerulosclerosis, vasculitis with anti-glomerular basement membrane antibodies, heavy-chain amyloidosis, glomerulonephritis with endocapillary proliferation) [6][7][8][9][10][11][12]. Recently, we reported two cases of inflammatory renal fibrosis associated with a small-sized T-cell clone (i.e., a clonal population not associated with lymphocytosis and thus requiring dedicated immunophenotyping to be identified) [13].…”