Decreased DAP12 expression in natural killer lymphocytes from patients with systemic lupus erythematosus is associated with increased transcript mutations

Decreased numbers of natural killer (NK) cells and impaired NK function have been reported in patients with systemic lupus erythematosus (SLE). Since DAP12 plays a pivotal role in activation of NK cells, we analyzed the expressions of DAP12 protein and mRNA in peripheral blood NK cells from patients with SLE. Both DAP12 protein and mRNA expressions in NK cells from the SLE patients were decreased compared with those in NK cells from normal subjects. Sequence analysis of DAP12 cDNA showed increased nucleotide mutations, including both nucleotide substitutions and deletions. In spite of the mRNA mutations, we found no mutations in genomic DNA, suggesting that mRNA was modified during or after transcription. Decreased expression of DAP12 in NK cells from the patients was accompanied by increased expression of ADAR1 (adenosine deaminase that acts on RNA transcripts) and by decreased expression of NKp44. These results suggest that abnormal expression of DAP12 molecules in NK cells may account for the impairment of NK cell function in patients with SLE.