Objective: To estimate the prevalence of protein kinase A type I isozyme (PKA-I) deficiency in a cohort of systemic lupus erythematosus (SLE) patients, and to establish whether the isozyme deficiency is associated with SLE disease activity.
Methods: Thirty-five SLE patients and 35 age-, sex-, and race-matched normal controls were studied. Fifteen subjects were restudied on at least 3 occasions over a 4-year interval. Clinical disease activity was estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and the T cell activation markers CD25+ and HLA-DR+ were quantified by flow cytometry. PKA-I isozyme activities were quantified in enriched T cells. Statistical analyses were performed by Student's t-test, Mann Whitney U test, and Pearson product moment test.
Results: The mean PKA-I activity in SLE T cells (540 pmoles/minute/mg of protein) was significantly lower than that in control T cells (1,578 pmoles/ minute/mg of protein) (P<0.001). The prevalence of isozyme deficiency in this cohort was 80%. During a 4-year interval, PKA-I activities remained significantly reduced, whereas SLEDAI scores significantly improved. There was no relationship between deficient PKA-I activity and either SLEDAI scores or the proportion of T cells bearing CD25+ or HLA-DR+ activation markers.
Conclusion: There is a high prevalence of deficient T cell PKA-I isozyme activity in SLE that persists over time and is independent of SLE disease activity.