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and RIß Transcripts and Proteins in Systemic Lupus Erythematosus T Lymphocytes1
*
Section on Rheumatology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157; and
Institute of Medical Biochemistry, University of Oslo, Oslo, Norway
Deficient type I protein kinase A phosphotransferase activity
occurs in the T cells of 80% of subjects with systemic lupus
erythematosus (SLE). To investigate the mechanism of this deficient
isozyme activity, we hypothesized that reduced amounts of type I
regulatory (RI) isoform transcripts, RI
and RIß, may be associated
with a diminution of RI and/or RIß protein. Sixteen SLE subjects
with a mean (±1 SD) SLE disease activity index of 12.4 ± 7.2
were studied. Controls included 16 normal subjects, six subjects with
primary Sjögren’s syndrome (SS), and three subjects with SS/SLE
overlap. RT-PCR revealed that normal, SS, SS/SLE, and SLE T cells
expressed mRNAs for all seven R and catalytic (C) subunit isoforms.
Quantification of mRNAs by competitive PCR revealed that the ratio of
RI mRNA to RIß mRNA in normal T cells was 3.4:1. In SLE T cells
there were 20 and 49% decreases in RI and RIß mRNAs (RIß;
p = 0.008), respectively, resulting in an
RI:RIß mRNA of 5.3:1. SS/SLE T cells showed a 72.5% decrease in
RIß mRNA compared with normal controls (p =
0.01). Immunoblotting of normal T cell RI and RIß proteins
revealed a ratio of RI:RIß of 3.2:1. In SLE T cells, there was a
30% decrease in RI protein (p = 0.002) and a
65% decrease in RIß protein (p < 0.001),
shifting the ratio of RI:RIß protein to 6.5:1. T cells from 25%
of SLE subjects lacked any detectable RIß protein. Analysis of
several lupus T cell lines demonstrated a persistent deficiency of both
proteins, excluding a potential effect of disease activity. In
conclusion, reduced expression of RI and RIß transcripts is
associated with a decrement in RI and RIß proteins and may
contribute to deficient type I protein kinase A isozyme activity in SLE
T cells.
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