Changes in apoptotic gene expression in lymphocytes from rheumatoid arthritis and systemic lupus erythematosus patients compared with healthy lymphocytes.
BACKGROUND
Systemic lupus erythematosus (SLE) and rheumatoid arthritis have complex genetic traits, but in both autoimmune diseases, dysfunctional apoptosis appears to play a part in disease pathology. This study examined the levels of in vitro apoptosis in lymphocytes from healthy, rheumatoid arthritis (RA) and SLE individuals and related observed differences to their lymphocyte apoptosis gene profiles.


METHODS
Lymphocytes were assessed for cell death by nuclear pyknosis and DNA fragmentation. Control, SLE and RA apoptosis gene profiles were obtained by quantitative real-time polymerase chain reaction (QRT-PCR) analysis.


CONCLUSIONS
The mean levels of pyknosis in RA and SLE freshly isolated lymphocytes were significantly higher than in control lymphocytes. Ninety-three apoptosis genes were analysed by QRT-PCR of mRNA from RA, SLE and healthy lymphocytes. We identified significant differences (p < 0.05) in the expression of the same 11 of 93 and two of 93 apoptotic genes in individual SLE and RA patients tested as compared with controls.


CONCLUSIONS
We propose that similarly altered expression of specific apoptotic regulatory genes (e.g., the death effector domain-containing DNA-binding protein and apoptosis-associated speck-like protein containing a CARD) occurs in the lymphocytes of individual patients with SLE or RA that may influence the extent and rate of spontaneous apoptosis in these autoimmune conditions.
Peninsula Medical School, University of Exeter and Royal Devon and Exeter Hospital, Exeter, UK. paul.eggleton@pms.ac.uk
Paul
P
Eggleton
Lorna W
LW
Harries
Giada
G
Alberigo
Paul
P
Wordsworth
Nick
N
Viner
Richard
R
Haigh
Suzanne
S
Donnelly
Hugh W
HW
Jones
Ian C
IC
Chikanza
Thomas W E
TW
O'Conner
Alasdair E R
AE
Thomson
Paul G
PG
Winyard
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged
D053468:CARD Signaling Adaptor Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins