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INTRODUCTION: 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. MATERIALS AND 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. RESULTS AND DISCUSSION: 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. CONCLUSION: 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.

Original publication

DOI

10.1007/s10875-010-9429-y

Type

Journal article

Journal

Journal of clinical immunology

Publication Date

09/2010

Volume

30

Pages

649 - 658

Addresses

Peninsula Medical School, University of Exeter and Royal Devon and Exeter Hospital, Exeter, UK. paul.eggleton@pms.ac.uk

Keywords

Lymphocytes, Cells, Cultured, Humans, Arthritis, Rheumatoid, Lupus Erythematosus, Systemic, Gene Expression Profiling, Apoptosis, Gene Expression Regulation, Adult, Aged, Middle Aged, Female, Male, Death Domain Receptor Signaling Adaptor Proteins, CARD Signaling Adaptor Proteins