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Changes in Apoptotic Gene Expression in Lymphocytes from Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients Compared with Healthy Lymphocytes
Authors:Paul Eggleton  Lorna W. Harries  Giada Alberigo  Paul Wordsworth  Nick Viner  Richard Haigh  Suzanne Donnelly  Hugh W. Jones  Ian C. Chikanza  Thomas W. E. O’Conner  Alasdair E. R. Thomson  Paul G. Winyard
Affiliation:1. Peninsula Medical School, University of Exeter and Royal Devon and Exeter Hospital, Exeter, UK
8. Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Heavitree Rd., Exeter, Devon, EX1 2LU, UK
2. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford, UK
3. Torbay Hospital, Torquay, Devon, UK
4. Mater Misericordiae University Hospital, Dublin, Ireland
5. Kingston Hospital, Surrey, UK
6. St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London, UK
7. St. Thomas’ Hospital, London, UK
Abstract:

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?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.
Keywords:
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