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Changes in Apoptotic Gene Expression in Lymphocytes from Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients Compared with Healthy Lymphocytes

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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 < 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.

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Acknowledgements

We thank Dr Alicja M Gruska for help with the slide assays, Dr Claire Bennett (Exeter University, UK) for help in optimising the TLDA-QRT-PCR method and Dr Vanessa Gilston for technical assistance. We also thank Mrs Susan Westoby for secretarial assistance and Dr Marc Williams (University of Rochester School of Medicine and Dentistry) for critical review of the manuscript. This work was supported by research grants from the Arthritis Research Campaign numbers, E0521, E0543, 17231, and 16537 and Lupus UK. Support was also received from the Peninsula NIHR Clinical Research facility. We dedicate this paper to the memory of our colleague Dr Gilmour Harris, a provocative and admired immunologist, who played a central role in initiating the study reported here.

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The authors have no conflict of interest.

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Authors and Affiliations

  1. Peninsula Medical School, University of Exeter and Royal Devon and Exeter Hospital, Exeter, UK

    Paul Eggleton, Lorna W. Harries, Giada Alberigo, Richard Haigh & Paul G. Winyard

  2. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford, UK

    Paul Wordsworth

  3. Torbay Hospital, Torquay, Devon, UK

    Nick Viner

  4. Mater Misericordiae University Hospital, Dublin, Ireland

    Suzanne Donnelly

  5. Kingston Hospital, Surrey, UK

    Hugh W. Jones

  6. St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London, UK

    Ian C. Chikanza

  7. St. Thomas’ Hospital, London, UK

    Thomas W. E. O’Conner & Alasdair E. R. Thomson

  8. Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Heavitree Rd., Exeter, Devon, EX1 2LU, UK

    Paul Eggleton

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  1. Paul Eggleton
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Correspondence to Paul Eggleton.

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Eggleton, P., Harries, L.W., Alberigo, G. et al. Changes in Apoptotic Gene Expression in Lymphocytes from Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients Compared with Healthy Lymphocytes. J Clin Immunol 30, 649–658 (2010). https://doi.org/10.1007/s10875-010-9429-y

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  • DOI: https://doi.org/10.1007/s10875-010-9429-y

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