Skip to main content
Log in

Lymphocyte apoptosis and macrophage function: correlation with disease activity in systemic lupus erythematosus

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Increased lymphocyte apoptosis and defects in macrophage removal of apoptotic cells have been suggested to contribute to the development of systemic lupus erythematosus (SLE). The aim of this study was to investigate the relationship between peripheral lymphocyte apoptosis, macrophage function as determined by the serum levels of neopterin and interferon-γ (IFN-γ), and SLE disease activity. Peripheral apoptotic lymphocytes (AL) were detected by annexin V-fluorescein isothiocyanate (FITC) staining and flow cytometry. Serum levels of neopterin and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA). SLE disease activity was determined using the systemic lupus activity measure (SLAM) and the serum titer of anti-dsDNA antibodies. The percentage of AL in the peripheral blood of active SLE patients was significantly higher (13.07±7.39%, n=30) than that of the inactive SLE patients (4.08±3.55%, n=8, p<0.01) and normal controls (5.13±3.37%, n=11, p<0.01). Serum levels of neopterin in active SLE patients were significantly higher (1.39±1.10 μg/dl, n=22) than in controls (0.26±0.19 μg/dl, n=20, p<0.01). Serum levels of IFN-γ in active SLE patients were elevated (58.97±34.52 ng/l, n=15) when compared with controls (28.06±2.35 ng/l, n=16, p<0.05). The percentage of AL correlated significantly with serum levels of neopterin (r=0.446, p<0.05, n=22) and SLAM score (r=0.533, p<0.001, n=38), but not with the serum levels of IFN-γ. The SLAM score also correlated with the serum levels of neopterin (r=0.485, p<0.05, n=22), but not with those of IFN-γ. Our study supported the hypothesis that increased lymphocyte apoptosis has a pathogenic role in SLE. The increased levels of serum neopterin may suggest an attempt of the patients’ macrophage system to remove the apoptotic cell excess. Since serum levels of neopterin correlated with the overall lupus disease activity, they may be regarded as an index of SLE disease activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Emlen W, Niebur J, Kadera R (1994) Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus. J Immunol 152:3685–3693

    CAS  PubMed  Google Scholar 

  2. Perniok A, Wedekind F, Herrmann M, Specker C, Schneider M (1998) High levels of circulating early apoptotic peripheral blood mononuclear cells in systemic lupus erythematosus. Lupus 7:113–118

    Article  CAS  PubMed  Google Scholar 

  3. Courtney PA, Crockard AD, Williamson K, Irvine AE, Kennedy RJ, Bell AL (1999) Increased apoptotic peripheral blood neutrophils in systemic lupus erythematosus: relations with disease activity, antibodies to double stranded DNA, and neutropenia. Ann Rheum Dis 58:309–314

    CAS  PubMed  Google Scholar 

  4. Herrmann M, Voll RE, Zoller OM, Hagenhofer M, Ponner BB, Kalden JR (1998) Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum 41:1241–1250

    Article  CAS  PubMed  Google Scholar 

  5. Baumann I, Kolowos W, Voll RE, et al. (2002) Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum 46:191–201

    Article  PubMed  Google Scholar 

  6. Lorenz HM, Herrmann M, Winkler T, Gaipl U, Kalden JR (2000) Role of apoptosis in autoimmunity. Apoptosis 5:443–449

    Article  CAS  PubMed  Google Scholar 

  7. Taylor PR, Carugati A, Fadok VA, et al. (2000) A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 192:359–366

    Article  CAS  PubMed  Google Scholar 

  8. Ren Y, Tang J, Mok MY, Chan AW, Wu A, Lau CS (2003) Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus. Arthritis Rheum 48:2888–2897

    Article  PubMed  Google Scholar 

  9. Huber C, Batchelor JR, Fuchs D, et al. (1984) Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma. J Exp Med 160:310–316

    Article  CAS  PubMed  Google Scholar 

  10. Berdowska A, Zwirska-Korczala K (2001) Neopterin measurement in clinical diagnosis. J Clin Pharm Ther 26:319–329

    Article  CAS  PubMed  Google Scholar 

  11. Le Page C, Genin P, Baines MG, Hiscott J. Hiscott J (2000) Interferon activation and innate immunity. Rev Immunogenet 2:374–386

    PubMed  Google Scholar 

  12. Liang MH, Socher SA, Larson MG, Schur PH (1989) Reliability and validity of six systems for the clinical assessment of six systems of disease activity in systemic lupus erythematosus. Arthritis Rheum 32:1107–1118

    CAS  PubMed  Google Scholar 

  13. Navratil JS, Ahearn JM (2001) Apoptosis clearance mechanisms, and the development of systemic lupus erythematosus. Curr Rheumatol Rep 3:191–198

    CAS  PubMed  Google Scholar 

  14. Herrmann M, Zoller OM, Hagenhofer M, Voll R, Kalden JR (1996) What triggers anti-dsDNA antibodies? Mol Biol Rep 23:265–267

    CAS  PubMed  Google Scholar 

  15. Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S (1992) Lymphoproliferative disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314–317

    Article  CAS  PubMed  Google Scholar 

  16. Takahashi T, Tanaka M, Brannan C, et al. (1994) Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76:969–976

    Article  CAS  PubMed  Google Scholar 

  17. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    CAS  PubMed  Google Scholar 

  18. Bright J, Khar A (1994) Apoptosis: programmed cell death in health and disease. Biosci Rep 14:67–81

    CAS  PubMed  Google Scholar 

  19. Loo DT, Rillema JR (1998) Measurement of cell death. Methods Cell Biol 57:251–264

    CAS  PubMed  Google Scholar 

  20. Casciola-Rosen LA, Anhalt G, Rosen A (1994) Autoantigens targeted in SLE are clustered in two populations surface structures on apoptotic keratinocytes. J Exp Med 179:1317–1330

    Article  CAS  PubMed  Google Scholar 

  21. Huggins ML, Todd I, Cavers MA, Pavuluri SR, Tighe PJ, Powell RJ (1999) Antibodies from systemic lupus erythematosus (SLE) sera define differential release of autoantigens from cell lines undergoing apoptosis. Clin Exp Immunol 118:322–328

    Article  CAS  PubMed  Google Scholar 

  22. Licht R, Jacobs CW, Tax WJ, Berden JH (2001) No constitutive defect in phagocytosis of apoptotic cells by resident peritoneal macrophages from pre-morbid lupus mice. Lupus 10:102–107

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chak-sing Lau.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jin, O., Sun, Ly., Zhou, Kx. et al. Lymphocyte apoptosis and macrophage function: correlation with disease activity in systemic lupus erythematosus. Clin Rheumatol 24, 107–110 (2005). https://doi.org/10.1007/s10067-004-0972-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-004-0972-x

Keywords

Navigation