Skip to main content

Advertisement

SpringerLink
Log in

Apoptosis and autoimmunity: Complement deficiency and systemic lupus erythematosus revisited

  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Apoptosis may have a dual role in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus. First, this process may be integral in the clonal deletion of self-reactive lymphocytes and maintenance of peripheral tolerance. Second, apoptosis generates altered self-antigens with the potential for breaking self-tolerance. This review will discuss these two aspects of apoptosis and autoimmunity, and explore the potential role of the classical complement pathway in this context.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Singer GG, Carrera AC, Marshak-Rothstein A, et al.: Apoptosis, Fas and systemic autoimmunity: the MRL-lpr/lpr model. Curr Opin Immunol 1994, 6:913–920.

    Article  PubMed  CAS  Google Scholar 

  2. Goodnow CC: Transgenic mice and analysis of B-cell tolerance. Annu Rev Immunol 1992, 10:489–518.

    Article  PubMed  CAS  Google Scholar 

  3. Ring GH, Lakkis FG: Breakdown of self-tolerance and the pathogenesis of autoimmunity. Semin Nephrol 1999, 19:25–33.

    PubMed  CAS  Google Scholar 

  4. Levine JS, Koh JS: The role of apoptosis in autoimmunity: immunogen, antigen, and accelerant. Semin Nephrol 1999, 19:34–47.

    PubMed  CAS  Google Scholar 

  5. Van Parijs L, Abbas AK: Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science 1998, 280:243–248.

    Article  PubMed  Google Scholar 

  6. Wang J, Lenardo MJ: Molecules involved in cell death and peripheral tolerance. Curr Opin Immunol 1997, 9:818–825.

    Article  PubMed  CAS  Google Scholar 

  7. Itoh N, Yonehara S, Ishii A, et al.: The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 1991, 66:233–243.

    Article  PubMed  CAS  Google Scholar 

  8. Nagata S: Apoptosis by death factor. Cell 1997, 88:355–365.

    Article  PubMed  CAS  Google Scholar 

  9. Nishimura Y, Ishii A, Kobayashi Y, et al.: Expression and function of mouse Fas antigen on immature and mature T cells. J Immunol 1995, 154:4395–4403.

    PubMed  CAS  Google Scholar 

  10. Suda T, Okazaki T, Naito Y, et al.: Expression of the Fas ligand in cells of T-cell lineage. J Immunol 1995, 154:3806–3813.

    PubMed  CAS  Google Scholar 

  11. Dhein J, Walczak H, Baumler C, et al.: Autocrine T-cell suicide mediated by APO-1/ (Fas/ CD95). Nature 1995, 373:438–441.

    Article  PubMed  CAS  Google Scholar 

  12. Brunner T, Mogil RJ, LaFace D, et al.: Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature 1995, 373:441–444.

    Article  PubMed  CAS  Google Scholar 

  13. Ju S, Panka DJ, Cui H, et al.: Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature 1995, 373:444–448.

    Article  PubMed  CAS  Google Scholar 

  14. Rothstein TL, Wang JKM, Panka DJ, et al.: Protection against Fas-dependent Th1-mediated apoptosis by antigen receptor engagement in B cells. Nature 1995, 374:163–165.

    Article  PubMed  CAS  Google Scholar 

  15. Watanabe-Fukunaga R, Brannan CI, et al.: Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptotis. Nature 1992, 356:314–317.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  17. Foster MH: Relevance of systemic lupus erythematosus nephritis animal models to human disease. Semin Nephrol 1999, 19:12–24.

    PubMed  CAS  Google Scholar 

  18. Weston KM, Ju S, Lu CY, Sy M: Autoreactive T cells in MRL/ MP-LPR/LPR mice: characterization of the lymphokines produced and analysis of antigen-presenting cells required. J Immunol 1988, 141:1941–1948.

    PubMed  CAS  Google Scholar 

  19. Russell JH, Rush B, Weaver C, Wang R: Mature T cells of autoimmune lpr/lpr mice have a defect in antigen-stimulated suicide. Proc Natl Acad Sci USA 1993, 90:4409–4413.

    Article  PubMed  CAS  Google Scholar 

  20. Bossu P, Singer GG, Andres P, et al.: Mature CD4+ T lymphocytes from MRL/lpr mice are resistant to receptor-mediated tolerance and apoptosis. J Immunol 1993, 151:7233–7239.

    PubMed  CAS  Google Scholar 

  21. Rieux-Laucat F, Le Deist F, Hivroz C, et al.: Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science 1995, 268:1347–1349.

    Article  PubMed  CAS  Google Scholar 

  22. Fisher GH, Rosenberg FJ, Straus SE, et al.: Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 1995, 81:935–946.

    Article  PubMed  CAS  Google Scholar 

  23. Drappa J, Vaishnaw AK, Sullivan KE, et al.: Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity. N Eng J Med 1996, 335:1643–1649.

    Article  CAS  Google Scholar 

  24. Wu J, Wilson J, He J, et al.: Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease. J Clin Invest 1996, 98:1107–1113.

    Article  PubMed  CAS  Google Scholar 

  25. Straus SE, Sneller M, Lenardo MJ, et al.: An inherited disorder of lymphocyte apoptosis: the autoimmune lymphoproliferative syndrome. Ann Intern Med 1999, 130:591–601.

    PubMed  CAS  Google Scholar 

  26. Wang J, Zheng L, Lobito A, et al.: Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome Type II. Cell 1999, 98:47–58. Researchers examined two families with ALPS Type II autoimmunity with apoptosis defects, but no mutations in Fas, FasL, TNFR1, TNFR2, FADD, or CASP8. Single-stranded conformational polymorphism analysis and cDNA sequencing identified a mutation in CASP10 that results in decreased caspase activity and interferes with Fas ligand and TRAIL-induced apoptosis.

    Article  PubMed  CAS  Google Scholar 

  27. Casciola-Rosen LA, Anhalt G, Rosen A: Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med 1994, 179:1317–1330.

    Article  PubMed  CAS  Google Scholar 

  28. Miranda ME, Tseng C, Rashbaum W, et al.: Accessibility of SSA/Ro and SSB/La antigens to maternal autoantibodies in apoptotic human fetal cardiac myocytes. J Immunol 1998, 161:5061–5069. These researchers demonstrated that the autoantigens Ro and La become accessible to autoantibodies in blebs on the surface of apoptotic cardiac myocytes. These findings confirm that autoantigens become relocated as a result of apoptosis and suggest that autoantibodies may be directly responsible for tissue injury.

    PubMed  CAS  Google Scholar 

  29. Casciola-Rosen LA, Miller DK, Anhalt GJ, Rosen A: Specific cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death. J Biol Chem 1994, 269:30757–30760.

    PubMed  CAS  Google Scholar 

  30. Casciola-Rosen LA, Anhalt GJ, Rosen A: DNA-dependent protein kinase is one of a subset of autoantigens specifically cleaved early during apoptosis. J Exp Med 1995, 182:1625–1634.

    Article  PubMed  CAS  Google Scholar 

  31. Casciola-Rosen LA, Nicholson DW, Chong T, et al.: Apopain/ CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death. J Exp Med 1996, 183:1957–1964.

    Article  PubMed  CAS  Google Scholar 

  32. Casiano CA, Martin SJ, Green DR, Tan EM: Selective cleavage of nuclear autoantigens during CD95 (Fas/APO-1)-mediated T cell apoptosis. J Exp Med 1996, 184:765–770.

    Article  PubMed  CAS  Google Scholar 

  33. Utz PJ, Hottelet M, Le TM, et al.: The 72-kDa component of signal recognition particle is cleaved during apoptosis. J Biol Chem 1998, 273:35362–35370. An autoantigen targeted by patients with dermatomyositis and SLE, a signal recognition particle, is cleaved and phosphorylated during apoptosis.

    Article  PubMed  CAS  Google Scholar 

  34. Utz PJ, Hottelet M, Schur PH, Anderson P: Proteins phosphorylated during stress-induced apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus. J Exp Med 1997, 185:843–854. Sera from patients with SLE were found to recognize proteins that are phosphorylated during apoptosis. This study provides evidence that apoptosis-induced phosphorylation may be a way that self-antigens are altered and recognized in autoimmunity.

    Article  PubMed  CAS  Google Scholar 

  35. Andrade F, Roy S, Nicholson D, et al.: Granzyme B directly and efficiently cleaves several downstream caspase substrates: implications for CTL-induced apoptosis. Immunity 1998, 8:451–460. Caspases are a family of cysteine proteases involved in mediating apoptosis, and many caspase substrates are human autoantigens. This study demonstrates that granzyme B can mediate caspaseindependent apoptosis. Of interest is that granzyme-B substrates are also autoantigens, and granzyme-B cleavage generates fragments that are unique compared with those generated during any other form of apoptosis. This suggests that CTL-induced apoptosis may generate novel fragments of autoantigens.

    Article  PubMed  CAS  Google Scholar 

  36. Rosen A, Casciola-Rosen L, Ahearn J: Novel packages of viral and self-antigens are generated during apoptosis. J Exp Med 1995, 181:1557–1561.

    Article  PubMed  CAS  Google Scholar 

  37. Albert ML, Sauter B, Bhardwaj N: Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998, 392:86–89. Influenza infection of macrophages induces apoptosis. Dendritic cells exposed to apoptotic influenza-infected monocytes acquire antigen and can prime virus-specific CTL. This study demonstrates that apoptotic bodies are immunogenic.

    Article  PubMed  CAS  Google Scholar 

  38. Albert ML, Pearce SFA, Francisco LM, et al.: Immature dendritic cells phagocytose apoptotic cells via aVb5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 1998, 188:1359–1368. This study demonstrates that "immature" dendritic cells (DC), (CD14-/ CD83-), but not "mature" (CD14-/CD83+) DC phagocytize apoptotic bodies, can prime CTL. Of particular interest is the demonstration that CD36 coupled with aVb5 mediates this phagocytosis in DC.

    Article  PubMed  CAS  Google Scholar 

  39. Rovere P, Sabbadini MG, Vallinoto C, et al.: Delayed clearance of apoptotic lymphoma cells allows cross-presentation of intracellular antigens by mature dendritic cells. J Leuk Biol 1999, 66:345–349.

    CAS  Google Scholar 

  40. Bartholeyns J, Romet-Lemonne JL, Chokri M, et al.: Cellular vaccines. Res Immunol 1998, 149:647–649.

    Article  PubMed  CAS  Google Scholar 

  41. Henry F, Boisteau O, Bretaudeau L, et al.: Antigen-presenting cells that phagocytose apoptotic tumor-derived cells are potent tumor vaccines. Cancer Res 1999, 59:3329–3332.

    PubMed  CAS  Google Scholar 

  42. Mevorach D, Zhou JL, Song X, Elkon KB: Systemic exposure to irradiated apoptotic cells induces autoantibody production. J Exp Med 1998, 188:387–392.

    Article  PubMed  CAS  Google Scholar 

  43. Davies KA, Schifferli JA, Walport MJ: Complement deficiency and immune complex disease. Springer Sem Immunopath 1994, 15:397–416.

    Article  CAS  Google Scholar 

  44. Walport MJ, Davies KA, Morley BJ, Botto M: Complement deficiency and autoimmunity. Ann NY Acad Sci 1997, 815:267–281.

    Article  PubMed  CAS  Google Scholar 

  45. Walport MJ, Davies KA, Botto M: C1q deficiencies and C1q in autoimmunity. Immunobiology 1998, 199:265–285.

    PubMed  CAS  Google Scholar 

  46. Navratil JS, Korb LC, Ahearn JM: Systemic lupus erythematosus and complement deficiency: clues to a novel role for the classical complement pathway in the maintenance of immune tolerance. Immunopharmacology 1999, 42:47–52.

    Article  PubMed  CAS  Google Scholar 

  47. Korb LC, Ahearn JM: C1q binds directly and specifically to surface blebs of apoptotic human keratinocytes: complement deficiency and systemic lupus erythematosus revisited. J Immunol 1997, 158:4525–4528. This study demonstrated that the first component of the classical complement system, C1q, binds to surface blebs on human keratinocytes rendered apoptotic by ultraviolet-B irradiation or Sindbis virus infection. This binding occurs in the absence of immunoglobulin, and may represent a novel role for the classical complement pathway in recognition of apoptotic cells.

    PubMed  CAS  Google Scholar 

  48. Navratil JS, Wisnieski JJ, Ahearn JM: The globular heads of C1q bind specifically to the surface blebs of apoptotic human endothelial cells: implications for immune tolerance. Mol Immunol 1998, 35:398.

    Article  Google Scholar 

  49. Botto M, Dell’Agnola C, Bygrave AE, et al.: Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 1998, 19:56–59. These researchers generated C1q-deficient mice by targeted disruption of the first exon of the C1qa gene. Mice with this homozygous mutation on a mixed genetic background (129/OlaXC57BL/6) develop high titers of antinuclear antibodies and glomerulonephritis. Of particular interest is the observation that there were significantly higher numbers of apoptotic bodies in the glomeruli of the C1q-deficient mice as compared with normal controls, even when glomerulonephritis was absent. This suggests that C1q-deficiency is associated with impaired clearance of apoptotic cells.

    Article  PubMed  CAS  Google Scholar 

  50. Taylor PR, Nash JT, Theodoridis E, et al.: A targeted disruption of the murine complement factor B gene resulting in loss of expression of three genes in close proximity, factor B, C2, and D17H6S45. J Biol Chem 1998, 273:1699–1704.

    Article  PubMed  CAS  Google Scholar 

  51. Mitchell DA, Taylor PR, Cook HT, et al.: C1q protects against the development of glomerulonephritis independently of C3 activation. J Immunol 1999, 162:5676–5679. Mice deficient in both C2 and factor B, and thereby unable to activate C3 by either the classical or alternative pathway of complement, (H2-Bf/C2-/-) were developed through gene-targeting, and crossed with mice with homozygous C1q deficiency. Unlike mice with homozygous C1q deficiency, H2-Bf/C2-/-mice do not develop glomerulonephritis or antinuclear antibodies, unless they are also deficient in C1q. These data suggest that C3 deposition is not necessary for the development of glomerulonephritis. Of interest is the fact that C2 and factor-B deficiency is not associated with accumulation of apoptotic bodies unless coupled with C1q deficiency, suggesting that C1q but not C3 may be involved in clearance of apoptotic cells.

    PubMed  CAS  Google Scholar 

  52. Cseh PG, Schumaker VN, Zavodszky P: The structure and function of the first component of complement: genetic engineering approach. Acta Microbiol Immunol Hungarica 1994, 41:361–380.

    Google Scholar 

  53. Reid KB, Porter RR: Subunit composition and structure of subcomponent C1q of the first component of human complement. Biochem J 1976, 155:19–23.

    PubMed  CAS  Google Scholar 

  54. Ghebrehiwet B, Lim B, Peerschke EIB, et al.: Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q. J Exp Med 1994, 179:1809–1821.

    Article  PubMed  CAS  Google Scholar 

  55. Ghebrehiwet B, Kew RR, Gruber BL, et al.: Murine mast cells express two types of C1q receptors that are involved in the induction of chemotaxis and chemokinesis. J Immunol 1995, 155:2614–2619.

    PubMed  CAS  Google Scholar 

  56. Peerschke EIB, Smyth SS, Teng EI, et al.: Human umbilical vein endothelial cells possess binding sites for the globular domain of C1q. J Immunol 1996, 157:4154–4158.

    PubMed  CAS  Google Scholar 

  57. Nepomuceno RR, Henschen-Edman AH, Burgess WH, Tenner AJ: cDNA cloning and primary structure analysis of C1qRP, the human C1q/MBL/SPA receptor that mediates enhanced phagocytosis in vitro. Immunity 1997, 6:119–129. The receptor that has been shown to enhance phagocytosis in the presence of C1q (C1qRP) was cloned and the amino acid sequence analyzed. This receptor has homology with other cell surface proteins that modulate endocytosis, and has all the necessary molecular components for signal transduction.

    Article  PubMed  CAS  Google Scholar 

  58. Nepomuceno RR, Tenner AJ: C1qRP, the C1q receptor that enhances phagocytosis, is detected specifically in human cells of myeloid lineage, endothelial cells, and platelets. J Immunol 1998, 160:1929–1935. Expression of the C1q phagocytic receptor C1qRP was assessed on primary human cells and cell lines by RT PCR and by FACS analysis. C1qRP is expressed in endothelial cells, cells of myeloid origin, and platelets, but not on lymphocytes, epithelial cells, or fibroblasts.

    PubMed  CAS  Google Scholar 

  59. Klickstein LB, Barbashov SF, Liu T, et al.: Complement receptor type I (CR1, CD35) is a receptor for C1q. Immunity 1997, 7:345–355. This study demonstrated that the collagen-like tail region of C1q binds to CR1. This suggests that CR1 may be a receptor for C1q, although functional consequences of C1q-CR1 interactions are not shown.

    Article  PubMed  CAS  Google Scholar 

  60. Tenner AJ: C1q receptors: regulating specific function of phagocytic cells. Immunobiol 1998, 199:250–264.

    CAS  Google Scholar 

  61. Guan E, Robinson SL, Goodman EB, Tenner AJ: Cell-surface protein identified on phagocytic cells modulates the C1q-mediated enhancement of phagocytosis. J Immunol 1994, 152:4005–4016.

    PubMed  CAS  Google Scholar 

  62. Butko P, Nicholson-Weller A, Wessels MR: Role of complement component C1q in the IgG-independent opsonophagocytosis of group B streptococcus. J Immunol 1999, 163:2761–2768. This study investigated the role that C1q plays in immunoglobulinfree opsonization of group-B streptococcus(GBS). C1q binds directly to GBS via its globular heads, and enhances phagocytic killing of these bacteria. These researchers found that C1q alone is not responsble for the opsonophagocytosis; however, other serum factors are required, possibly other components of the classical complement pathway.

    PubMed  CAS  Google Scholar 

  63. Navratil JS, Wisnieski JJ, Ahearn JM: Apoptotic primary cells specifically activate the classical complement pathway: implications for immune tolerance and the pathogenesis of SLE. Arthritis Rheum 1999, 42(Suppl):S406.

    Article  Google Scholar 

  64. Tas SW, Klickstein LB, Barbashov SF, Nicholson-Weller A: C1q and C4b bind simultaneously to CR1 and additively support erythrocyte adhesion. J Immunol 1999, 163:5056–5063. This study demonstrated that C1q and C4b cooperate in binding to CR1 on erythrocytes. The presence of both C1q and C4b on particles enhances CR1 binding as compared with either ligand alone. These data suggest that C1q and C4b may act together in immune complex clearance, and may have implications for other CR1 interactions as well.

    PubMed  CAS  Google Scholar 

  65. Ahearn JM, Rosengard AM: Complement Receptors. In The Human Complement System in Health and Disease. Edited by Volanakis JE, Frank MM. New York: Marcel Dekker, Inc; 1998:167–202.

    Google Scholar 

  66. Savill JS, Wyllie AH, Henson JE, et al.: Macrophage phagocytosis of aging neutrophils in inflammation: programmed cell death in the neutrophil leads to its recognition in macrophages. J Clin Invest 1989, 83:865–875.

    Article  PubMed  CAS  Google Scholar 

  67. Savill J, Fakok V, Henson P, Haslett C: Phagocyte recognition of cells undergoing apoptosis. Immunol Today 1993, 14:131–136.

    Article  PubMed  CAS  Google Scholar 

  68. Fadok VA, Bratton DL, Konowal A, et al.: Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-b, PGE2, and PAF. J Clin Invest 1998, 101:890–898. Phagocytosis of apoptotic neutrophils by macrophages induces production of transforming growth factor-b1, prostaglandin E2, and platelet-activating factor, which in turn inhibit proinflammatory cytokine production by macrophages. This study provides evidence that clearance of apoptotic cells is a noninflammatory process.

    Article  PubMed  CAS  Google Scholar 

  69. Hughes J, Liu Y, Van Damme J, Savill J: Human glomerular mesangial cell phagocytosis of apoptotic neutrophils: mediation by a novel CD36-independent vitronectin receptor/ thrombospondin recognition mechanism that is uncoupled from chemokine secretion. J Immunol 1997, 158:4389–4397. This study demonstrated that cultured glomerular mesangial cells utilize the aVb3 vitronectin receptor independently of CD36 in the phagocytosis of apoptotic neutrophils.

    PubMed  CAS  Google Scholar 

  70. Dini L, Lentini A, Diez G, et al.: Phagocytosis of apoptotic bodies by liver endothelial cells. J Cell Science 1995, 108:967–973.

    PubMed  CAS  Google Scholar 

  71. Rubartelli A, Poggi A, Zocchi MR: The selective engulfment of apoptotic bodies by dendritic cells is mediated by the aVb3 integrin and requires intracellular and extracellular calcium. Eur J Immunol 1997, 27:1893–1900.

    Article  PubMed  CAS  Google Scholar 

  72. Fadok VA, Warner ML, Bratton DL, Henson PM: CD36 is required for phagocytosis of apoptotic cells by human macrophages that use either a phosphatidylserine receptor or the vitronectin receptor (aVb3). J Immunol 1998, 161:6250–6257.

    PubMed  CAS  Google Scholar 

  73. Devitt A, Moffatt OD, Raykundalia C, et al.: Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 1998, 392:505–509. Macrophages utilize CD14 as a receptor that triggers phagocytosis of apoptotic cells. Although CD14 is also a receptor for bacterial lipopolysaccharide (LPS), and LPS-induced phagocytosis triggers inflammatory response, CD14-induced phagocytosis of apoptotic cells is noninflammatory.

    Article  PubMed  CAS  Google Scholar 

  74. Mevorach D, Mascarenhas JO, Gershov D, Elkon KB: Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 1998, 188:2313–2320.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Pittsburgh School of Medicine, University of Pittsburgh Arthritis Institute, E1152 Biomedical Science Tower, 200 South Lothrop Street, 15261, Pittsburgh, PA, USA

    Jeannine S. Navratil MS & Joseph M. Ahearn MD

Authors
  1. Jeannine S. Navratil MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph M. Ahearn MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Navratil, J.S., Ahearn, J.M. Apoptosis and autoimmunity: Complement deficiency and systemic lupus erythematosus revisited. Curr Rheumatol Rep 2, 32–38 (2000). https://doi.org/10.1007/s11926-996-0066-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-996-0066-7

Keywords

Search

Navigation