Abstract
Defects of hematopoietic stem cells (HSCs) have been suggested to contribute to the development of systemic lupus erythematosus (SLE). The aim of this study was to investigate the phenotypic characteristics of bone marrow (BM) CD34+ cells in patients with SLE and its relationship with SLE disease activity. Ten SLE patients and 10 healthy subjects were recruited and their BM CD34+ cells were analyzed by flow cytometric analysis with CD45/SSC gating for the expression of CD90, CD95, CD117, CD123, CD164, CD166, FAS-L, and HLA-DR. The percentage of BM CD34+ cells was significantly decreased in active SLE patients (1.48 ± 0.41%, n = 7) compared to the healthy controls (2.31 ± 0.75%, n = 10, p < 0.01), but no significant difference was found between the inactive patients (2.04 ± 0.44%, n = 3) and the controls. The expression of CD95, CD123, and CD166 on BM CD34+ cells were significantly increased in SLE patients (48.31 ± 10.59%, 44.9 ± 21.5%, 30.9 ± 19.54%, respectively, n = 10) when compared with the control subjects (24.33 ± 11.1%, 19.5 ± 4.4%, 10.7 ± 5.5%, respectively, n = 10, p < 0.05). The increased CD123 expression was negatively correlated with the number of peripheral white blood cells (r = −0.700, p < 0.05, n = 10). The percentage of CD166 expression was found significantly correlated with the index of SLE disease activity (r = 0.472, p < 0.05, n = 10) and 24 h proteinuria (r = 0.558, p < 0.05, n = 10), but negatively correlated with serum C3 level (r = −0.712, p < 0.01, n = 10). Our study found that the surface marker expression of CD95, CD123, and CD166 on BM CD34+ cells were significantly increased in patients. This supports the hypothesis that there are abnormalities of the HSC in SLE. Since CD166 and CD123 correlated with the overall lupus activity, their role as a biomarker of inflammatory disease activity also requires further study.
Similar content being viewed by others
References
Borchers AT, Keen CL, Shoenfeld Y et al (2004) Surviving the butterfly and the wolf: mortality trends in systemic lupus erythematosus. Autoimmun Rev 3:423–453
Burt RK, Marmont A, Arnold R et al (2003) Development of a phase III trial of hematopoietic stem cell transplantation for systemic lupus erythematosus. Bone Marrow Transplant 32:S49–S51
Nakamura T, Ikehara S, Good RA et al (1985) Abnormal stem cells in autoimmune-prone mice are responsible for premature thymic involution. Thymus 7:151–160
Ikehara S, Kawamura M, Takao F et al (1990) Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells. Proc Natl Acad Sci USA 87:8341–8344
Papadaki HA, Boumpas DT, Gibson FM et al (2001) Increased apoptosis of bone marrow CD34(+) cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus. Br J Haematol 115:167–174
Jones RJ, Wagner JE, Celano P et al (1990) Separation of pluripotent haematopoietic stem cells from spleen colony-forming cells. Nature 347:188–189
Storms RW, Trujillo AP, Springer JB et al (1999) Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc Natl Acad Sci USA 96:9118–9123
Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725
Bombardier C, Gladman DD, Urowitz MB et al (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum 35:630–640
Sovalat H, Racadot E, Ojeda M et al (2003) CD34+ cells and CD34+CD38− subset from mobilized blood show different patterns of adhesion molecules compared to those from steady-state blood, bone marrow, and cord blood. J Hematother Stem Cell Res 12:473–489
Alaez C, Loyola M, Murguia A et al (2005) Hematopoietic stem cell transplantation (HSCT): an approach to autoimmunity. Autoimmun Rev 5:167–179
Tiefenthaler M, Bacher N, Linert H et al (2003) Apoptosis of CD34+ cells after incubation with sera of leukopenic patients with systemic lupus erythematosus. Lupus 12:471–478
Rusten LS, Jacobsen SE (1995) Tumor necrosis factor (TNF)-alpha directly inhibits human erythropoiesis in vitro: role of p55 and p75 TNF receptors. Blood 85:989–996
Hara T, Miyajima A (1996) Function and signal transduction mediated by the interleukin 3 receptor system in hematopoiesis. Stem Cells 14:605–618
Jordan CT, Upchurch D, Szilvassy SJ et al (2000) The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia 1410:1777–1784
Testa U, Riccioni R, Diverio D et al (2004) Interleukin-3 receptor in acute leukemia. Leukemia 18:219–226
Dallera MC, Cardarelli PM, Preston BT et al (2005) Type I interferon correlates with serological and clinical manifestations of SLE. Ann Rheum Dis 64:1692–1697
Ohneda O, Ohneda K, Arai F et al (2001) ALCAM (CD166): its role in hematopoietic and endothelial development. Blood 98:2134–2142
Kato Y, Tanaka Y, Hayashi M et al (2006) Involvement of CD166 in the activation of human gamma delta T cells by tumor cells sensitized with nonpeptide antigens. J Immunol 177:877–884
Riccieri V, Spadaro A, Parisi G et al (2000) Down-regulation of natural killer cells and of gamma/delta T cells in systemic lupus erythematosus. Does it correlate to autoimmunity and to laboratory indices of disease activity? Lupus 9:333–337
Robak E, Niewiadomska H, Robak T et al (2001) Lymphocyctes Tgammadelta in clinically normal skin and peripheral blood of patients with systemic lupus erythematosus and their correlation with disease activity. Mediators Inflamm 10:179–189
Hirokawa M, Horiuchi T, Kawabata Y et al (2000) Reconstitution of gammadelta T cell repertoire diversity after human allogeneic hematopoietic cell transplantation and the role of peripheral expansion of mature T cell population in the graft. Bone Marrow Transplant 26:177–185
Escribano L, Ocqueteau M, Almeida J et al (1998) Expression of the c-kit (CD117) molecule in normal and malignant hematopoiesis. Leuk Lymphoma 30:459–466
Takeda H, Yamamoto M, Morita N et al (2005) Relationship between Thy-1 expression and cell-cycle distribution in human bone marrow hematopoietic progenitors. Am J Hematol 79:187–193
Acknowledgements
The authors thank Dr. Ian Bruce, ARC Epidemiology Unit, University of Manchester, UK and Dr. Neil Snowden, Department of Rheumatology, North Manchester General Hospital, UK for their review of this manuscript.
The study was supported by grants from the Chinese Education Ministry (20050315001), the Jiangsu Province Natural Science (BK2006007, BK2004009) and the Jiangsu Province 135 Talent Foundation (RC2002003).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sun, Ly., Zhou, Kx., Feng, Xb. et al. Abnormal surface markers expression on bone marrow CD34+ cells and correlation with disease activity in patients with systemic lupus erythematosus. Clin Rheumatol 26, 2073–2079 (2007). https://doi.org/10.1007/s10067-007-0621-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-007-0621-2