The bcl-2 proto-oncogene is overexpressed in systemic lupus erythematosus.
Systemic Lupus Erythematosus (SLE) is a disease in which lymphoid hyper-reactivity occurs. Whether this is primary or secondary is not always clear. SLE occurs on a well defined genetic background including genes associated with the major histocompatibility complex (MHC) although family studies demonstrate that other genes must be involved as well. Other potential genes include those involved in intrinsic lymphoid hyper-reactivity, for example by preventing programmed cell death. Such examples exist in murine models of SLE, and in this study we provide evidence that one such controlling protein, bcl-2, is expressed in an increased proportion of both B and T cells in SLE patients. The increased expression was not readily related to disease activity measured by the SIS, nor by routine serological markers. This raises the possibility that the increased expression of bcl-2 seen in lymphoid cells from SLE patients may be of intrinsic genetic origin rather than being secondary to the auto-reactive process. Such increased expression could be expected to interfere with programmed cell death, to produce lymphoid hyper-reactivity and to contribute to the induction and maintenance of this prototypic systemic autoimmune disease.
Department of Clinical Immunology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
P A
PA
Gatenby
M
M
Irvine
D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D019938:Cyclin D1; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes
D015415:Biomarkers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019938:Cyclin D1