The apoptosis-1/Fas protein in human systemic lupus erythematosus.

Abstract

Three independent mutations involving the apoptosis-1 (APO-1)/Fas receptor or its putative ligand have led to lupuslike diseases associated with lymphadenopathy in different strains of mice. To determine whether humans with SLE also have a defect in this apoptosis pathway, we analyzed the expression of APO-1 on freshly isolated blood mononuclear cells and on lymphocytes activated in vitro using flow cytometry and the monoclonal antibody anti-APO-1. Significantly higher levels of APO-1 expression were detected on freshly isolated peripheral B cells and both CD4' and CD8' T lymphocyte populations obtained from lupus patients when compared with normal controls (P < 0.001). Almost 90% of the cells that stained positive for APO-1 also expressed the CD29 antigen, suggesting that APO-1 was upregulated after lymphocyte activation in vivo. No defect in APO-1 regulation was detected after activation of SLE T (with anti-CD3) or B (with Staphylococcus aureus Cowan 1) lymphocytes in the presence of IL-2 in vitro. Similarly, the anti-APO-1 antibody induced apoptosis in 74±5% of activated SLE T cells in vitro compared with 79±6% of the normal controls (P > 0.05). These results reveal that, while APO-1 / Fas may play an important role in the regulation of lymphocyte survival in SLE, no consistent defect in the expression or function of the receptor could be detected in these studies. (J. Clin.

In vitro apoptosis and expression of apoptosis‐related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases

“…We focused on these proteins because 2 of the SLE mouse models mentioned above are based on genetic alterations in these genes. Similar to the findings in previously reported studies (34,58) we found more T lymphocytes expressing Fas/APO-1 in freshly isolated SLE cells compared with normal donor cells. Notably, convincing data showing that signaling through Fas/APO-1 can induce apoptosis in SLE cells have recently been published (34,58).…”

“…Fas/APO-1, an apoptosis-inducing protein, was found to be expressed in higher quantities on SLE lymphocytes (34). However, 2 different groups of investigators found the apoptosis-inhibiting protein bcl-2 expressed in higher intensity as well (35,36), whereas another group did not detect any differences in bcl-2 expression between SLE and normal donor cells (37).…”

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

“…CD95, which has been implicated in AICD of preactivated mature T cells, was predominantly expressed on CD45RO 'memory' T cells, but not on CD45RA 'naive' T cells in NC. Consistent with previous reports [36,37], a significant up-regulation of CD95 was observed in CD45RA T cells from SLE. There was no apparent difference in expression patterns of CD95 between CD4 and CD8 T cell subsets (not shown).…”

“…It remains to be determined whether these CD95 high cells in the CD28 population are indeed susceptible to AICD. However, despite up-regulation of CD95 expression, increased apoptosis in SLE PBMC and B cells by the agonistic anti-CD95 MoAb in freshly isolated PBMC was not observed [37]. In addition, several reports indicate that expression of CD95 is not always associated with CD95-mediated apoptosis [52][53][54].…”

Antibodies against p53 in sera from patients with systemic lupus erythematosus and other rheumatic diseases

“…Babies with NLE have maternal autoantibodies against Ro/SS-A and/or La/SS-B (1,2). Although previous immunogenetic studies have suggested that the frequencies of HLA-DR3 and DQ2 were increased among mothers of NLE infants in white and North American black populations (1,3), and a few investigators have questioned whether fetal HLA antigens are contributory, no prior study has addressed whether the maternal-fetal HLA relationship affects the immunopathogenesis of NLE. We report herein the results of a haplotypic analysis of HLA-DR, DQ, and DP alleles in Japanese NLE child/mother pairs.…”