Induction of apoptosis in monocytes and lymphocytes by serum from patients with systemic lupus erythematosus - an additional mechanism to increased autoantigen load?
The most likely source of autoantigens in systemic lupus erythematosus (SLE) is apoptotic material. Because increased levels of circulating apoptotic cells are found in SLE we wanted to investigate the capacity of serum from patients with SLE or other autoimmune or infectious diseases and normal healthy donors (NHD) to induce apoptosis in normal monocytes, lymphocytes and corresponding cell lines, in relation to clinical and immunological data. Monocytes and lymphocytes from healthy donors were incubated with sera from 37 SLE patients, 37 sex- and age-matched NHD and sera from patients with rheumatoid arthritis, vasculitis, sepsis and mononucleosis. Sera from SLE patients were sampled at both active and inactive disease. The apoptosis-inducing effect (AIE) of these sera was monitored with flow cytometry using annexin V and propidium iodide (PI) binding. The AIE in monocytes and lymphocytes was significantly higher in sera from SLE patients than in other patient groups and NHD (P < 0.001) and was also higher when cell lines were used. Level of C5a in cell culture supernatant correlated with AIE in monocytes (r = 0.451, P = 0.005), suggesting involvement of complement. Heat-inactivation of sera did not affect the AIE, nor did depletion of IgG by protein G absorption of serum. Kinetic analyses showed a peak in apoptosis induction at 12-16 h, with a delayed PI positivity. AIE was equally high using sera from active and inactive SLE cases, and did not correlate with the SLE Disease Activity Index (SLEDAI). Thus, SLE serum has a strong and apparently disease-specific apoptosis-inducing capacity, which could contribute to a high load of potential autoantigen.
Department of Rheumatology, Lund University, Lund, Sweden.
A A
AA
Bengtsson
G
G
Sturfelt
B
B
Gullstrand
L
L
Truedsson
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D001324:Autoantigens / Q000097:blood*; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D003165:Complement System Proteins / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology; D008214:Lymphocytes / Q000473:pathology*; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology*
D001324:Autoantigens; D003165:Complement System Proteins