Soluble CD95 concentrations are increased in patients with severe systemic lupus erythematosus, but not in their first degree relatives.
OBJECTIVE
Plasma concentrations of soluble CD95 (sCD95) are raised in patients with systemic lupus erythematosus (SLE) before clinical relapses become manifest. Increased sCD95 concentrations may therefore be a familial characteristic that is associated with susceptibility to severe disease. To test this, sCD95 concentrations were measured in healthy first degree relatives of patients with severe and non-severe SLE.


METHODS
Seventy seven first degree relatives of 26 patients with severe, and 72 relatives of 25 patients with non-severe lupus were studied. Controls were 42 first degree relatives of 17 patients with chronic cutaneous lupus erythematosus (CCLE) and 63 partners of the patients with their first degree relatives. Severe lupus was defined as both multi-organ disease and cyclophosphamide treatment, non-severe lupus as neither. Organ damage was assessed with the SLICC-ACR index, disease activity with SLEDAI.


RESULTS
Soluble CD95 concentrations in relatives of patients with severe SLE were similar to those in relatives of patients with non-severe SLE, relatives of patients with CCLE, and controls (median (interquartile range) sCD95 concentration 0.59 (0.52-0.66) v 0.57 (0.50-0.63), 0.56 (0.51-0.71), and 0.55 (0.49-0.61) ng/ml, p=0.25, p=0.94, and p=0.17, respectively). Increased concentrations of sCD95, however, were found in patients with severe SLE compared with those in patients with non-severe SLE, patients with CCLE, and control relatives (0.77 (0.70-0.97) v 0.60 (0.54-0.67), 0.57 (0.54-0.71), and 0.57 (0.52-0.63) ng/ml, respectively, p<0.001). Concentrations of sCD95 were significantly correlated with damage index scores (rs=0.47, p<0.01). Basic and clinical characteristics of patients with SLE, including SLEDAI scores, could not explain these observations.


CONCLUSIONS
Soluble CD95 concentrations are associated with severity of the disease and not with susceptibility for severe SLE.
van der Linden
M W
MW
Department of Clinical Epidemiology, Leiden University Medical Centre, The Netherlands.
van Lopik
T
T
Aarden
L A
LA
Westendorp
R G
RG
Huizinga
T W
TW
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016014:Linear Models; D008178:Lupus Erythematosus, Cutaneous / Q000097:blood / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D019014:fas Receptor / Q000097:blood*
D015415:Biomarkers; D007166:Immunosuppressive Agents; D019014:fas Receptor; D003520:Cyclophosphamide