An insight on pathogenesis of systemic lupus erythmatosus-induced anemia of chronic diseases

ABSTRACT

The present study was designed to evaluate the frequency of anemia of chronic diseases [ACD] in patients with systemic lupus erythematosus [SLE] and to estimate serum levels of interleukin-6 [IL-6] and erythropotien [EPO] and to determine the serum positivity for antibodies to human EPO [anti-EPO antibodies] in patients with ACD so as to evaluate their probable role in pathogenesis of ACD. The study included 200 patients with SLE; all underwent clinical evaluation of disease activity using the British Isles Lupus Assessment Group [BILAG] score and laboratory assessment of immunologic parameters. Hemoglobin concentration [Hb cone.] was determined and anemia was defined by haemoglobin concentration [Hb cone.] of women and of men. Blood samples were obtained for ELISA estimation of serum IL-6 and EPO levels and for El.ISA testing for anti-EPO antibodies. Hemogram detected 73 ACD patients [36.5%] with mean Hb cone, of 10.5 +/- 0.8 gm/dl [Anemic group]; the other 127 patients [63.5%] were either not anemic or had other types of anemia [Non-anemic group] with mean Hb cone, of 12.9 +/- 0.5 gm/dl. There was a negative significant correlation between Hb Cone, and hematological activity score. Mean serum IL-6 estimated in patients with SLE was 53.9 +/- 19.9 ng/ml and was significantly [p < 0.05] higher compared to control levels. Moreover, mean serum IL-6 estimated in anemic group [60.9 +/- 23.1 ng/ml] was significantly [p < 0.05] higher compared both to control and non-anemic groups [49.8 +/- 16.5 ng/ml], with a significantly higher [p < 0.05] levels of serum IL-6 in non-anemic SLE patients compared to controls. Mean serum EPO estimated in patients with SLE was 21.2 +/- 12.1 mlU/ml and anti-EPO antibodies [Anti-EPO Positive] were detected in 105 patients [52.5%] while the other 95 patients [47.5%] were negative for anti-EPO antibodies [Anti-EPO Negative]. Mean serum EPO level was significantly [p < 0.05] lower in Anti-EPO Negative patients [14.4 +/- 2 mlU/ml] compared to Anti-EPO Positive patients [28.7 +/- 14 mIU/ml]. Mean serum EPO level was significantly [p < 0.05] higher in anemic [28.9 +/- 16.8 mlU/ml] compared to non-anemic patients [16.7 +/- 3.8 mIU/ml]. There was a negative significant correlation [r = -0.332, p < 0.001] between presence of Anti-EPO antibodies and Hb cone.; however, there was a non-significant difference between Hb cone, between anemic patients with and without anti-EPO antibodies or between non-anemic patients with and without anti-EPO antibodies. There was a negative significant correlation between Hb cone, and serum EPO, [r = -0.256, p = 0.028] and IL-6, [r = -0.246, p = 0.036] and a positive, significant correlation between serum IL-6 and EPO, [r = 0.238, p = 0.043]. Evaluation of specificity of estimated parameters for pathogenesis of SLE-induced anemia using the receiver operating characteristic [ROC] curve analysis judged by the area under the curve [AUC] defined IL-6 as the most specific factor [AU/C = 0.827], followed by positivity for anti-EPO [AUC = 0.662] and the least specific was EPO [AUC = 0.588]. It could be concluded that the frequency of SLE-induced anemia of chronic disease was 36.5% and the presence of anti-EPO antibodies and elevated IL-6 play a complementary role in its pathogenesis