Serum interleukin-1 receptor antagonist: clinicopathological correlations with lupus nephritis

ABSTRACT

To evaluate the relationship between serum interleukin-1 receptor antagonist [IL-1ra] concentrations and renal involvement in SLE and to study its impact on laboratory, immunological and renal histopathological findings in SLE patients as well as its association with disease activity. We studied 26 [23 females, 3 males] SLE patients who had distinct clinical manifestations [22 had vasculitic skin rash, 20 had photosensitivity, 13 had oral ulcerations, 8 had neuropsychiatric manifestations]. They were classified into two subgroups; group Ia included 18 patients who had impaired renal function, 14 of them were proved by renal biopsy and group Ib that included 8 patients without renal affection. Ten healthy subjects matched for age and sex with the patient group were taken as a control group [group II] All patients were subjected to full history taking with stress on clinical manifestations of renal dysfunction, serum samples were tested for interleukin-1 receptor antagonist [IL-1ra] in addition to levels of C3, C4, creatinine levels and for the presence of anti ds-DNA antibodies. Light and electron microscopic examination [LM and EM respectively] of renal biopsy samples were performed for patients of group Ia. The 14 biopsy samples were classified according to the world health organization [WHO] classification as follows Class I and II [inactive nephritis] n=1, class III and IV [active nephritis], n=11 and class V, n=2. The activity index [AI] and chronicity index [CI] in those 14 renal biopsy specimens were also determined. This study showed that the pattern of IL-1ra in active SLE varies in a manner that is dependent on which organs are involved. Serum IL-1ra concentrations were compared to normal blood donors [t=3.28, p<0.0001 highly significant]. However, significant higher levels of IL-1ra were observed in patients with extra-renal disease group Ib as compared to other patients group Ia [mean +/- SD were 1006.3 +/- 823.9 pg/ml, range 470-3000 and 147.1 +/- 58.5 and range 53-260 pg/ml] for patients without and with renal involvement respectively]. Elevated IL-1ra concentrations in patients with renal manifestations correlated positively with C3 and C4 levels [r=0.56 and 0.36 respectively] and negatively with degree of proteinuria and serum creatinine levels [-0.44 and -0.4 respectively] but not with disease activity index score SLEDAI [r=0.16]. Moreover, there was a high significant difference between the group of patients who were negative for anti ds-DNA [n=4] and those who where positive [n=22] as regards serum IL-1ra levels, being significantly lower in the positive group who were positive for anti ds DNA [t=2.8, p <0.01]. Furthermore, the highermost level of IL-1ra in group Ia [with renal impairment] was 260 pg/ml and the lowermost level of IL-1ra in group Ib was 470 pg/ml so a cut off value was selected at 370 pg/ml and the sensitivity and specificity values for IL-1ra for detection and diagnosis of lupus nephritis were found to be 100% for both. Therefore, a relative decrease of IL-1ra response appears to be a feature characteristic of kidney involvement and IL-1ra elevation clearly correlates with SLE involving other organs. So it may be a useful marker of lupus nephritis