Background Current laboratory markers lack sensitivity and specificity in differentiating renal activity and damage in lupus nephritis. Significant kidney damage can occur before renal function is impaired and detected by laboratory parameters1. Interlekin(IL)-18 is a proinflammatory cytokine, which has been involved in and aggravated the progress of many primary and secondary kidney diseases2,3.
Objectives To study the relation between serum IL18 and its renal expression with histological classification of lupus nephritis in patients without significant proteinuria, in order to evaluate serum IL18 as a biomarker of subclinical renal affection in lupus patients.
Methods Forty lupus patients with proteinuria less than 0.5g/24 hours and twenty healthy controls were included. Patients diagnosed according to the 1997 updated American College of Rheumatology revised Criteria for diagnosis of lupus4. Patients underwent full history taking, thorough clinical examination, assessment of disease activity according to modified lupus disease activity index (SLEDAI)5, measurement of serum IL18 and renal biopsies for histopathological assessment and Immunostaining for tissue expression IL18.
Results Lupus patients had a significantly higher serum IL18 level than controls (612.4 and 209.3 pg/ml respectively; p<0.01). Serum IL18 was significantly higher in patients with grades III, IV and V lupus nephritis (609.1, 833.1 and 790 pg/ml respectively) than in patients with grade I and II (370 and 476.8 pg/ml respectively). Immunostaining of IL18 showed glomerular expression in classes IV and V, glomerular and tubular infiltration in class III, tubular pattern in class II and no staining in class I. Patients with diffuse glomerular IL18 staining had higher levels of serum IL18 than those with no staining (840.8 and 522.9pg/ml respectively; p=0.0). Those with diffuse tubular IL18 staining had higher levels of serum IL18 than those with no staining (514.2 and 393 pg/ml respectively; p< 0.05). Serum IL18 correlated with serum creatinine and the activity index of renal biopsies. Serum IL18 did not correlate significantly with lupus disease activity, protein/creatinine in urine nor with any of the laboratory data of patients.
Conclusions Serum IL18 reflects the extent of renal injury in lupus even in absence of significant proteinuria regardless of the level of disease activity; suggesting its role in pathogenesis of lupus nephritis and it could be used as a biomarker that differentiates the histological classes of subclinical lupus nephritis.
Mok CC (2010): Biomarkers for lupus nephritis: a critical appraisal. J Biomed Biotechnol;638413
Calvani N, Richards HB, Tucci M, et al (2004): Up-regulation of IL18 and predominance of a Th1 immune response is a hallmark of lupus nephritis. Clin Exp Immunol;138:171-8
Liang D, Ma W, Yao C, et al (2006): Imbalance of IL18 and IL18 binding protein in patients with lupus nephritis. Cell Mol Immunol; 3:303-6.
Hochberg MC (1997): Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthritis Rheum; 40:1725.
Bombardier C, Gladman DD, Urowitz MB, et al (1992): Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on prognosis Studies in SLE. Arthritis Rheum; 35:630-40.
Disclosure of Interest: None Declared