Serum neopterin, tumor necrosis factor-alpha and soluble tumor necrosis factor receptor II [p75] levels and disease activity in patients with systemic lupus erythematosus

ABSTRACT

This study was undertaken to determine the clinical value of assaying serum levels of neopterin, tumor necrosis factor-alpha [TNF-alpha] and soluble tumor necrosis factor receptor II [p75] [sTNFRII] and the development of major flares [active disease] in patients with systemic lupus erythematosus [SLE] manifested clinically with lupus nephritis [LN], neuropsychiatric lupus erythematosus [NPLE] or vasculitis. Patients and Serum concentrations of neopterin, TNF-alpha and its soluble receptor sTNFRII p75 were studied in 40 female patients with SLE at various degrees of disease activity and in 10 matched for age and sex healthy controls by enzyme linked immunosorbent assay [ELISA]. SLE disease activity index [SLEDAI] score was used to assess disease activity. Thirty five, 30 and 28 of patients had LN, NPLE and vasculitis respectively as the main clinical manifestation. Renal biopsies were taken from 35 SLE patients who manifested with nephritis. Their pathology revealed that 7, 8, 9 and 10 had mesangial, membranous, focal and lastly diffuse LN. Of the 30 patients with NPLE, six patients were classified as having mild, 9 as having moderate, and 15 as having severe NPLE. Twenty eight of SLE patients manifested with vasculitis in the form of skin gangrene and ulcer or nail infarction or splinter hemorrhage. Serum levels of neopterin, TNF-alpha and sTNFRII of SLE patients were significantly higher than those of healthy controls [p<0.0001 for all]. While, TNF-alpha/ sTNFRII ratio was decreased significantly in SLE patients compared to healthy subjects [p<0.0001]. sTNFRII and TNF-alpha/sTNFRII were the only parameters that showed significantly higher or lower levels in SLE patients with mild activity classified according to SLEDAI score compared to normal subjects [p=0.0004, 0.0001]. Otherwise, the levels of neopterin, TNF-alpha and sTNFRII were significantly higher in either moderate or severe activity as scored by SLEDAI score compared to normal subjects [in moderate for neopterin, TNF-alpha, sTNFRII p=0.0001, 0.03, 0.0001; for severe p= 0.0001 for all respectively]. Patients with focal and diffuse LN had significantly increased serum levels of neopterin, TNF-alpha and sTNFRII, and a significantly higher SLEDAI score in comparison with those patients without LN [in focal for neopterin, TNF-alpha, sTNFRII and score p=0.001, 0.01, 0.0001, 0.0002; for diffuse p=0.0002,0.0004, 0.0001. 0.0001 respectively]. Patients with membranous LN had only increased sTNFRII level in comparison with those patients without LN [p=0.03]. Serum concentration of neopterin. TNF-alpha and sTNFRII were significantly elevated in both moderate, and severe NPLE and also patients' SLEDAI score as compared to those patients without NPLE [in moderate neopterin, TNF-alpha, sTNFRII and score p= 0.008, 0.04, 0.001, 0.001 and in severe NPLE p =0.0001 for all respectively]. Serum concentrations of TNF-alpha and SLEDAI score were significantly higher in patients with severe NPLE than in mild NPLE [p=0.009, 0.004 respectively]. Serum concentration of neopterin was significantly elevated only in the mild NPLE [p=0.02] as compared to those patients without NPLE. Patients with vasculitis had significantly increased score and elevation of serum neopterin, TNF-alpha and sTNFRII compared to patients without vasculitis [p=0.02, 0.02, 0.0001, 0.009 respectively]. SLEDAI score were correlated positively with serum neopterin, TNF-alpha, sTNFRII and TNF-alpha/ sTNFRII levels [r=0.77, 0.75, 0.83, 0.35; p<0.0001 for the first 3 and 0.02 for the last respectively]. Also, serum neopterin levels showed significant positive correlation with serum TNF-alpha, sTNFRII and TNF-alpha/ sTNFRII levels [r=0.89, 0.94, 0.40 p<0.0001 for the first 2 and 0.008 for the last respectively] Measurement of serum sTNFRII is more better than TNF-alpha as a predictor of mild activity of SLE. However, serum neopterin is a useful parameter for detection of mild NPLE. Serum sTNFRII is a good parameter for better detection of all pathological types of lupus nephritis. Also, it was the one amongst other parameters measured that exhibited the higher significant elevation when comparing patients with different LN pathology. Even more, SLEDAI score showed the highest correlation with sTNFRII Lastly, TNF-alpha showed the highest significant elevation in patients with vasculitis