Top

Published in:

01-10-2011

Correlations of Urinary Biomarkers, TNF-Like Weak Inducer of Apoptosis (TWEAK), Osteoprotegerin (OPG), Monocyte Chemoattractant Protein-1 (MCP-1), and IL-8 with Lupus Nephritis

Authors: Amal El-shehaby, Hanan Darweesh, Mohamed El-Khatib, Mohamed Momtaz, Samar Marzouk, Nashwa El-Shaarawy, Yasser Emad

Published in: Journal of Clinical Immunology | Issue 5/2011

Abstract

Objective

This case-controlled study was designed to correlate urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) levels, with renal involvement in a cohort of systemic lupus erythematosus (SLE) patients to examine their diagnostic performance.

Patients and Methods

In 73 SLE patients, and in 23 healthy volunteers, urinary levels of TWEAK, OPG, MCP-1, and IL-8 levels were measured. Disease activity was assessed by total SLE disease activity index, and renal activity by renal activity index (rSLEDAI), and both were correlated with urinary biomarkers. Sensitivity, specificity, and predictive values of individual biomarkers to predict lupus nephritis were also calculated.

Results

Significantly higher levels of urinary biomarkers were observed in SLE patients with lupus nephritis (LN) compared with those without LN (TWEAK, p < 0.001; MCP-1, p < 0.001; OPG, p < 0.001; IL-8, p < 0.032). Other significantly higher levels were observed in SLE patients with LN compared with control subjects (TWEAK, MCP-1, OPG, and IL-8 p < 0.001). Positive correlations were observed between rSLEDAI and TWEAK (r = 0.612 and p < 0.001), MCP-1 (r = 0.635 and p < 0.001), and OPG (r = 0.505 and p < 0.001).

Conclusions

Urinary levels of TWEAK, OPG, and MCP-1 positively correlate with renal involvement as assessed by rSLEDAI with reasonable sensitivity, specificity, and predictive values to detect lupus nephritis while IL-8 was not significantly associated with global or rSLEDAI.

Seshan SV, Jennette JC. Renal disease in systemic lupus erythematosus with emphasis on classification of lupus glomerulonephritis: advances and implications. Arch Pathol Lab Med. 2009;133:233–48.PubMed

Korbet SM, Lewis EJ, Schwartz MM. Factors predictive of outcome in severe lupus nephritis. Lupus Nephritis Collaborative Study Group. Am J Kidney Dis. 2000;35:904–14.PubMedCrossRef

Illei GG, Tackey E, Lapteva L, Lipsky PE. Biomarkers in systemic lupus erythematosus: II. Markers of disease activity. Arthritis Rheum. 2004;50(7):2048–65.PubMedCrossRef

Chicheportiche Y, Bourdon PR, Xu H, Hsu YM, Scott H, Hession C, et al. TWEAK a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J Biol Chem. 1997;272:32401–10.PubMedCrossRef

Wiley SR, Cassiano L, Lofton T, Davis-Smith T, Winkles JA, Lindner V, et al. A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis. Immunity. 2001;15:837–46.PubMedCrossRef

Campbell S, Michaelson J, Burkly LC, Putterman C. The role of TWEAK/Fn14 in the pathogenesis of inflammation and systemic autoimmunity. Front Biosci. 2004;8:2273–84.CrossRef

Zhao Z, Burkly LC, Campbell S, Schwartz N, Molano A, Choudhury A, et al. TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the chronic graft-versus-host model of systemic lupus erythematosus. J Immunol. 2007;179:7949–58.PubMed

Schwartz N, Rubinstein T, Burkly LC, Collins CE, Blanco I, Su L, et al. Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study. Arthritis Res Ther. 2009;11(5):R143.PubMedCrossRef

Gao HX, Campbell S, Burkly LC, Jarchun I, Banas B, Schlondorff D, et al. TNF-like weak inducer of apoptosis (TWEAK) stimulates human kidney cells to elaborate chemokines central to the pathogenesis of lupus nephritis [Abstract]. Arthritis Rheum. 2006;54(Suppl):S602.

10.

Schwartz N, Su L, Burkly LC, Mackay M, Aranow C, Kollaros M, et al. Urinary TWEAK and the activity of lupus nephritis. J Autoimmun. 2006;27(4):242–50.PubMedCrossRef

11.

Rovin BH, Birmingham DJ, Nagaraja HN, Yu CY, Hebert LA. Biomarker discovery in human SLE nephritis. Bull NYU Hosp Jt Dis. 2007;65(3):187–93.PubMed

12.

Wada T, Yokoyama H, Su SB, Mukaida N, Iwano M, Dohi K, et al. Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis. Kidney Int. 1996;49(3):761–7.PubMedCrossRef

13.

Noris M, Bernasconi S, Casiraghi F, Sozzani S, Gotti E, Remuzzi G, et al. Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine of patients with lupus nephritis. Lab Invest. 1995;73(6):804–9.PubMed

14.

Segerer S, Nelson PJ, Schlondorff D. Chemokines, chemokine receptors, and renal disease: from basic science to pathophysiologic and therapeutic studies. J Am Soc Nephrol. 2000;11:152–76.PubMed

15.

Kelley VR, Rovin BH. Chemokines: therapeutic targets for autoimmune and inflammatory renal disease. Springer Semin Immunopathol. 2003;24:411–21.PubMedCrossRef

16.

Rovin BH, Phan LT. Chemotactic factors and renal inflammation. Am J Kidney Dis. 1998;31:1065–84.PubMedCrossRef

17.

Kiani AN, Johnson K, Chen C, Diehl E, Hu H, Vasudevan G, et al. Urine osteoprotegerin and monocyte chemoattractant protein-1 in lupus nephritis. J Rheumatol. 2009;36(10):2224–30.PubMedCrossRef

18.

Tesar V, Masek Z, Rychlík I, Merta M, Bartůnková J, Stejskalová A, et al. Cytokines and adhesion molecules in renal vasculitis and lupus nephritis. Nephrol Dial Transplant. 1998;13:1662–7.PubMedCrossRef

19.

Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25(11):1271–7.PubMedCrossRef

20.

Bombardier C, Gladman D, Urowitz M. Committee on prognosis studies in systemic lupus erythematosus. The derivation of the SLEDAI: a disease activity index for lupus patients. Arthritis Rheum. 1992;35:630–40.PubMedCrossRef

21.

Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29:288–91.PubMed

22.

Churg J, Sobin LH. Renal disease: classification and atlas of glomerular disease. Tokyo: Igaku-Shoin; 1982.

23.

Campbell S, Burkly LC, Gao H, Berman JW, So L, Browning B, et al. Proinflammatory effects of TWEAK/Fn14 interactions in glomerular mesangial cells. J Immunol. 2006;176:1889–98.PubMed

24.

Mok CC. Biomarkers for lupus nephritis: a critical appraisal. J Biomed Biotechnol. 2010;2010:638413.PubMedCrossRef

25.

El-Gendi SS, El-Sherif WT. Anti-C1q antibodies, sCD40L, TWEAK and CD4/CD8 ratio in systemic lupus erythematosus and their relations to disease activity and renal involvement. Egypt J Immunol. 2009;16(1):135–48.

26.

Molano A, Lakhani P, Aran A, Burkly LC, Michaelson JS, Putterman C. TWEAK stimulation of kidney resident cells in the pathogenesis of graft versus host induced lupus nephritis. Immunol Lett. 2009;125(2):119–28.PubMedCrossRef

27.

Rovin BH, Song H, Birmingham DJ, Hebert LA, Yu CY, Nagaraja HN. Urine chemokines as biomarkers of human systemic lupus erythematosus activity. J Am Soc Nephrol. 2005;16(2):467–73.PubMedCrossRef

28.

Tucci M, Barnes EV, Sobel ES, Croker BP, Segal MS, Reeves WH, et al. Strong association of a functional polymorphism in the monocyte chemoattractant protein 1 promoter gene with lupus nephritis. Arthritis Rheum. 2004;50(6):1842–9.PubMedCrossRef

29.

Alzawawy A, Zohary M, Ablordiny M, Eldalie M. Estimation of monocyte-chemoattractantprotein-1 (Mcp-1) level in patients with lupus nephritis. Int J Rheum Dis. 2009;12(4):311–8.PubMedCrossRef

30.

Tucci M, Calvani N, Richards HB, Qatar C, Silvestris F. The interplay of chemokines and dendritic cells in the pathogenesis of lupus nephritis. Ann N Y Acad Sci. 2005;1051:421–32.PubMedCrossRef

31.

Tian S, Li J, Wang L, Liu T, Liu H, Cheng G, et al. Urinary levels of RANTES and M-CSF are predictors of lupus nephritis flare. Inflamm Res. 2007;56(7):304–10.PubMedCrossRef

32.

Chan RW, Lai FM, Li EK, Tam LS, Chow KM, Li PK, et al. The effect of immunosuppressive therapy on the messenger RNA expression of target genes in the urinary sediment of patients with active lupus nephritis. Nephrol Dial Transplant. 2006;21(6):1534–40.PubMedCrossRef

33.

Rovin BH, Lu L, Zhang XA. Novel interleukin-8 polymorphism is associated with severe systemic lupus erythematosus nephritis. Kidney Int. 2002;62(1):261–5.PubMedCrossRef

34.

Wada T, Yokoyama H, Tomosugi N, Hisada Y, Ohta S, Naito T, et al. Detection of urinary interleukin-8 in glomerular diseases. Kidney Int. 1994;46(2):455–60.PubMedCrossRef

35.

Tsai CY, Wu TH, Yu CL, Lu JY, Tsai YY. Increased excretions of beta2-microglobulin, IL-6, and IL-8 and decreased excretion of Tamm-Horsfall glycoprotein in urine of patients with active lupus nephritis. Nephron. 2000;85(3):207–14.PubMedCrossRef

Title: Correlations of Urinary Biomarkers, TNF-Like Weak Inducer of Apoptosis (TWEAK), Osteoprotegerin (OPG), Monocyte Chemoattractant Protein-1 (MCP-1), and IL-8 with Lupus Nephritis
Authors: Amal El-shehaby
Hanan Darweesh
Mohamed El-Khatib
Mohamed Momtaz
Samar Marzouk
Nashwa El-Shaarawy
Yasser Emad
Publication date: 01-10-2011
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 5/2011
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-011-9555-1

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Patients and Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 5/2011

Severe Combined Immunodeficiency in Greek Children over a 20-Year Period

Decreased Expression in Nuclear Factor-κB Essential Modulator Due to a Novel Splice-Site Mutation Causes X-linked Ectodermal Dysplasia with Immunodeficiency

Incidence of Infection is Inversely Related to Steady-State (Trough) Serum IgG Level in Studies of Subcutaneous IgG in PIDD

Defective T Cell Chemotaxis to Sphingosine 1-Phosphate and Chemokine CCL21 in Idiopathic T Lymphocytopenia

Efficacy and Safety of Hizentra®, a New 20% Immunoglobulin Preparation for Subcutaneous Administration, in Pediatric Patients with Primary Immunodeficiency

KRN/I-Ag7 Mouse Arthritis Is Independent of Complement C3

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials