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Egyptian Rheumatology and Rehabilitation
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Role of tumor necrosis factor-like weak inducer of apoptosis/ fibroblast growth factor-inducible molecule 14 pathway in lupus nephritis

Egyptian Rheumatology and Rehabilitation volume 45, pages 182–187 (2018)Cite this article

Abstract

Objectives

To evaluate urinary tumor necrosis factor-like weak inducer of apoptosis (uTWEAK) levels as well as renal fibroblast growth factor-inducible molecule 14 (Fn14) expression by immunohistochemistry in patients with systemic lupus erythematosus (SLE) to assess the possible role of TWEAK level as an indicator of lupus nephritis (LN) and its relation to disease activity as well as pathological LN classification.

Patients and methods

Urinary levels of TWEAK using enzyme-linked immunosorbent assay and chemical and immunological markers of SLE were measured in 30 patients with SLE and 15 age-matched and sex-matched apparently healthy controls. Patients with SLE were divided into two subgroups: 15 patients with LN and 15 without LN. Disease activity was assessed using systemic lupus erythematosus disease activity index SLE disease activity index (SLEDAI). Fn14 was examined in renal biopsies from LN group by immunohistochemistry.

Results

A significantly higher uTWEAK level was found in patients having SLE with LN compared with those without LN and controls (F=149.2, P<0.001). uTWEAK had a highly significant positive correlation with proteinuria (r=0.755, P<0.001) and a significant positive correlation with tSLEDAI and rSLEDAI (r=0.217, P<0.037 and r=0.476, P<0.024, respectively). uTWEAK had a significant negative correlation with anti-dsDNA titer, C3, and C4 (r=−0.579, P<0.008; r=−0.456, P<0.011; and r=−0.552, P<0.002, respectively). Fn14 expression was detected in mesangial and tubular cells, mainly proximal tubular cells, in patients with LN.

Conclusion

uTWEAK is a specific and sensitive biomarker for detection of active LN.

References

  1. Mohan C, Putterman C. Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis. Nat Rev Nephrol 2015; 11:329–341.

    Article  CAS  Google Scholar 

  2. Kwok SK, Tsokos GC. New insights into the role of renal resident cells in the pathogenesis of lupus nephritis. Korean J Intern Med 2018; 33:284–289.

    Article  CAS  Google Scholar 

  3. Poveda J, Tabara LC, Fernandez-Fernandez B, Martin-Cleary C, Sanz AB, Selgas R, et al. TWEAK/Fn14 and non-canonical NF-kappaB signaling in kidney disease. Front Immunol 2013; 4:447–453.

    Article  Google Scholar 

  4. Michaelson JS, Wisniacki N, Burkly LC, Putterman C. Role of TWEAK in lupus nephritis: a bench-to-bedside review. J Autoimmun 2012; 39:130–142.

    Article  CAS  Google Scholar 

  5. Xu WD, Zhao Y, Liu Y. Role of the TWEAK/Fn14 pathway in autoimmune diseases. Immunol Res 2016; 64:44–50.

    Article  CAS  Google Scholar 

  6. Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64 (8):2677–2686.

  7. Hahn BH, McMahon M, Wilkinson A, Wallace WD, Daikh DI, Fitz Gerald J, et al. American College of Rheumatology Guidelines for screening, case definition, treatment and management of lupus nephritis. Arthritis Care Res 2012; 64:797–808.

    Article  Google Scholar 

  8. Bombardier C, Gladman D, Urowitz M, Caron D. Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum 2012; 35:630–640.

    Google Scholar 

  9. Reyes-Martinez F, Perez-Navarro M, Rodriquez-Matias A, Soto-Abraham V, Gutierrez-Reyes G, Medina-Avila Z, et al. Assessment of urinary TWEAK levels in Mexican patients with untreated lupus nephritis: an exploratory study. Nefrologia 2018; 38:152–160.

    Article  Google Scholar 

  10. Sanz AB, Sanchez-Nino MD, Izquierdo MC, Moreno JA, Ucero AC, Benito-Martin A, et al. TWEAK, the facilitator of acute kidney injury. Nefrologia 2008; 28:587–592.

    CAS  PubMed  Google Scholar 

  11. 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:R143.

  12. Xuejing Z, Jiazhen T, Jun L, Xiangqing X, Shuguang Y, Fuyou L. Urinary TWEAK Level as a Marker of Lupus Nephritis Activity in 46 Cases. J Biomed Biotechnol 2012; 2012:359647.

    Article  Google Scholar 

  13. El-Shehaby A, Darweesh H, El-Khatib M, Momtaz M, Marzouk S, El-Shaarawy N, et al. 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. J Clin Immunol 2011; 31:848–856.

    Article  CAS  Google Scholar 

  14. Izquierdo MC, Sanz AB, Mezzano S, Blanco J, Carrasco S, Sanchez-Nino MD, et al. TWEAK (tumor necrosis factor-like weak inducer of apoptosis) activates CXCL16 expression during renal tubulointerstitial inflammation. Kidney Int 2012; 81:1098–1107.

    Article  CAS  Google Scholar 

  15. Dhaun N, Kluth DC. TWEAK: a novel biomarker for lupus nephritis. Arthritis Res Ther 2009; 11:133–135.

    Article  Google Scholar 

  16. Gonzalez-Sanchez DA, Alvarez CM, Vasquez G, Gomez-Puerta JA. Role of TWEAK/Fn14 signalling pathway in lupus nephritis and other clinical settings. Nefrologia 2017; 37:118–125.

    Article  Google Scholar 

  17. Sharif MN, Campanholle G, Nagiec EE, Wang J, Syed J, O’Neil SP, et al. Soluble Fn14 is detected and elevated in mouse and human kidney disease. PLoS One 2016; 11:e0155368.

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Authors and Affiliations

  1. Physical Medicine, Rheumatology and Rehabilitation Department, Ain Shams University, Cairo, Egypt

    Miriam R. Bekhit MSc, Nadia S. Kamel, Manal O. Mohammed & Nouran M. Abaza

  2. Department of Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Somia A. Saad El Din

Authors
  1. Miriam R. Bekhit MSc
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  2. Nadia S. Kamel
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  3. Manal O. Mohammed
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  4. Nouran M. Abaza
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  5. Somia A. Saad El Din
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Corresponding author

Correspondence to Miriam R. Bekhit MSc.

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Bekhit, M.R., Kamel, N.S., Mohammed, M.O. et al. Role of tumor necrosis factor-like weak inducer of apoptosis/ fibroblast growth factor-inducible molecule 14 pathway in lupus nephritis. Egypt Rheumatol Rehabil 45, 182–187 (2018). https://doi.org/10.4103/err.err_14_18

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  • DOI: https://doi.org/10.4103/err.err_14_18

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