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Egyptian Rheumatology and Rehabilitation
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Urinary lipoxin A4 as a biomarker for systemic lupus erythematosus

Egyptian Rheumatology and Rehabilitation volume 42, pages 55–61 (2015)Cite this article

Abstract

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disorder that has multiorgan involvement. The continuation of inflammation in lupus could be attributed to failure of the resolution process because of deficiency of potent endogenous proresolution-inducing molecules such as lipoxin A4 (LXA4), leading to progression and flares of lupus and lupus nephritis.

Objective

The aim of this study was to assess the levels of urinary LXA4 in SLE patients and in healthy controls, and to correlate them with various clinical and laboratory data as well as renal biopsy and disease activity indices (DAIs).

Patients and methods

A total of 40 adult female SLE patients were included in this study. Forty healthy women age-matched with SLE patients served as the control group. All patients were subjected to a full assessment of history, clinical examination, assessment of DAIs (SLEDAI and renal SLEDAI), and laboratory investigations including the urinary LXA4/creatinine ratio assessed by enzyme linked immunosorbent assay.

Results

Urinary LXA4/creatinine ratio levels were found to be significantly higher in all SLE patients compared with the healthy controls (P = 0.037). The median level of the urinary LXA4/creatinine ratio was lower in SLE patients with nephritis than in patients without nephritis (0.1 and 0.3 ng/ml, respectively), but with no statistical significance (P = 0.11). The urinary LXA4/creatinine ratio levels were found to be significantly lower in SLE patients with cardiovascular manifestations as well as those with neuropsychiatric manifestations (P = 0.009, 0.04 respectively).

Conclusion

This was a novel study that was carried out to assess the levels of urinary LXA4 in SLE patients. It showed that the urinary LXA4/creatinine ratio levels were significantly lower in SLE patients with cardiovascular and neuropsychiatric manifestations and nonsignificantly lower in patients with nephritis, suggesting that insufficiency of LXA4 in the human body may be responsible for major organ involvement in SLE patients. Accordingly, LXA4 is suggested to be an inflammatory biomarker not only for lupus nephritis but also for other systemic manifestations in SLE.

References

  1. Dall’Era M, Wofsy D. Clinical features of systemic lupus erythematosus. In: eds Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR. Kelley’s Textbook of Rheumatology. 9th ed. Philadelphia, PA: Saunders, an imprint of Elsevier Inc.; 2013: 1283–1303.

    Chapter  Google Scholar 

  2. Yap DYH, Lai KN. The role of cytokines in the pathogenesis of systemic lupus erythematosus – from bench to bedside. Nephrology 2013; 18: 243–255.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  4. El-Shehaby A, Darweesh H, El-Khatib M, Momtaz M, Marzouk S, El-Shaarawy N, Emad Y. 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 

  5. Serhan CN, Krishnamoorthy S, Recchiuti A, Chiang N. Novel anti-inflammatory – pro-resolving mediators and their receptors. Curr Top Med Chem 2011; 11:629–647.

    Article  CAS  Google Scholar 

  6. Schwab JM, Chiang N, Arita M, Serhan CN. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 2007; 447:869–874.

    Article  CAS  Google Scholar 

  7. Recchiuti A, Serhan CN. Proresolving lipid mediators (SPMs) and their actions in regulating miRNA in novel resolution circuits in inflammation. Front Immunol 2012; 3:298.

    Article  Google Scholar 

  8. Serhan CN, Chiang N, van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 2008; 8:349–361.

    Article  CAS  Google Scholar 

  9. Das UN. Lipoxins as biomarkers of lupus and other inflammatory conditions. Lipids Health Dis 2011; 10:76.

    Article  CAS  Google Scholar 

  10. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40:1725.

    Article  CAS  Google Scholar 

  11. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992; 35:630–640.

    Article  CAS  Google Scholar 

  12. Pitashny M, Schwartz N, Qing X, Hojaili B, Aranow C, Mackay M, Putterman C Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritis. Arthritis Rheum 2007; 56:1894–1903.

    Article  CAS  Google Scholar 

  13. Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. International Society of Nephrology Working Group on the Classification of Lupus Nephritis; Renal Pathology Society Working Group on the Classification of Lupus Nephritis The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 2004; 65:521–530.

    Article  Google Scholar 

  14. Li Y, Fang X, Li QZ. Biomarker profiling for lupus nephritis. Genomics Proteomics Bioinformatics 2013; 11:158–165.

    Article  CAS  Google Scholar 

  15. Wu SH, Liao PY, Yin PL, Zhang YM, Dong L. Inverse temporal changes of lipoxin A4 and leukotrienes in children with Henoch–Schönlein purpura. Prostaglandins Leukot Essent Fatty Acids 2009; 80:177–183.

    Article  CAS  Google Scholar 

  16. Merched AJ, Ko K, Gotlinger KH, Serhan CN, Chan L Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB J 2008; 22:3595–606.

    Article  CAS  Google Scholar 

  17. Nascimento-Silva V, Arruda MA, Barja-Fidalgo C, Fierro IM. Aspirin-triggered lipoxin A4 blocks reactive oxygen species generation in endothelial cells: a novel antioxidative mechanism. Thromb Haemost 2007; 97:88–98.

    Article  CAS  Google Scholar 

  18. Das UN. Lipoxin A4 may function as an endogenous anti-arrhythmic molecule. Med Hypotheses; 2011; 76:14–16.

    Article  CAS  Google Scholar 

  19. Ye XH, Wu Y, Guo PP, Wang J, Yuan SY, Shang Y, Yao SL Lipoxin A4 analogue protects brain and reduces inflammation in a rat model of focal cerebral ischemia reperfusion. Brain Res 2010; 1323: 74–83.

    Article  Google Scholar 

  20. Yao C, Yang D, Wan Z, Wang Z, Liu R, Wu Y, et al. Aspirin-triggered lipoxin A4 attenuates lipopolysaccharide induced inflammatory response in primary astrocytes. Int Immunopharmacol 2014; 18:85–89.

    Article  CAS  Google Scholar 

  21. Wu SH, Liao PY, Yin PL, Zhang YM, Dong L. Elevated expressions of 15-lipoxygenase and lipoxin A4 in children with acute poststreptococcal glomerulonephritis. Am J Pathol 2009; 174:115–122.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Rheumatology and Rehabilitation, Faculty of Medicine, Cairo University, Giza, Egypt

    Manal M. Sedky Abdou, Dina A. Effat & Noha M. Abd El Baky MSc

  2. Clinical & Chemical Pathology, Faculty of Medicine, Cairo University, Giza, Egypt

    Lamiaa A. Mansour & Mona M. Abdul Salam

Authors
  1. Manal M. Sedky Abdou
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  2. Dina A. Effat
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  3. Lamiaa A. Mansour
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  4. Noha M. Abd El Baky MSc
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  5. Mona M. Abdul Salam
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Correspondence to Noha M. Abd El Baky MSc.

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Sedky Abdou, M.M., Effat, D.A., Mansour, L.A. et al. Urinary lipoxin A4 as a biomarker for systemic lupus erythematosus. Egypt Rheumatol Rehabil 42, 55–61 (2015). https://doi.org/10.4103/1110-161X.157861

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  • DOI: https://doi.org/10.4103/1110-161X.157861

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