Skip to main content

Study the relationship between vitamin A deficiency, T helper 17, regulatory T cells, and disease activity in patients with systemic lupus erythematosus

Abstract

Background

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with activation of the innate and adaptive immune systems. Vitamin A deficiency causes imbalance of T helper 17 (Th17) and regulatory T cell (Treg), deteriorating the progression of SLE.

Aim

To determine the relationship between vitamin A levels and Th17 and Treg level in patients with SLE and its relation to disease activity.

Patients and methods

A total of 45 female patients with SLE diagnosed according to the American College of Rheumatology criteria and 45 healthy age-matched and sex-matched patients as control group were included. Full assessment was done including medications, clinical examination (pain evaluation by visual analogue scale and assessment of disease activity by SLE disease activity index), laboratory investigations, and albumin–creatinine ratio. Serum levels of vitamin A were measured by a human KAMIYA kits, and flow cytometry was used for measuring Th17 and Treg percentages.

Results

There was a significant deficiency of vitamin A level in patients with SLE compared with controls (P=0.001). There was a significant negative correlation between vitamin A and Th17 (P=0.001) and positive correlation between vitamin A and Treg percentages (P=0.001). There was a negative correlation between vitamin A levels and albumin–creatinine ratio in patients with SLE (R=-0.255). A positive correlation between serum levels of vitamin A and C3 and C4 was found (P=0.001).

Conclusion

Vitamin A deficiency is a bad prognostic factor in patients with SLE, affecting Th17/ Treg balance. Routine use of retinoic acid may be a promising supplementary agent in patients with SLE, improving its prognosis.

References

  1. Joo YB, Park CSY, Won S, Bae S, Danilenko DM, Valdez P. Differences in clinical features and mortality between childhood-onset and adult-onset systemic lupus erythematosus: a prospective single-center study. J Rheumatol 2016; 43:1490–1497.

    Article  Google Scholar 

  2. Szmyrka-Kaczmarek M, Kosmaczewska A, Ciszak L, Szeteblich A, Wiland P, Hakim R. Peripheral blood Th17/Treg imbalance in patients with low-active systemic lupus erythematosus. Postepy Hig Med Dosw 2014; 68:893–898.

    Article  Google Scholar 

  3. Lu L, Barbi J, Pan F, Daniel C, Reuter S, Steulten C. The regulation of immune tolerance by FOXP3. Nat Rev Immunol 2017; 17:703–717.

    Article  CAS  Google Scholar 

  4. Valencia X, Yarboro C, Illei G, Lipsky PE, Yarboro C, Illei G. Deficient CD4, CD25 high T regulatory cell function in patients with active systemic lupus erythematosus. J Immunol 2007; 178:2579–2588.

    Article  CAS  Google Scholar 

  5. Wang X, Wang W, Xu J, Wu S, Le Q, Parizot C. All-trans retinoid acid promotes allogeneic corneal graft survival in mice by regulating Treg-Th17 balance in the presence of TGF-β. BMC Immunol 2015; 16:17.

    Article  Google Scholar 

  6. Hochberg MC, for the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthritis Rheum 1997; 1725:40.

    Google Scholar 

  7. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang DH, Mahadevan S and the Committee on Prognosis Studies in SLE. Derivation of the SLEDAI: a disease activity index for lupus patients. Arthritis Rheum 1992; 35:630–640.

    Article  CAS  Google Scholar 

  8. Crichton N, Wewers ME, Lowe NK, Liang S, Li J, Napierata L. A critical review of visual Analogue scales in the measurement of clinical phenomena. Black well Science Ltd. J Clin Nurs 2001; 10:697–706.

    Google Scholar 

  9. Tang G. Techniques for measuring vitamin A activity from β-carotene. Am J Clin Nutr 2012; 96:1185–1188.

    Article  Google Scholar 

  10. Furr HC, Green MH, Haskell M, Mokhtar N, Nestel P, Newton S, et al. Stable isotope dilution techniques for assessing vitamin A status and bio efficacy of provitamin A carotenoids in humans. Public Health Nutri 2005; 8:596–607.

    Article  Google Scholar 

  11. Morton RF, Hebel JR, McCarter RJ. [electronic resource], A study guide to epidemiology and biostatistics. 5th ed. Rockville: Md Aspen Publication; 2001. pp. 71–74.

    Google Scholar 

  12. Pan X, Yuan X, Zheng Y, Wang W, Shan J, Lin F, et al. Increased CD45RA+FoxP3low regulatory T cells with impaired suppressive function in patients with systemic lupus erythematosus. PLoS One 2012; 7:e34662.

    Article  CAS  Google Scholar 

  13. Kida Y, Xia Z, Zheng S, Mordwinkin NM, Louie SG, Zheng SG, et al. Interleukin-1 as an injury signal mobilizes retinyl esters in hepatic stellate Cells through down regulation of lecithin retinol acyltransferase. PLoS One 2011; 6:e26644.

    Article  CAS  Google Scholar 

  14. D’Ambrosio DN, Clugston RD, Blaner WS, Tao X, Cai L, Wang J. Vitamin A metabolism: an update. Nutrients 2011; 3:63–103.

    Article  Google Scholar 

  15. Hanly JG, Thompson K, McCurdy G, Fougere L, Theriault C, Wilton K. Measurement of autoantibodies using multiplex methodology in patients with systemic lupus erythematosus. J Immunol Methods 2010; 352:147–152.

    Article  CAS  Google Scholar 

  16. Elias K, Laurence A, Davidson TS, Stephens G, Kanno Y, Shevach EM, et al. Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood 2008; 111:1013–1020.

    Article  CAS  Google Scholar 

  17. Nolting J, Daniel C, Reuter S, Steulten C, Li P, Sucov H, et al. Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines. J Exp Med 2009; 206:2131–2139.

    Article  CAS  Google Scholar 

  18. Sobel ES, Brusko TM, Butfiloski EJ, Hou W, Li S, Cuda CM, et al. Defective response of CD4+ T cells to retinoic acid and TGF-β in systemic lupus erythematosus. Arthritis Res Ther 2011; 13:R106.

    Article  CAS  Google Scholar 

  19. Bennet RT, Mazzaccaro RJ, Chopta N, Melman A, Franco I, Soylu A, et al. Suppression of renal inflammation with vitamins A in lupus nephritis in SLE patients. J Urol 1999; 161:1681–1684.

    Article  Google Scholar 

  20. Yang J, Yang X, Zou H, Chu Y, Li M, Zou H. Recovery of the immune balance between Th17 and regulatory T cells as a treatment for systemic lupus erythematosus. Rheumatology 2011; 50:1366–1372.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dina S. Fettouh.

Additional information

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fettouh, D.S., Saif, D.S., El Gazzar, S.F. et al. Study the relationship between vitamin A deficiency, T helper 17, regulatory T cells, and disease activity in patients with systemic lupus erythematosus. Egypt Rheumatol Rehabil 46, 244–250 (2019). https://doi.org/10.4103/err.err_5_19

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/err.err_5_19

Keywords