Skip to main content

Advertisement

SpringerLink
Log in

Trace Elements Associated with Systemic Lupus Erythematosus and Insulin Resistance

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of multifactorial origin. Studies have shown that trace elements such as zinc and copper may help maintain optimum function of the immune system and metabolism, while toxic metals such as lead may increase systemic autoimmunity. The current study aimed to assess the relationship between serum concentration of lithium (Li), vanadium (V), copper (Cu), zinc (Zn), molybdenum (Mo), cadmium (Cd), and lead (Pb) and SLE diagnosis, disease activity measured by SLE disease activity index (SLEDAI) and insulin resistance (IR). This case-control, cross-sectional study included 225 patients, 120 healthy controls, and 105 SLE patients. Serum concentration of Li, V, Cu, Zn, Mo, Cd, and Pb was measured. Serum concentrations of V (p < 0.001), Zn (p < 0.001), and Pb (p < 0.001) were lower and Mo (p < 0.001) and Li (p < 0.001) were higher in patients with SLE compared to healthy controls. SLE diagnosis was associated with higher serum Li (p < 0.001) concentration and lower V (p < 0.001), Zn (p = 0.003), and Pb (p = 0.020). Toxic metals and trace elements were not associated with disease activity. Levels of Cd were higher in patients with IR (p = 0.042). There was no significant association between IR and the other metals. The results indicate that SLE patients have different profiles of trace elements and toxic metals compared to healthy controls. While some toxic metals and trace elements were found to be associated with SLE diagnosis, they had no effect on disease activity and IR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kamen DL (2014) Environmental influences on systemic lupus erythematosus expression. Rheum Dis Clin N Am 40:401–412. https://doi.org/10.1016/j.rdc.2014.05.003

    Article  Google Scholar 

  2. McMahon M, Hahn BH, Skaggs BJ (2011) Systemic lupus erythematosus and cardiovascular disease: prediction and potential for therapeutic intervention. Expert Rev Clin Immunol 7:227–241. https://doi.org/10.1586/eci.10.98

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tsokos GC (2011) Systemic lupus erythematosus. N Engl J Med 365:2110–2121. https://doi.org/10.1056/NEJMra1100359

    Article  CAS  PubMed  Google Scholar 

  4. Chowdhury B, Chandra R (1987) Biological and health implications of toxic heavy metal and essential trace element interactions. Prog Food Nutr Sci 11:55–113

    CAS  PubMed  Google Scholar 

  5. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ (2012) Heavy metals toxicity and the environment. EXS 101:133–164. https://doi.org/10.1007/978-3-7643-8340-4_6

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gilbert KM, Rowley B, Gomez-Acevedo H, Blossom SJ (2011) Coexposure to mercury increases immunotoxicity of trichloroethylene. Toxicol Sci 119:281–292. https://doi.org/10.1093/toxsci/kfq345

    Article  CAS  PubMed  Google Scholar 

  7. Hudson C, Cao L, Kasten-Jolly J, Kirkwood J, Lawrence D (2003) Susceptibility of lupus-prone Nzm mouse strains to lead exacerbation of systemic lupus erythematosus symptoms. J Toxicol Environ Health A 66:895–918. https://doi.org/10.1080/15287390306456

    Article  CAS  PubMed  Google Scholar 

  8. Leffel EK, Wolf C, Poklis A, White KL (2003) Drinking water exposure to cadmium, an environmental contaminant, results in the exacerbation of autoimmune disease in the murine model. Toxicology 188:233–250

    Article  CAS  PubMed  Google Scholar 

  9. Durak I, Kavutcu M, Canbolaţ O et al (1994) Concentrations of some major and minor elements in larynx tissues with and without cancer. Biometals 7:45–48

    Article  CAS  PubMed  Google Scholar 

  10. Taysi S, Gulcin I, Sari RA, Kuskay S, Bakan N (2003) Trace elements and disease activity score in patients with rheumatoid arthritis. Pain Clin 15:435–439. https://doi.org/10.1163/156856903770196827

    Article  Google Scholar 

  11. Prasad AS (2007) Zinc: mechanisms of host defense. J Nutr 137:1345–1349

    Article  CAS  PubMed  Google Scholar 

  12. Prasad AS (2009) Zinc: role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care 12:646–652. https://doi.org/10.1097/MCO.0b013e3283312956

    Article  CAS  PubMed  Google Scholar 

  13. Ho E, Courtemanche C, Ames BN (2003) Zinc deficiency induces oxidative DNA damage and increases p53 expression in human lung fibroblasts. J Nutr 133:2543–2548

    Article  CAS  PubMed  Google Scholar 

  14. Ferns GAA, Lamb DJ, Taylor A (1997) The possible role of copper ions in atherogenesis: the blue Janus. Atherosclerosis 133:139–152. https://doi.org/10.1016/S0021-9150(97)00130-5

    Article  CAS  PubMed  Google Scholar 

  15. Sahebari M, Abrishami-Moghaddam M, Moezzi A, Ghayour-Mobarhan M, Mirfeizi Z, Esmaily H, Ferns G (2014) Association between serum trace element concentrations and the disease activity of systemic lupus erythematosus. Lupus 23:793–801. https://doi.org/10.1177/0961203314530792

    Article  CAS  PubMed  Google Scholar 

  16. Marikovsky M, Ziv V, Nevo N, Harris-Cerruti C, Mahler O (2003) Cu/Zn superoxide dismutase plays important role in immune response. J Immunol 170:2993–3001

    Article  CAS  PubMed  Google Scholar 

  17. Panchal SK, Wanyonyi S, Brown L (2017) Selenium, vanadium, and chromium as micronutrients to improve metabolic syndrome. Curr Hypertens Rep 19:10. https://doi.org/10.1007/s11906-017-0701-x

    Article  CAS  PubMed  Google Scholar 

  18. Kucharz EJ, Sierakowski SJ, Goodwin JS (1993) Lithium in vitro enhances interleukin-2 production by T cells from patients with systemic lupus erythematosus. Immunopharmacol Immunotoxicol 15:515–523. https://doi.org/10.3109/08923979309019728

    Article  CAS  PubMed  Google Scholar 

  19. Federmann M, Morell B, Graetz G, Wyss M, Elsner P, von Thiessen R, Wuthrich B, Grob D (1994) Hypersensitivity to molybdenum as a possible trigger of ANA-negative systemic lupus erythematosus. Ann Rheum Dis 53:403–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wiernsperger N, Rapin J (2010) Trace elements in glucometabolic disorders: an update. Diabetol Metab Syndr 2:70. https://doi.org/10.1186/1758-5996-2-70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chunhabundit R (2016) Cadmium exposure and potential health risk from foods in contaminated area, Thailand. Toxicol Res 32:65–72. https://doi.org/10.5487/TR.2016.32.1.065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Miyake CNH, Gualano B, Dantas WS, Pereira RT, Neves W, Zambelli VO, Shinjo SK, Pereira RM, Silva ER, Sá-Pinto AL, Borba E, Roschel H, Bonfá E, Benatti FB (2018) Increased insulin resistance and glucagon levels in mild/inactive systemic lupus erythematosus patients despite normal glucose tolerance. Arthritis Care Res 70:114–124. https://doi.org/10.1002/acr.23237

    Article  CAS  Google Scholar 

  23. Chung CP, Avalos I, Oeser A, Gebretsadik T, Shintani A, Raggi P, Michael Stein C (2007) High prevalence of the metabolic syndrome in patients with systemic lupus erythematosus: association with disease characteristics and cardiovascular risk factors. AnnRheumDis 66:208–214. https://doi.org/10.1136/ard.2006.054973

    Article  CAS  Google Scholar 

  24. Lozovoy M, Simão A, Oliveira S, Iryioda TMV, Panis C, Cecchini R, Dichi I (2013) Relationship between iron metabolism, oxidative stress, and insulin resistance in patients with systemic lupus erythematosus. Scand J Rheumatol 42:303–310. https://doi.org/10.3109/03009742.2012.754942

    Article  CAS  PubMed  Google Scholar 

  25. Lozovoy M, Simão A, Morimoto H, Iryioda TMV, Panis C, Reiche EMV, Borelli SD, Oliveira SR, Cecchini R, Dichi I (2014) Hypertension is associated with serologically active disease in patients with systemic lupus erythematosus: role of increased Th1/Th2 ratio and oxidative stress. Scand J Rheumatol 43:59–62. https://doi.org/10.3109/03009742.2013.834963

    Article  CAS  PubMed  Google Scholar 

  26. Yu C, Gershwin ME, Chang C (2014) Diagnostic criteria for systemic lupus erythematosus: a critical review. J Autoimmun 48–49:10–13. https://doi.org/10.1016/j.jaut.2014.01.004

    Article  CAS  PubMed  Google Scholar 

  27. Bombardier C, Gladman D, Urowitz M et al (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum 35:630–640

    Article  CAS  PubMed  Google Scholar 

  28. Petri M, Genovese M, Engle E, Hochberg M (1991) Definition, incidence, and clinical description of flare in systemic lupus erythematosus: a prospective cohort study. Arthritis Rheum 34:937–944

    Article  CAS  PubMed  Google Scholar 

  29. Reilly M, Wolfe M, Rhodes T et al (2004) Measures of insulin resistance add incremental value to the clinical diagnosis of metabolic syndrome in association with coronary atherosclerosis. Circulation 110:803–809

    Article  CAS  PubMed  Google Scholar 

  30. International Conference On Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use; ICH Harmonized Tripartite Guideline, Validation of Analytical Procedures: Text and Methodology Q2(R 1), Complementary Guideline on Methodology dated 06 November 1996, incorporated in November 2005, London

  31. Yilmaz A, Sari RA, Gundogdu M, Kose N, Dag E (2005) Trace elements and some extracellular antioxidant proteins levels in serum of patients with systemic lupus erythematosus. Clin Rheumatol 24:331–335. https://doi.org/10.1007/s10067-004-1028-y

    Article  PubMed  Google Scholar 

  32. Tóth CN, Baranyai E, Csípő I, Tarr T, Zeher M, Posta J, Fábián I (2017) Elemental analysis of whole and protein separated blood serum of patients with systemic lupus erythematosus and Sjögren’s syndrome. Biol Trace Elem Res 179:14–22. https://doi.org/10.1007/s12011-017-0945-y

    Article  CAS  PubMed  Google Scholar 

  33. Nossent J, Lester S, Rischmueller M, Zalewski P (2017) No zinc deficiency but a putative immunosuppressive role for labile Zn in patients with systemic autoimmune disease. Curr Rheumatol Rev 13:59–64. https://doi.org/10.2174/1573397111666151026223501

    Article  CAS  PubMed  Google Scholar 

  34. Caetano MC, Ortiz TT, Terreri MTSLR et al (2009) Inadequate dietary intake of children and adolescents with juvenile idiopathic arthritis and systemic lupus erythematosus. J Pediatr 85:509–515. https://doi.org/10.2223/JPED.1941

    Article  Google Scholar 

  35. Strickland FM, Hewagama A, Wu A, Sawalha AH, Delaney C, Hoeltzel MF, Yung R, Johnson K, Mickelson B, Richardson BC (2013) Diet influences expression of autoimmune associated genes and disease severity by epigenetic mechanisms in a transgenic lupus model. Arthritis Rheum 65:1872–1881. https://doi.org/10.1002/art.37967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Prasad A (2008) Zinc in human health: effect of zinc on immune cells. Mol Med 14:353–357. https://doi.org/10.2119/2008-00033.Prasad

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dardenne M (2002) Zinc and immune function. Eur J Clin Nutr 56:S20–S23. https://doi.org/10.1038/sj.ejcn.1601479

    Article  CAS  PubMed  Google Scholar 

  38. Beck FW, Prasad AS, Kaplan J, Fitzgerald JT, Brewer GJ (1997) Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. Am J Phys 272:E1002–E1007. https://doi.org/10.1152/ajpendo.1997.272.6.E1002

    Article  CAS  Google Scholar 

  39. Timmer RT, Sands JM (1999) Lithium intoxication. JASN 10:666–674

    CAS  PubMed  Google Scholar 

  40. Shapiro HS (1998) Psychiatric side effects of medicines used in SLE. In: Aladjem H (ed) The challenges of lupus: insights and hope, 1st edn. Avery Publishing Group, New York, p 167

    Google Scholar 

  41. Liossis SNC, Kovacs B, Dennis G et al (1996) B cells from patients with systemic lupus erythematosus display abnormal antigen receptor-mediated early signal transduction events. J Clin Invest 98:2549–2557. https://doi.org/10.1172/JCI119073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. De Sarno P, Axtell RC, Raman C et al (2008) Lithium prevents and ameliorates experimental autoimmune encephalomyelitis. J Immunol 181:338–345

    Article  PubMed  Google Scholar 

  43. Tsave O, Petanidis S, Kioseoglou E, Yavropoulou MP, Yovos JG, Anestakis D, Tsepa A, Salifoglou A (2016) Role of vanadium in cellular and molecular immunology: association with immune-related inflammation and pharmacotoxicology mechanisms. Oxidative Med Cell Longev 2016:1–10. https://doi.org/10.1155/2016/4013639

    Article  CAS  Google Scholar 

  44. Ustarroz-Cano M, Garcia-Pelaez I, Cervantes-Yepez S, Lopez-Valdez N, Fortoul TI (2017) Thymic cytoarchitecture changes in mice exposed to vanadium. J Immunotoxicol 14:9–14. https://doi.org/10.1080/1547691X.2016.1250848

    Article  CAS  PubMed  Google Scholar 

  45. Campbell CA, Peet M, Ward NI (1988) Vanadium and other trace elements in patients taking lithium. Biol Psychiatry 24:775–781. https://doi.org/10.1016/0006-3223(88)90253-3

    Article  CAS  PubMed  Google Scholar 

  46. Waterman SJ, El-Fawal HAN, Snyder CA (1994) Lead alters the immunogenicity of two neural proteins: a potential mechanism for the progression of lead-induced neurotoxicity. Environ Health Perspect 102:1052–1056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. El-Fawal HAN, Waterman SJ, De Feo A, Shamy MY (1999) Neuroimmunotoxicology: humoral assessment of neurotoxicity and autoimmune mechanisms. Environ Health Perspect 107:767–775. https://doi.org/10.1289/ehp.99107s5767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ramírez-Sandoval R, Luévano-Rodríguez N, Rodríguez-Rodríguez M, Pérez-Pérez ME, Saldívar-Elias S, Gurrola-Carlos R, Avalos-Díaz E, Bollain-y-Goytia JJ, Herrera-Esparza R (2015) An animal model using metallic ions to produce autoimmune nephritis. J Immunol Res 2015:1–11. https://doi.org/10.1155/2015/269610

    Article  CAS  Google Scholar 

  49. Drehmer M, Odegaard AO, Schmidt MI, Duncan BB, Cardoso LO, Matos SMA, Molina MCB, Barreto SM, Pereira MA (2017) Brazilian dietary patterns and the dietary approaches to stop hypertension (DASH) diet-relationship with metabolic syndrome and newly diagnosed diabetes in the ELSA-Brasil study. Diabetol Metab Syndr 9:13. https://doi.org/10.1186/s13098-017-0211-7

    Article  PubMed  PubMed Central  Google Scholar 

  50. Mugabo Y, Li L, Renier G (2010) The connection between C-reactive protein (CRP) and diabetic vasculopathy. Focus on preclinical findings. Curr Diabetes Rev 6:27–34. https://doi.org/10.2174/157339910790442628

    Article  CAS  PubMed  Google Scholar 

  51. Lin Y, Rathod D, Ho W, Caffrey J (2009) Cadmium exposure is associated with elevated blood C-reactive protein and fibrinogen in the U. S. Population: the third national health and nutrition examination survey (NHANES III, 1988-1994). Ann Epidemiol 19:592–596. https://doi.org/10.1016/j.annepidem.2009.02.005

    Article  CAS  PubMed  Google Scholar 

  52. Colacino JA, Arthur AE, Ferguson KK, Rozek LS (2014) Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress. Environ Res 131:6–12. https://doi.org/10.1016/j.envres.2014.02.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bui VQ, Stein AD, DiGirolamo AM et al (2012) Associations between serum C-reactive protein and serum zinc, ferritin, and copper in Guatemalan school children. Biol Trace Elem Res 148:154–160. https://doi.org/10.1007/s12011-012-9358-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ghayour-Mobarhan M, Taylor A, New S, Lamb DJ, Ferns GAA (2005) Determinants of serum copper, zinc and selenium in healthy subjects. Ann Clin Biochem 42:364–375. https://doi.org/10.1258/0004563054889990

    Article  CAS  PubMed  Google Scholar 

  55. Bo S, Gambino R, Berutti C, Milanesio N, Caropreso A, Gentile L, Cassader M, Cavallo-Perin P, Pagano GDM (2008) Associations of dietary and serum copper with inflammation, oxidative stress, and metabolic variables in adults. J Nutr 138:305–310

    Article  CAS  PubMed  Google Scholar 

  56. Bigazzi PE (1994) Autoimmunity and heavy metals. Lupus 3:449–453

    Article  CAS  PubMed  Google Scholar 

  57. Parker B, Bruce I (2013) SLE and metabolic syndrome. Lupus 22:1259–1266. https://doi.org/10.1177/0961203313502570

    Article  CAS  PubMed  Google Scholar 

  58. Morel L (2017) Immunometabolism in systemic lupus erythematosus. Nat Rev Rheumatol 13:280–290. https://doi.org/10.1038/nrrheum.2017.43

    Article  CAS  PubMed  Google Scholar 

  59. Perl A, Hanczko R, Lai ZW, Oaks Z, Kelly R, Borsuk R, Asara JM, Phillips PE (2015) Comprehensive metabolome analyses reveal N-acetylcysteine-responsive accumulation of kynurenine in systemic lupus erythematosus: implications for activation of the mechanistic target of rapamycin. Metabolomics 11:1157–1174. https://doi.org/10.1007/s11306-015-0772-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yin Y, Choi S-C, Xu Z, Perry DJ, Seay H, Croker BP, Sobel ES, Brusko TM, Morel L (2015) Normalization of CD4 + T cell metabolism reverses lupus. Sci Transl Med 7:274ra18. https://doi.org/10.1126/scitranslmed.aaa0835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Sobel ES, Brusko TM, Butfiloski EJ, Hou W, Li S, Cuda CM, Abid AN, Reeves WH, Morel L (2011) Defective response of CD4(+) T cells to retinoic acid and TGFβ in systemic lupus erythematosus. Arthritis Res Ther 13:R106. https://doi.org/10.1186/ar3387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Jacobs SR, Herman CE, Maciver NJ et al (2008) Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways. J Immunol 180:4476–4486

    Article  CAS  PubMed  Google Scholar 

  63. Peretz A, Neve J, Famaey J (1989) Effects of chronic and acute corticosteroid therapy on zinc and copper status in rheumatoid arthritis patients. J Trace Elem Electrolytes Health Dis 3:103–108

    CAS  PubMed  Google Scholar 

  64. Haga HJ, Brun JG, Rekvig OP, Wetterberg L (1999) Seasonal variations in activity of systemic lupus erythematosus in a subarctic region. Lupus 8:269–273. https://doi.org/10.1191/096120399678847858

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by Laboratory of Atomic Emission Spectrometry (LAES) from State University of Londrina- Parana State, Brazil.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Londrina, Londrina, Paraná, Brazil

    Eliel Marcio Pedro

  2. Research Laboratory of Applied Immunology, University of Londrina, Paraná, Brazil

    Lorena Flor da Rosa Franchi Santos & Bruna Miglioranza Scavuzzi

  3. Department of Rheumatology, Pontifícia Universidade Católica, PUC, Londrina, Paraná, Brazil

    Tatiana Mayumi Veiga Iriyoda & Andréa Name Colado Simão

  4. Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Rua Robert Koch, n 60, Londrina, Paraná, Brazil

    Tiago Severo Peixe, Marcell Alysson Batiste Lozovoy, Edna Maria Vissoci Reiche, Andréa Name Colado Simão & Maria Josefa Santos

  5. Department of Internal Medicine, University of Londrina, Londrina, Paraná, Brazil

    Isaias Dichi

Authors
  1. Eliel Marcio Pedro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lorena Flor da Rosa Franchi Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bruna Miglioranza Scavuzzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tatiana Mayumi Veiga Iriyoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tiago Severo Peixe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marcell Alysson Batiste Lozovoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Edna Maria Vissoci Reiche
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Isaias Dichi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andréa Name Colado Simão
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maria Josefa Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andréa Name Colado Simão.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pedro, E.M., da Rosa Franchi Santos, L.F., Scavuzzi, B.M. et al. Trace Elements Associated with Systemic Lupus Erythematosus and Insulin Resistance. Biol Trace Elem Res 191, 34–44 (2019). https://doi.org/10.1007/s12011-018-1592-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-018-1592-7

Keywords

Search

Navigation