Biological Trace Element Research

, Volume 189, Issue 2, pp 379–386 | Cite as

Serum Cesium, Rhenium, and Rubidium in Rheumatoid Arthritis Patients

  • Hussein Kadhem Al-HakeimEmail author
  • Shatha Rouf Moustafa
  • Khlowd Mohammed Jasem


A considerable attention has been focused on the possible association between ultra-trace elements (UTEs) status and pathogenesis of many diseases including rheumatoid arthritis (RA). UTEs have important roles in numerous metabolic processes. Serum Cs, Rb, and Re levels in RA are not studied previously. The correlation of serum Cs, Rb, and Re levels with the well-known serological parameters, anticyclic citrullinated protein antibody (ACPA), C-reactive protein (CRP), ESR, and rheumatoid factor (RF) is also not studied previously. The present study aimed to measure the level and the correlation between serum UTEs with various blood tests results in RA patients. Serum Cs, Rb, Re, ACPA, CRP, RF, and ESR were measured in Iraqi RA patients who have a positive ACPA (ACPA > 25 U/ml) and compared with healthy individuals. There were significant elevations (p < 0.05) in serum levels of all the measured parameters as compared with those of the healthy control group except Rb and uric acid which have not been changed. Subgrouping of patients according to the results of CRP and RF leads to different results. In the low-CRP group, the high-RF subgroup showed an elevation of ACPA, Cs, and ESR in comparison with the low-RF patients. In the high-CRP group, the patients with high RF showed an increase in the levels of Cs, Rb, ESR, and ACPA. The patient group with high RF and high CRP showed more significant correlations between serum UTEs and serological tests. Serum levels of UTEs were significantly altered in RA patients. The variations in the serum levels of the measured parameters in RA need more investigation to explore the possible association between these UTEs and RA. RA subgroups, according to the results of CRP and CPA, produce more and various information than taking RA as a whole group in the estimation of UTEs.


Rheumatoid arthritis Cesium Rubidium Rhenium ACPA 



The authors gratefully acknowledge the assistance of Dr. Duaa Hussein Al-Hakeim in drafting and editing the manuscript.

Compliance with Ethical Standards

Written consents were obtained from the patients and control groups. Ethical approval for this study was obtained from the Institutional Review Board of University of Kufa, Iraq.

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Schirmer M (2016) Immune system and rheumatic diseases in the elderly. Dtsch Med Wochenschr 141(11):794–796Google Scholar
  2. 2.
    Anandarajah AP (2011) Clinical aspects of rheumatoid arthritis: highlights from the 2010 ACR conference. Int J Clin Rheumatol 6(3):26772Google Scholar
  3. 3.
    Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, Pillemer SR, Reveille JD, Stone JH, National Arthritis Data Workgroup (2008) Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part I. Arthritis Rheum 58:15–25Google Scholar
  4. 4.
    Myasoedova E, Crowson C, Kremers HM, Therneau TM, Gabriel S (2010) Is the incidence of rheumatoid arthritis rising? Results from Olmsted County, Minnesota, 1955-2007. Arthritis Rheum 62:1576–1582Google Scholar
  5. 5.
    Alkazzaz AMH (2013) Incidence of rheumatoid arthritis (2001 to 2011). Iraqi Postgrad Med J 12(4):568–572Google Scholar
  6. 6.
    Hashmi GM, Shah MH (2012) Comparative assessment of essential and toxic metals in the blood of rheumatoid arthritis patients and healthy subjects. Biol Trace Elem Res 146(1):13–22Google Scholar
  7. 7.
    Mierzecki A, Strecker D, Radomska K (2011) A pilot study on zinc levels in patients with rheumatoid arthritis. Biol Trace Elem Res 143(2):854–862Google Scholar
  8. 8.
    Li J, Liang Y, Mao H, Deng W, Zhang J (2014) Effects of B-lymphocyte dysfunction on the serum copper, selenium and zinc levels of rheumatoid arthritis patients. Pak J Med Sci 30(5):1064–1067Google Scholar
  9. 9.
    Sahebari M, Ayati R, Mirzaei H, Sahebkar A, Hejazi S, Saghafi M, Saadati N, Ferns GA, Ghayour-Mobarhan M (2016) Serum trace element concentrations in rheumatoid arthritis. Biol Trace Elem Res 171(2):237–245Google Scholar
  10. 10.
    Yang TH, Yuan TH, Hwang YH, Lian IB, Meng M, Su CC (2016) Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper. J Formos Med Assoc 115(11):991–996Google Scholar
  11. 11.
    Afridi HI, Kazi TG, Brabazon D, Naher S (2012) Interaction between zinc, cadmium, and lead in scalp hair samples of Pakistani and Irish smokers rheumatoid arthritis subjects in relation to controls. Biol Trace Elem Res 148(2):139–147Google Scholar
  12. 12.
    Li WB, Klein W, Blanchardon E, Puncher M, Leggett RW, Oeh U, Breustedt B, Nosske D, Lopez MA (2015) Parameter uncertainty analysis of a biokinetic model of caesium. Radiat Prot Dosim 163(1):37–57Google Scholar
  13. 13.
    O'Brien CE, Harik N, James LP, Seib PM, Stowe CD (2008) Cesium-induced QT-interval prolongation in an adolescent. Pharmacotherapy: J Human Pharmacol Drug Ther 28(8):1059–1065Google Scholar
  14. 14.
    Harari F, Bottai M, Casimiro E, Palm B, Vahter M (2015) Exposure to lithium and cesium through drinking water and thyroid function during pregnancy: a prospective cohort study. Thyroid 25(11):1199–1208Google Scholar
  15. 15.
    Krachler M, Domej W (2001) Clinical laboratory parameters in osteoarthritic knee-joint effusions correlated to trace element concentrations. Biol Trace Elem Res 79(2):139–148Google Scholar
  16. 16.
    Stohs SJ, Bagchi D, Hassoun E, Bagchi M (2001) Oxidative mechanisms in the toxicity of chromium and cadmium ions. J Environ Pathol Toxicol Oncol 20:77–88Google Scholar
  17. 17.
    Sabeh F, Fox D, Weiss SJ (2010) Membrane type I matrix metalloproteinase-dependent regulation of rheumatoid arthritis synoviocyte function. J Immunol 184:6396–6406Google Scholar
  18. 18.
    McInnes LB, Schett G (2011) Mechanisms of disease: the pathogenesis of rheumatoid arthritis. N Engl J Med 365:2205–2219Google Scholar
  19. 19.
    Figueroa JA, Stiner CA, Radzyukevich TL, Heiny JA (2016) Metal ion transport quantified by ICP-MS in intact cells. Sci Rep 6:20551Google Scholar
  20. 20.
    Soetan KO, Olaiya CO, Oyewole OE (2010) The importance of mineral elements for humans, domestic animals and plants: a review. Afr J Food Sci 4(5):200–222Google Scholar
  21. 21.
    von Scholten BJ, Hasbak P, Christensen TE, Ghotbi AA, Kjaer A, Rossing P, Hansen TW (2016) Cardiac (82)Rb PET/CT for fast and non-invasive assessment of microvascular function and structure in asymptomatic patients with type 2 diabetes. Diabetologia 59(2):371–378Google Scholar
  22. 22.
    Hill JA, Bell DA, Brintnell W, Yue D, Wehrli B, Jevnikar AM, Lee DM, Hueber W, Robinson WH, Cairns E (2008) Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice. J Exp Med 205(4):967–979Google Scholar
  23. 23.
    Umeda N, Matsumoto I, Sumida T (2017) The pathogenic role of ACPA in rheumatoid arthritis. Nihon Rinsho Meneki Gakkai Kaishi 40(6):391–395Google Scholar
  24. 24.
    Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO et al (2010) 2010 rheumatoid arthritis classification criteria. An American College of Rheumatology/European League against Rheumatism Collaborative Initiative. Arthritis Rheum 62(9):2569–2581Google Scholar
  25. 25.
    Liu X, Piao J, Huang Z, Zhang SQ, Li W, Tian Y, Yang X (2014) Determination of 16 selected trace elements in children plasma from China economical developed rural areas using high resolution magnetic sector inductively coupled mass spectrometry. J Anal Methods Chem 2014(975820):1–6Google Scholar
  26. 26.
    Afridi HI, Kazi TG, Kazi N, Talpur FN, Shah F, Naeemullah et al (2013) Evaluation of status of arsenic, cadmium, lead and zinc levels in biological samples of normal and arthritis patients of age groups (46-60) and (61-75) years. Clin Lab 59(1–2):143–153Google Scholar
  27. 27.
    Xin L, Yang X, Cai G, Fan D, Xia Q, Liu L, Hu Y, Ding N, Xu S, Wang L, Li X, Zou Y, Pan F (2015) Serum levels of copper and zinc in patients with rheumatoid arthritis: a meta-analysis. Biol Trace Elem Res 168(1):1–10Google Scholar
  28. 28.
    Ullah Z, Ullah MI, Hussain S, Kaul H, Lone KP (2016) Determination of serum trace elements (Zn, Cu, and Fe) in Pakistani patients with rheumatoid arthritis. Biol Trace Elem Res 1–7Google Scholar
  29. 29.
    Ҫolak M, Bingöl NK, Ayhan O, Avci Ş, Bulut V (2001) Serum copper, zinc, and selenium levels in rheumatoid arthritis. Romatizma 16(2):66–71Google Scholar
  30. 30.
    Moyano MF, Mariño-Repizo L, Tamashiro H, Villegas L, Acosta M, Gil RA (2016) ICPMS analysis of proteins separated of metalloprotein profiles in human synovial fluid with acute and chronic arthritis. J Trace Elem Med Biol 36:44–51Google Scholar
  31. 31.
    Zoli A, Altomaonte L, Carcchio R, Galossi A, Ruffini MP (1998) Serum zinc, copper in active rheumatoid arthritis: correlation with interlukin 1β and tumor necrosis factor-α. Clin Rheumatol 17(5):378–382Google Scholar
  32. 32.
    Quiñonez-Flores CM, González-Chávez SA, Del Río ND, Pacheco-Tena C (2016) Oxidative stress relevance in the pathogenesis of the rheumatoid arthritis: a systematic review. Biomed Res Int 2016:6097417Google Scholar
  33. 33.
    Rao MR, Gopal SD (2015) C-reactive protein-a critical review. IntJCurrMicrobiolAppSci 4(12):55–61Google Scholar
  34. 34.
    Gupta A, Kaushik R, Kaushik RM, Saini M, Kakkar R (2014) Association of anti-cyclic citrullinated peptide antibodies with clinical and radiological disease severity in rheumatoid arthritis. Curr Rheumatol Rev 10(2):136–143Google Scholar
  35. 35.
    Seegobin SD, Ma MH, Dahanayake C, Cope AP, Scott DL, Lewis CM et al (2014) ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and corticosteroids: secondary analysis of a randomized controlled trial. Arthritis Res Ther 16(1):R13Google Scholar
  36. 36.
    Van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW (2005) Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther 7:R949–R958Google Scholar
  37. 37.
    Padyukov L, Seielstad M, Ong RT, Ding B, Ronnelid J, Seddighzadeh M et al (2011) Epidemiological investigation of rheumatoid arthritis study group: a genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis. Ann Rheum Dis 70:259–265Google Scholar
  38. 38.
    Daha NA, Toes RE (2011) Rheumatoid arthritis: are ACPA-positive and ACPA-negative RA the same disease? Nat Rev Rheumatol 7:202–203Google Scholar
  39. 39.
    Di Paolo ML, Scarpa M, Corazza A, Stevanato R, Rigo A (2002) Binding of cations of group IA and IIA to bovine serum amine oxidase: effect on the activity. Biophys J 83(4):2231–2239Google Scholar
  40. 40.
    Afridi HI, Kazi TG, Talpur FN, Naher S, Brabazon D (2014) Relationship between toxic metals exposure via cigarette smoking and rheumatoid arthritis. Clin Lab 60(10):1735–1745Google Scholar
  41. 41.
    Afridi HI, Talpur FN, Kazi TG, Brabazon D (2015) Estimation of toxic elements in the samples of different cigarettes and their effect on the essential elemental status in the biological samples of Irish smoker rheumatoid arthritis consumers. Environ Monit Assess 187(4):157–163Google Scholar
  42. 42.
    Karavida N, Notopoulos A (2010) Radiation synovectomy: an effective alternative treatment for inflamed small joints. Hippokratia 14(1):22–27Google Scholar
  43. 43.
    Shin CY, Son M, Ko JI, Jung MY, Lee IK, Kim SH et al (2003) DA-7911, 188Rhenium-tin colloid, as a new therapeutic agent of rheumatoid arthritis. Arch Pharm Res 26(2):168–172Google Scholar
  44. 44.
    Moustafa SR (2015) Clinical correlations between cesium, cobalt, manganese, rubidium and rhenium with the pathogenesis of rheumatoid arthritis. Sci J Clin Med 4(5):99–108Google Scholar
  45. 45.
    Goresky CA, Bach GG, Nadeau BE (1973) On the uptake of materials by the intact liver; the concentrative transport of rubidium-86. J Clin Invest 52(5):975–990Google Scholar
  46. 46.
    Milanick MA, Arnett KL (2002) Extracellular protons regulate the extracellular cation selectivity of the sodium pump. J Gen Physiol 120(4):497–408Google Scholar
  47. 47.
    Niedermeier W, Griggs JH (1971) Trace metal composition of synovial fluid and blood serum of patients with rheumatoid arthritis. J Chronic Dis 23(8):527–536Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Chemistry, Faculty of ScienceUniversity of KufaKufaIraq
  2. 2.Clinical Analysis Department, College of PharmacyHawler Medical UniversityHavalan CityIraq
  3. 3.Department of Chemistry, Faculty of ScienceKerbala UniversityKerbalaIraq

Personalised recommendations