Circulating levels of free 25(OH)D increase at the onset of rheumatoid arthritis


Autoři: Vidyanand Anaparti aff001;  Xiaobo Meng aff001;  Mahadevappa Hemshekhar aff001;  Irene Smolik aff001;  Neeloffer Mookherjee aff001;  Hani El-Gabalawy aff001
Působiště autorů: Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada aff001;  Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, Canada aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0219109

Souhrn

Objective

Epidemiological studies suggest vitamin D deficiency as a potential risk factor for rheumatoid arthritis (RA) development, a chronic autoimmune disorder highly prevalent in indigenous North American (INA) population. We therefore profiled the circulating levels of 25-hydroxyvitaminD [25(OH)D], an active metabolite of vitamin D, in a cohort of at-risk first-degree relatives (FDR) of INA RA patients, a subset of whom subsequently developed RA (progressors).

Methods

2007 onward, serum samples from INA RA patients and FDR were collected at the time of a structured baseline visit and stored at -20°C. Anti-citrullinated protein antibodies (ACPA), 25(OH)D, hs-CRP, vitamin-D binding protein (VDBP) and parathyroid hormone (PTH) levels were determined using ELISA and rheumatoid factor (RF) seropositivity was determined by nephelometry.

Results

We demonstrate that 25 (OH) D concentrations were lower in winter than summer (P = 0.0538), and that serum 25(OH)D levels were higher in samples collected and stored after 2013 (P<0.0001). Analysis of samples obtained after 2013 demonstrated that 37.6% of study participants were 25(OH)D insufficient (<75nmol/L). Also, seropositive RA patients and FDR had lower 25(OH)D levels compared to ACPA-/FDR (P<0.05, P<0.01 respectively). Linear regression analysis showed 25(OH)D insufficiency was inversely associated with presence of RA autoantibodies. Longitudinal samples from 14 progressors demonstrated a consistent increase in 25(OH)D levels at the time they exhibited clinically detectable joint inflammation, without any significant change in VDBP or PTH levels. Spearman rank correlation analysis showed significant association between 25(OH)D and PTH levels, both in RA patients and progressors at RA onset time.

Conclusion

We demonstrate that 25(OH)D levels in serum increased at RA onset in progressors. The potential role that vitamin D metabolites and their downstream effects play in RA transition requires further investigation.

Klíčová slova:

Enzyme-linked immunoassays – Medical risk factors – Rheumatoid arthritis – Specimen storage – Summer – Vitamin D – Winter – Parathyroid hormone


Zdroje

1. Hurd K, Barnabe C. Mortality causes and outcomes in Indigenous populations of Canada, the United States, and Australia with rheumatic disease: A systematic review. Semin Arthritis Rheum. 2018;47(4):586–92. doi: 10.1016/j.semarthrit.2017.07.009 28823732.

2. Deane KD, Demoruelle MK, Kelmenson LB, Kuhn KA, Norris JM, Holers VM. Genetic and environmental risk factors for rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2017;31(1):3–18. doi: 10.1016/j.berh.2017.08.003 29221595; PubMed Central PMCID: PMC5726551.

3. Deane KD, El-Gabalawy H. Pathogenesis and prevention of rheumatic disease: focus on preclinical RA and SLE. Nat Rev Rheumatol. 2014;10(4):212–28. doi: 10.1038/nrrheum.2014.6 24514912; PubMed Central PMCID: PMC4090326.

4. Anaparti V, Smolik I, Meng X, Spicer V, Mookherjee N, El-Gabalawy H. Whole blood microRNA expression pattern differentiates patients with rheumatoid arthritis, their seropositive first-degree relatives, and healthy unrelated control subjects. Arthritis Res Ther. 2017;19(1):249. doi: 10.1186/s13075-017-1459-x 29126434; PubMed Central PMCID: PMC5681796.

5. Deane KD. Preclinical Rheumatoid Arthritis and Rheumatoid Arthritis Prevention. Curr Rheumatol Rep. 2018;20(8):50. doi: 10.1007/s11926-018-0754-0 29946747.

6. Shapira Y, Agmon-Levin N, Shoenfeld Y. Geoepidemiology of autoimmune rheumatic diseases. Nat Rev Rheumatol. 2010;6(8):468–76. doi: 10.1038/nrrheum.2010.86 20567251.

7. Sparks JA, Karlson EW. The Roles of Cigarette Smoking and the Lung in the Transitions Between Phases of Preclinical Rheumatoid Arthritis. Curr Rheumatol Rep. 2016;18(3):15. doi: 10.1007/s11926-016-0563-2 26951253; PubMed Central PMCID: PMC4941234.

8. Bellan M, Sainaghi PP, Pirisi M. Role of Vitamin D in Rheumatoid Arthritis. Adv Exp Med Biol. 2017;996:155–68. doi: 10.1007/978-3-319-56017-5_13 29124698.

9. Lin J, Liu J, Davies ML, Chen W. Serum Vitamin D Level and Rheumatoid Arthritis Disease Activity: Review and Meta-Analysis. PLoS One. 2016;11(1):e0146351. doi: 10.1371/journal.pone.0146351 26751969; PubMed Central PMCID: PMC4709104.

10. Bragazzi NL, Watad A, Neumann SG, Simon M, Brown SB, Abu Much A, et al. Vitamin D and rheumatoid arthritis: an ongoing mystery. Curr Opin Rheumatol. 2017;29(4):378–88. doi: 10.1097/BOR.0000000000000397 28463872.

11. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol Rev. 2016;96(1):365–408. doi: 10.1152/physrev.00014.2015 26681795; PubMed Central PMCID: PMC4839493.

12. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29(6):726–76. doi: 10.1210/er.2008-0004 18694980; PubMed Central PMCID: PMC2583388.

13. Hayes CE, Hubler SL, Moore JR, Barta LE, Praska CE, Nashold FE. Vitamin D Actions on CD4(+) T Cells in Autoimmune Disease. Front Immunol. 2015;6:100. doi: 10.3389/fimmu.2015.00100 25852682; PubMed Central PMCID: PMC4364365.

14. El-Gabalawy HS, Robinson DB, Smolik I, Hart D, Elias B, Wong K, et al. Familial clustering of the serum cytokine profile in the relatives of rheumatoid arthritis patients. Arthritis Rheum. 2012;64(6):1720–9. doi: 10.1002/art.34449 22354869.

15. El-Gabalawy HS, Robinson DB, Hart D, Elias B, Markland J, Peschken CA, et al. Immunogenetic risks of anti-cyclical citrullinated peptide antibodies in a North American Native population with rheumatoid arthritis and their first-degree relatives. J Rheumatol. 2009;36(6):1130–5. doi: 10.3899/jrheum.080855 19411392.

16. Tanner S, Dufault B, Smolik I, Meng X, Anaparti V, Hitchon C, et al. A prospective study of the development of inflammatory arthritis in the family members of Indigenous North American people with rheumatoid arthritis. Arthritis Rheumatol. 2019. doi: 10.1002/art.40880 30861615.

17. Hanley DA, Cranney A, Jones G, Whiting SJ, Leslie WD, Cole DE, et al. Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada. CMAJ. 2010;182(12):E610–8. doi: 10.1503/cmaj.080663 20624868; PubMed Central PMCID: PMC2934850.

18. Bikle DD, Malmstroem S, Schwartz J. Current Controversies: Are Free Vitamin Metabolite Levels a More Accurate Assessment of Vitamin D Status than Total Levels? Endocrinol Metab Clin North Am. 2017;46(4):901–18. doi: 10.1016/j.ecl.2017.07.013 29080642; PubMed Central PMCID: PMC5675107.

19. Zerwekh JE. The measurement of vitamin D: analytical aspects. Ann Clin Biochem. 2004;41(Pt 4):272–81. doi: 10.1258/0004563041201464 15298739.

20. Agborsangaya C, Toriola AT, Grankvist K, Surcel HM, Holl K, Parkkila S, et al. The effects of storage time and sampling season on the stability of serum 25-hydroxy vitamin D and androstenedione. Nutr Cancer. 2010;62(1):51–7. doi: 10.1080/01635580903191460 20043259.

21. Piccolo BD, Hall LM, Stephensen CB, Gertz ER, Van Loan MD. Circulating 25-Hydroxyvitamin D Concentrations in Overweight and Obese Adults Are Explained by Sun Exposure, Skin Reflectance, and Body Composition. Curr Dev Nutr. 2019;3(7):nzz065. doi: 10.1093/cdn/nzz065 31304455; PubMed Central PMCID: PMC6616201.

22. Ashenafi S, Mazurek J, Rehn A, Lemma B, Aderaye G, Bekele A, et al. Vitamin D(3) Status and the Association with Human Cathelicidin Expression in Patients with Different Clinical Forms of Active Tuberculosis. Nutrients. 2018;10(6). doi: 10.3390/nu10060721 29867045; PubMed Central PMCID: PMC6024873.

23. Chow LN, Choi KY, Piyadasa H, Bossert M, Uzonna J, Klonisch T, et al. Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine model of collagen-induced arthritis. Mol Immunol. 2014;57(2):86–92. doi: 10.1016/j.molimm.2013.08.011 24091294.

24. Gombart AF. The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol. 2009;4(9):1151–65. doi: 10.2217/fmb.09.87 19895218; PubMed Central PMCID: PMC2821804.

25. Larcombe L, Mookherjee N, Slater J, Slivinski C, Dantouze J, Singer M, et al. Vitamin D, serum 25(OH)D, LL-37 and polymorphisms in a Canadian First Nation population with endemic tuberculosis. Int J Circumpolar Health. 2015;74(1):28952. doi: 10.3402/ijch.v74.28952 28417792.

26. Sall J, Carlsson M, Gidlof O, Holm A, Humlen J, Ohman J, et al. The antimicrobial peptide LL-37 alters human osteoblast Ca2+ handling and induces Ca2+-independent apoptosis. J Innate Immun. 2013;5(3):290–300. doi: 10.1159/000346587 23406612.

27. Wang Y, Zhang F, Wang S, Shang X, Luo S, Zhou H, et al. Serum Vitamin D Level is Inversely Associated With Anti-Cyclic Citrullinated Peptide Antibody Level and Disease Activity in Rheumatoid Arthritis Patients. Arch Rheumatol. 2016;31(1):64–70. doi: 10.5606/ArchRheumatol.2016.5556 29900980; PubMed Central PMCID: PMC5827868.

28. Liu Y, Wen H. Impact of vitamin D deficiency on clinical parameters in treatment-naive rheumatoid arthritis patients. Z Rheumatol. 2018;77(9):833–40. doi: 10.1007/s00393-018-0426-5 29460148.

29. Feser M, Derber LA, Deane KD, Lezotte DC, Weisman MH, Buckner JH, et al. Plasma 25,OH vitamin D concentrations are not associated with rheumatoid arthritis (RA)-related autoantibodies in individuals at elevated risk for RA. J Rheumatol. 2009;36(5):943–6. doi: 10.3899/jrheum.080764 19286844; PubMed Central PMCID: PMC2745328.

30. Hiraki LT, Arkema EV, Cui J, Malspeis S, Costenbader KH, Karlson EW. Circulating 25-hydroxyvitamin D level and risk of developing rheumatoid arthritis. Rheumatology (Oxford). 2014;53(12):2243–8. doi: 10.1093/rheumatology/keu276 25065001; PubMed Central PMCID: PMC4241892.

31. Hollis BW. Measuring 25-hydroxyvitamin D in a clinical environment: challenges and needs. Am J Clin Nutr. 2008;88(2):507S–10S. doi: 10.1093/ajcn/88.2.507S 18689391.

32. Langlois K, Greene-Finestone L, Little J, Hidiroglou N, Whiting S. Vitamin D status of Canadians as measured in the 2007 to 2009 Canadian Health Measures Survey. Health Rep. 2010;21(1):47–55. 20426226.

33. Weiler HA, Leslie WD, Krahn J, Steiman PW, Metge CJ. Canadian Aboriginal women have a higher prevalence of vitamin D deficiency than non-Aboriginal women despite similar dietary vitamin D intakes. J Nutr. 2007;137(2):461–5. doi: 10.1093/jn/137.2.461 17237327.

34. Larcombe L, Mookherjee N, Slater J, Slivinski C, Singer M, Whaley C, et al. Vitamin D in a northern Canadian first nation population: dietary intake, serum concentrations and functional gene polymorphisms. PLoS One. 2012;7(11):e49872. doi: 10.1371/journal.pone.0049872 23185470; PubMed Central PMCID: PMC3503822.

35. Hitchon CA, Sun Y, Robinson DB, Peschken CA, Bernstein CN, Siminovitch KA, et al. Vitamin D receptor polymorphism rs2228570 (Fok1) is associated with rheumatoid arthritis in North American natives. J Rheumatol. 2012;39(9):1792–7. doi: 10.3899/jrheum.120387 22859341.

36. Thacher TD, Levine MA. CYP2R1 mutations causing vitamin D-deficiency rickets. J Steroid Biochem Mol Biol. 2017;173:333–6. doi: 10.1016/j.jsbmb.2016.07.014 27473561.

37. Kagi L, Bettoni C, Pastor-Arroyo EM, Schnitzbauer U, Hernando N, Wagner CA. Regulation of vitamin D metabolizing enzymes in murine renal and extrarenal tissues by dietary phosphate, FGF23, and 1,25(OH)2D3. PLoS One. 2018;13(5):e0195427. doi: 10.1371/journal.pone.0195427 29771914; PubMed Central PMCID: PMC5957386.

38. Russo A, Biselli-Chicote PM, Kawasaki-Oyama RS, Castanhole-Nunes MMU, Maniglia JV, de Santi Neto D, et al. Differential Expression of Prostaglandin I2 Synthase Associated with Arachidonic Acid Pathway in the Oral Squamous Cell Carcinoma. J Oncol. 2018;2018:6301980. doi: 10.1155/2018/6301980 30532780; PubMed Central PMCID: PMC6250001.

39. Wamberg L, Christiansen T, Paulsen SK, Fisker S, Rask P, Rejnmark L, et al. Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss. Int J Obes (Lond). 2013;37(5):651–7. doi: 10.1038/ijo.2012.112 22828938.

40. Nishikawa M, Yasuda K, Takamatsu M, Abe K, Nakagawa K, Tsugawa N, et al. Generation of 1,25-dihydroxyvitamin D3 in Cyp27b1 knockout mice by treatment with 25-hydroxyvitamin D3 rescued their rachitic phenotypes. J Steroid Biochem Mol Biol. 2019;185:71–9. doi: 10.1016/j.jsbmb.2018.07.012 30031146.

41. Young KA, Munroe ME, Guthridge JM, Kamen DL, Niewold TB, Gilkeson GS, et al. Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus. Ann Rheum Dis. 2017;76(1):153–8. doi: 10.1136/annrheumdis-2016-209157 27283331; PubMed Central PMCID: PMC5360632.

42. Khundmiri SJ, Murray RD, Lederer E. PTH and Vitamin D. Compr Physiol. 2016;6(2):561–601. doi: 10.1002/cphy.c140071 27065162.


Článek vyšel v časopise

PLOS One


2019 Číslo 9

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Krvácení v důsledku portální hypertenze při jaterní cirhóze – od pohledu záchranné služby až po závěrečný hepato-gastroenterologický pohled
nový kurz
Autoři: PhDr. Petr Jaššo, MBA, MUDr. Hynek Fiala, Ph.D., prof. MUDr. Radan Brůha, CSc., MUDr. Tomáš Fejfar, Ph.D., MUDr. David Astapenko, Ph.D., prof. MUDr. Vladimír Černý, Ph.D.

Rozšíření možností lokální terapie atopické dermatitidy v ordinaci praktického lékaře či alergologa
Autoři: MUDr. Nina Benáková, Ph.D.

Léčba bolesti v ordinaci praktického lékaře
Autoři: MUDr. PhDr. Zdeňka Nováková, Ph.D.

Revmatoidní artritida: včas a k cíli
Autoři: MUDr. Heřman Mann

Jistoty a nástrahy antikoagulační léčby aneb kardiolog - neurolog - farmakolog - nefrolog - právník diskutují
Autoři: doc. MUDr. Štěpán Havránek, Ph.D., prof. MUDr. Roman Herzig, Ph.D., doc. MUDr. Karel Urbánek, Ph.D., prim. MUDr. Jan Vachek, MUDr. et Mgr. Jolana Těšínová, Ph.D.

Všechny kurzy
Kurzy Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se