*Vladyslav Povoroznyuk1, Omelyan Synenky1, Nataliya Balatska2, Paweł Płudowski1, 3
Vitamin D status and disease activity in patients with rheumatoid arthritis
Witamina D i aktywność choroby u pacjentów z reumatoidalnym zapaleniem stawów
1State Institution “D. F. Chebotarev Institute of Gerontology”, NAMS Ukraine, Kiev, Ukraine
Head of Clinic: Professor Vladyslav Povoroznyuk, MD, PhD
2Lviv Regional Clinical Hospital, Lviv, Ukraine
Head of Clinic: Mykhailo Hyczka, MD, PhD
3Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children’s Memorial Health Institute, Warsaw
Head of Department: Professor Roman Janas, PhD
Wstęp. Witamina D stanowi istotny czynnik immunomodulacyjny, a rola deficytu witaminy D w patogenezie i przebiegu reumatoidalnego zapalenia stawów (RZS) nie jest ostatecznie zbadana.
Cel pracy. Głównym celem badania było określenie relacji pomiędzy stężeniem 25(OH)D w surowicy oraz aktywnością choroby u pacjentów z reumatoidalnym zapaleniem stawów (RZS).
Materiał i metody. Do badania włączono 93 pacjentów w wieku 27-80 lat, wśród badanych 74,2% stanowiły kobiety. Grupę kontrolną stanowiło 93 praktycznie zdrowych osób.
Wyniki. W ujęciu ogólnym 54,8% chorych na RZS ujawniło niedobór witaminy D, a 37,6% jej deficyt. Stężenia 25(OH)D były wyraźnie niższe u pacjentów z najwyższą aktywnością RZS w porównaniu z wartościami pacjentów z minimalną aktywnością RZS (16,55 ± 9,26 ng/ml vs. 22,59 ± 9,74 ng/ml; p < 0,05). Nie zaobserwowano istotnej różnicy między średnim stężeniem 25(OH)D pacjentów z RZS a grupą kontrolną. Odnotowano istotną ujemną zależność między stężeniem 25(OH)D a wskaźnikami aktywności choroby, która zwiększyła się po uwzględnieniu wieku, płci i BMI pacjentów RZS: DAS28-ESR (β = -0,33; 95% CI = -0,05; -0,01), CRP (β = -0,23; 95% CI = -0,72; 0,00) oraz ESR (β = -0,26; 95% CI = -0,78; -0,10). Niedobór witaminy D powinien być traktowany jako ważny czynnik prognostyczny dla wysokiej aktywności RZS (AUROC = 0,67; 95% CI = 0,513-0,83; p = 0,05).
Wnioski. W przebiegu RZS istotne jest uzyskanie i utrzymanie optymalnego zaopatrzenia w witaminę D.
Introduction. Vitamin D is a strong immunomodulator and the role of vitamin D deficiency in the pathogenesis of rheumatoid arthritis (RA) and the course of RA are still not well recognized.
Aim. The aim of the study was to describe the associations between serum level of 25-hydroxyvitamin D and disease activity in patients with rheumatoid arthritis (RA).
Material and methods. The study group comprised 93 patients aged 27-80 years suffering from RA (74.2% women) and 93 controls.
Results. In general, 54.8% of RA patients revealed vitamin D deficiency, and 37.6% – vitamin D insufficiency. No significant difference was found when mean serum 25(OH)D levels in RA patients and healthy controls where compared. 25(OH)D levels appeared markedly lower in patients with the highest activity of RA compared to values noted in patients with the minimal RA activity (16.55 ± 9.26 vs. 22.59 ± 9.74 ng/ml, p < 0.05). In RA patients 25(OH)D levels were significantly and negatively associated with markers of disease activity: DAS28-ESR (β = -0.33; 95% CI = 0.05; -0.01), CRP (β = -0.23; 95% CI = -0.72; 0.00), and ESR (β = -0.26; 95% CI = -0.78; -0.10). All these associations remained statistically significant after adjustment for gender, age and BMI. Vitamin D deficiency should be considered as an important predictor of the high RA activity (AUROC = 0.67; 95% CI = 0.513-0.83; p = 0.05).
Conclusions. Optimal vitamin D status should be obtained and maintained during RA course.
Taking into consideration that vitamin D deficiency is associated with an exacerbation of Th1-mediated immune response, the role of vitamin D deficiency in the pathogenesis of rheumatoid arthritis (RA), and the effect of vitamin D on the progress and treatment of RA are extensively examined (1-4).
RA is an autoimmune disease with a complex cascade of pathophysiological components. RA mainly affects the synovial membrane of the joints, which is infiltrated with neutrophils, macrophages, T and B lymphocytes, dendritic cells, all together leading to its gradual damage (5, 6). Despite numerous studies the causes of “abnormal” immune activation have not been established to date. However, the role of some risk factors playing an important role has been proven (7). In particular, the number of publications supporting the hypothesis that vitamin D deficiency affects the development of RA increases (8, 9). At present it is believed that calcitriol inhibits the processes of cartilage destruction by IL-1β-mediated production of matrix metalloproteinase and, therefore vitamin D deficiency can be regarded as one of the potential triggers of the cartilage destruction in RA (10).
Therefore the aim of the study was to describe the associations between serum level of 25-hydroxyvitamin D [25(OH)D] and disease activity in patients with rheumatoid arthritis.
Material and methods
93 patients with RA aged 27 to 80 yrs who were admitted to the rheumatology department of Lviv regional clinical hospital with exacerbation of RA were examined. The diagnosis of RA was made under classification criteria as defined by American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) (2010) (11), and Ukrainian adapted clinical guidelines “Rheumatoid arthritis” (2014) (12).
The research was conducted in October and November, 2015. The majority of RA patients in this study were females (74.2%). The mean age of male was (53.3 ± 12.1 yrs) was not different from that in female group (53.4 ± 11.2 yrs; p > 0.05). Patients with other inflammatory diseases, thyroid or parathyroid gland diseases, other endocrine disorders or serious liver or kidney diseases were excluded.
All the patients were diagnosed with the joint type of RA. 72 patients (77.4%) were diagnosed with seropositive type of RA. The average duration of disease was 8.6 ± 6.0 years.
Control group consisted of 93 practically healthy persons who took part in epidemiological study in Lviv region which was conducted in May and June 2010-2012.
All patients underwent clinical and biochemical blood test. The levels of rheumatoid factor (RF) and C-reactive protein (CRP) were measured by immunoturbidimetric assay. Anti-cyclic citrullinated peptide antibodies (A-CCP) were determined by flow cytometry. Erythrocyte sedimentation rate (ESR) was measured by Westergren method. DAS28-ESR was calculated using a formula that includes ESR value and the number of swollen and painful joints by the 28/28 scale (DAS28) (13, 14). The level of 25(OH)D in the serum was measured using electroluminescence method. The optimal vitamin D supply was defined when serum 25(OH)D level was 30-50 ng/ml, vitamin D insufficiency and deficiency were noted for 25(OH)D levels between 20-30 ng/ml and for 25(OH)D levels lower than 20 ng/ml, respectively (15).
This study was performed according to the principles of the Declaration of Helsinki and was approved by the Medical Ethics Committee of the Lviv Regional Clinical Hospital and State Institution “D. F. Chebotarev Institute of Gerontology” NAMS Ukraine. Each participant provided written informed consent.
Statistical analyzes were performed using software “Statistica 7.0” and SPSS version 17. The results are presented as the mean and standard deviation (M ± SD). The test for normality of distribution of the sampling was carried out by the Kolmogorov-Smirnov test. The subgroup differences were assessed by one-way ANOVA test adjusted by Scheffe. Univariable and multifactor linear regression models were used to determine the associations between 25(OH)D and outcome measures (markers of diseases activity) before and after adjustment for a age, sex and body mass index (BMI). Confidence interval (95% CI) was determined separately for each of these parameters. Receive operating characteristic (ROC) curves were used to determine the optimal vitamin D cutoff points for identifying disease activity. Youden’s index (J) was used to determine the optimal cutoff point. P value less than 0.05 was considered statistically significant.
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1. Wen H, Baker JF: Vitamin D, Immunoregulation, and Rheumatoid Arthritis. Journal of Clinical Rheumatology 2011; 17(2): 102-107.
2. Arnson Y, Amital H, Shoenfeld Y: Vitamin D and autoimmunity: new etiological and therapeutical considerations. Ann Rheum Dis 2007; 66: 1137-1142.
3. Di Rosa M, Malaguarnera M, Nicoletti F, Malaguarnera L: Vitamin D3: a helpful immunomodulator. Immunology 2011; 134: 123-139.
4. Hewison M: Vitamin D and the immune system: new perspectives on an old theme. Rheum Dis Clin North Am 2012; 38: 125-139.
5. Harris ED: Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med 1990; 322: 1277-1289.
6. Kim HR, Park MK, Cho ML et al.: Induction of macrophage migration inhibitory factor in ConA-stimulated rheumatoid arthritis synovial fibroblasts through the P38 map kinase dependent signaling pathway. Korean J Intern Med 2010; 25: 317-326.
7. Cutolo, M, Otsa K: Vitamin D, immunity and lupus. Lupus 2008; 17: 6-10.
8. Kiran G, Debashish D: Vitamin D and rheumatoid arthritis: is there a link? Int J Rheum Dis 2008; 11: 206-211.
9. Cantorna MT: Vitamin D and autoimmunity: is vitamin D status an environmental factor affecting autoimmune disease prevalence? Proc Soc Exp Biol Med 2000; 223: 230-233.
10. Tetlow LC, Wooley DE: The effects of 1,25-dihydroxyvitamin D3 on matrix metalloproteinase and prostaglandin E2 production by cells of the rheumatoid lesion. Arthritis Res 1999; 1: 63-70.
11. Aletaha D, Neogi T, Silman AJ et al.: 2010 rheumatoid arthritis classification criteria. An American College of Rheumatology, European League Against Rheumatism Collaborative Initiative. Arthritis & Rheumatism 2010; 9(62): 2569-2581.
12. ????? ? 263 ??? 11.04.2014 «??? ???????????? ??????????? ????????? ?????????, ?????????? ?? ??????? – ???????????? ??????».
13. Aletaha D, Ward MM, Machold KP et al.: Remission and active disease in rheumatoid arthritis: defining criteria for disease activity states. Arthritis and Rheumatism 2005; 52(9): 2625-2636.
14. The DAS28 Score. National Rheumatoid Arthritis Society; http://www.nras.org.uk/about_rheumatoid_arthritis/established_disease/managing_well/the_das28 _score.aspx (accessed: 11 September 2011).
15. Płudowski P, Karczmarewicz E, Bayer M et al.: Practical guidelines for supplementation of vitamin D and treatment of deficits in Central Europe: recommended vitamin D Intakes in general population and groups being at risk of vitamin D deficiency. Endokrynologia Pol 2013; 64(4): 120-127.
16. Hong Q, Xu J, Xu S et al.: Associations between serum 25-hydroxyvitamin D and disease activity, inflammatory cytokines and bone loss in patients with rheumatoid artritis. Rheumatology 2014; 53: 1994-2001.
17. Raczkiewicz A, Kisiel B, Kulig M, Tlustochowicz W: Vitamin d status and its association with quality of life, physical activity, and disease activity in rheumatoid arthritis patients. Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 2015; 21(3): 126-130.
18. Lin J, Liu J, Davies M, 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.
19. Patel S, Farragher T, Berry J et al.: Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis. Arthritis Rheum 2007; 56: 2143-2149.
20. Kroger H, Pentilla IM, Alhava EM: Low serum vitamin D metabolites in women with rheumatoid arthritis. Scand J Rheumatol 1993; 22: 172-177.
21. Haque UJ, Bartlett SJ: Relationships among vitamin D, disease activity, pain and disability in rheumatoid arthritis. Clin Exp Rheumatol 2010; 28: 745-747.
22. Azzeh FS, Kensara OA: Vitamin D Is a Good Marker for Disease Activity of Rheumatoid Arthritis Disease. Disease markers 2015; 260725. DOI: 10.1155/2015/260725.