*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
Streszczenie
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.
Summary
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.
Introduction
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).
Aim
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.
Results
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Piśmiennictwo
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