Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 5/2008

Open Access 01-10-2008 | Research article

Vitamin D deficiency in undifferentiated connective tissue disease

Authors: Eva Zold, Peter Szodoray, Janos Gaal, János Kappelmayer, Laszlo Csathy, Edit Gyimesi, Margit Zeher, Gyula Szegedi, Edit Bodolay

Published in: Arthritis Research & Therapy | Issue 5/2008

Login to get access

Abstract

Introduction

Both experimental and clinical data provide evidence that vitamin D is one of those important environmental factors that can increase the prevalence of certain autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory bowel disease. The aim of the present study was to investigate the prevalence of vitamin D insufficiency in patients with undifferentiated connective tissue disease (UCTD).

Methods

Plasma 25(OH)D3 levels in 161 UCTD patients were measured in both summer and winter periods. Autoantibody profiles (antinuclear antibody, anti-U1-ribonucleoprotein, anti-SSA, anti-SSB, anti-Jo1, anti-Scl70, anti-double-stranded DNA, anti-centromere, anti-cardiolipin, rheumatoid factor, and anti-cyclic citrullinated peptide) and clinical symptoms of the patients were assessed.

Results

Plasma levels of 25(OH)D3 in UCTD patients were significantly lower compared with controls in both summer and winter periods (UCTD summer: 33 ± 13.4 ng/mL versus control: 39.9 ± 11.7 ng/mL, P = 0.01; UCTD winter: 27.8 ± 12.48 ng/mL versus control: 37.8 ± 12.3 ng/mL, P = 0.0001). The presence of dermatological symptoms (photosensitivity, erythema, and chronic discoid rash) and pleuritis was associated with low levels of vitamin D. During the average follow-up period of 2.3 years, 35 out of 161 patients (21.7%) with UCTD further developed into well-established connective tissue disease (CTD). Patients who progressed into CTDs had lower vitamin D levels than those who remained in the UCTD stage (vitamin D levels: CTD: 14.7 ± 6.45 ng/mL versus UCTD: 33.0 ± 13.4 ng/mL, P = 0.0001).

Conclusions

In patients with UCTD, a seasonal variance in levels of 25(OH)D3 was identified and showed that these levels were significantly lower than in controls during the corresponding seasons. Our results suggest that vitamin D deficiency in UCTD patients may play a role in the subsequent progression into well-defined CTDs.
Appendix
Available only for authorised users
Literature
1.
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. 10.1046/j.1525-1373.2000.22333.x.CrossRefPubMed
2.
Griffin MD, Lutz WH, Phan VA, Bachman LA, McKean DJ, Kumar R: Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs. Biochem Biophys Res Commun. 2000, 270: 701-708. 10.1006/bbrc.2000.2490.CrossRefPubMed
3.
Hayes CE, Nashold FE, Spach KM, Pedersen LB: The immunological functions of the vitamin D endocrine system. Cell Mol Biol (Noisy-le-grand). 2003, 49: 277-300.
4.
Lips P: Which circulating level of 25-hydroxyvitamin D is appropriate?. J Steroid Biochem Mol Biol. 2004, 89–90: 611-614. 10.1016/j.jsbmb.2004.03.040.CrossRefPubMed
5.
Nagpal S, Na S, Rathnachalam R: Noncalcemic actions of vitamin D receptor ligands. Endocr Rev. 2005, 26: 662-687. 10.1210/er.2004-0002.CrossRefPubMed
6.
Patel S, Farragher T, Berry J, Bunn D, Silman A, Symmons D: Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis. Arthritis Rheum. 2007, 56: 2143-2149. 10.1002/art.22722.CrossRefPubMed
7.
Penna G, Adorini L: 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol. 2000, 164: 2405-2411.CrossRefPubMed
8.
Berer A, Stockl J, Majdic O, Wagner T, Kollars M, Lechner K, Geissler K, Oehler L: 1,25-Dihydroxyvitamin D(3) inhibits dendritic cell differentiation and maturation in vitro. Exp Hematol. 2000, 28: 575-583. 10.1016/S0301-472X(00)00143-0.CrossRefPubMed
9.
van Etten E, Mathieu C: Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005, 97: 93-101. 10.1016/j.jsbmb.2005.06.002.CrossRefPubMed
10.
Daniel C, Sartory NA, Zahn N, Radeke HH, Stein JM: Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther. 2008, 324: 23-33. 10.1124/jpet.107.127209.CrossRefPubMed
11.
Cantorna MT, Mahon BD: Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med (Maywood). 2004, 229: 1136-1142.
12.
Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM: Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001, 358: 1500-1503. 10.1016/S0140-6736(01)06580-1.CrossRefPubMed
13.
Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS: Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev. 2006, 5: 114-117. 10.1016/j.autrev.2005.05.009.CrossRefPubMed
14.
Littorin B, Blom P, Scholin A, Arnqvist HJ, Blohme G, Bolinder J, Ekbom-Schnell A, Eriksson JW, Gudbjornsdottir S, Nystrom L, Ostman J, Sundkvist G: Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS). Diabetologia. 2006, 49: 2847-2852. 10.1007/s00125-006-0426-x.CrossRefPubMed
15.
Ruiz-Irastorza G, Egurbide MV, Olivares N, Martinez-Berriotxoa A, Aguirre C: Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatology (Oxford). 2008, 47: 920-923. 10.1093/rheumatology/ken121.CrossRef
16.
Bodolay E, Csiki Z, Szekanecz Z, Ben T, Kiss E, Zeher M, Szucs G, Danko K, Szegedi G: Five-year follow-up of 665 Hungarian patients with undifferentiated connective tissue disease (UCTD). Clin Exp Rheumatol. 2003, 21: 313-320.PubMed
17.
Mosca M, Tani C, Neri C, Baldini C, Bombardieri S: Undifferentiated connective tissue diseases (UCTD). Autoimmun Rev. 2006, 6: 1-4. 10.1016/j.autrev.2006.03.004.CrossRefPubMed
18.
Mosca M, Tani C, Bombardieri S: Undifferentiated connective tissue diseases (UCTD): a new frontier for rheumatology. Best Pract Res Clin Rheumatol. 2007, 21: 1011-1023. 10.1016/j.berh.2007.09.004.CrossRefPubMed
19.
Mosca M, Tavoni A, Neri R, Bencivelli W, Bombardieri S: Undifferentiated connective tissue diseases: the clinical and serological profiles of 91 patients followed for at least 1 year. Lupus. 1998, 7: 95-100. 10.1191/096120398678919787.CrossRefPubMed
20.
Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980, 23: 581-590. 10.1002/art.1780230510.
21.
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002/art.1780310302.CrossRefPubMed
22.
Bohan A, Peter JB: Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975, 292: 344-347.CrossRefPubMed
23.
Fox RI, Robinson CA, Curd JG, Kozin F, Howell FV: Sjogren's syndrome. Proposed criteria for classification. Arthritis Rheum. 1986, 29: 577-585. 10.1002/art.1780290501.CrossRefPubMed
24.
Alarcón-Segovia D, Villareal M: Classification and diagnostic criteria for classification of mixed connective tissue disease. Mixed Connective Tissue Disease and Antinuclear Antibodies. Edited by: Toyo T, Miyawaki S. 1987, Elsevier: Amsterdam, 33-40.
25.
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982, 25: 1271-1277. 10.1002/art.1780251101.CrossRefPubMed
26.
Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N: The diagnosis of osteoporosis. J Bone Miner Res. 1994, 9: 1137-1141.CrossRefPubMed
27.
Hollis BW: Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005, 135: 317-322.PubMed
28.
Hollis BW, Wagner CL: Normal serum vitamin D levels. N Engl J Med. 2005, 352: 515-516. 10.1056/NEJM200502033520521.PubMed
29.
30.
Cantorna MT, Zhu Y, Froicu M, Wittke A: Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr. 2004, 80: 1717S-1720S.PubMed
31.
Grant WB: Epidemiology of disease risks in relation to vitamin D insufficiency. Prog Biophys Mol Biol. 2006, 92: 65-79. 10.1016/j.pbiomolbio.2006.02.013.CrossRefPubMed
32.
Lips P: Vitamin D physiology. Prog Biophys Mol Biol. 2006, 92: 4-8. 10.1016/j.pbiomolbio.2006.02.016.CrossRefPubMed
33.
Vieth R: What is the optimal vitamin D status for health?. Prog Biophys Mol Biol. 2006, 92: 26-32. 10.1016/j.pbiomolbio.2006.02.003.CrossRefPubMed
34.
Bhattoa HP, Bettembuk P, Ganacharya S, Balogh A: Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women. Osteoporos Int. 2004, 15: 447-451. 10.1007/s00198-003-1566-1.CrossRefPubMed
35.
Cutolo M, Otsa K, Laas K, Yprus M, Lehtme R, Secchi ME, Sulli A, Paolino S, Seriolo B: Circannual vitamin d serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe. Clin Exp Rheumatol. 2006, 24: 702-704.PubMed
36.
Cutolo M, Otsa K, Uprus M, Paolino S, Seriolo B: Vitamin D in rheumatoid arthritis. Autoimmun Rev. 2007, 7: 59-64. 10.1016/j.autrev.2007.07.001.CrossRefPubMed
37.
Tetlow LC, Woolley DE: The effects of 1 alpha,25-dihydroxyvitamin D(3) on matrix metalloproteinase and prostaglandin E(2) production by cells of the rheumatoid lesion. Arthritis Res. 1999, 1: 63-70. 10.1186/ar12.PubMedCentralCrossRefPubMed
38.
Bamford CR, Sibley WA, Thies C: Seasonal variation of multiple sclerosis exacerbations in Arizona. Neurology. 1983, 33: 697-701.CrossRefPubMed
39.
Embry AF, Snowdon LR, Vieth R: Vitamin D and seasonal fluctuations of gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol. 2000, 48: 271-272. 10.1002/1531-8249(200008)48:2<271::AID-ANA28>3.0.CO;2-O.CrossRefPubMed
40.
Munger KL, Zhang SM, O'Reilly E, Hernan MA, Olek MJ, Willett WC, Ascherio A: Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004, 62: 60-65.CrossRefPubMed
41.
Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG: Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study. Arthritis Rheum. 2004, 50: 72-77. 10.1002/art.11434.CrossRefPubMed
42.
Andreassen H, Rix M, Brot C, Eskildsen P: Regulators of calcium homeostasis and bone mineral density in patients with Crohn's disease. Scand J Gastroenterol. 1998, 33: 1087-1093. 10.1080/003655298750026804.CrossRefPubMed
43.
O'Regan S, Chesney RW, Hamstra A, Eisman JA, O'Gorman AM, DeLuca HF: Reduced serum 1,25-(OH)2 vitamin D3 levels in prednisone-treated adolescents with systemic lupus erythematosus. Acta Paediatr Scand. 1979, 68: 109-111. 10.1111/j.1651-2227.1979.tb04969.x.CrossRefPubMed
44.
Müller K, Kriegbaum NJ, Baslund B, Sorensen OH, Thymann M, Bentzen K: Vitamin D3 metabolism in patients with rheumatic diseases: low serum levels of 25-hydroxyvitamin D3 in patients with systemic lupus erythematosus. Clin Rheumatol. 1995, 14: 397-400. 10.1007/BF02207671.CrossRefPubMed
45.
Szodoray P, Nakken B, Barath S, Gaal J, Aleksza M, Zeher M, Sipka S, Szilagyi A, Zold E, Szegedi G, Bodolay E: Progressive divergent shifts in natural and induced T-regulatory cells signify the transition from undifferentiated to definitive connective tissue disease. Int Immunol. 2008, 20: 971-979. 10.1093/intimm/dxn056.CrossRefPubMed
46.
Carvalho JF, Blank M, Kiss E, Tarr T, Amital H, Shoenfeld Y: Anti-vitamin D, vitamin D in SLE: preliminary results. Ann N Y Acad Sci. 2007, 1109: 550-557. 10.1196/annals.1398.061.CrossRefPubMed
47.
Adorini L: Selective immunointervention in autoimmune diseases: lessons from multiple sclerosis. J Chemother. 2001, 13: 219-234.CrossRefPubMed
48.
Adorini L: Immunomodulatory effects of vitamin D receptor ligands in autoimmune diseases. Int Immunopharmacol. 2002, 2: 1017-1028. 10.1016/S1567-5769(02)00049-8.CrossRefPubMed
Metadata
Title
Vitamin D deficiency in undifferentiated connective tissue disease
Authors
Eva Zold
Peter Szodoray
Janos Gaal
János Kappelmayer
Laszlo Csathy
Edit Gyimesi
Margit Zeher
Gyula Szegedi
Edit Bodolay
Publication date
01-10-2008
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 5/2008
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2533

Other articles of this Issue 5/2008

Arthritis Research & Therapy 5/2008 Go to the issue

Erratum

Erratum to: Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus

Review

Targeting histone deacetylase activity in rheumatoid arthritis and asthma as prototypes of inflammatory disease: should we keep our HATs on?

Erratum

Erratum to: Forced mobilization accelerates pathogenesis: characterization of a preclinical surgical model of osteoarthritis

Research article

Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis

Review

Genetic studies in osteoporosis – the end of the beginning

Review

Developments in the scientific and clinical understanding of gout
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits