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Vitamin D def...

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Conclusion
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Competing interests
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Arthritis Research & Therapy
Volume 10
Issue 6

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Highly AccessEditorial
Vitamin D or hormone D deficiency in autoimmune rheumatic diseases,
including undifferentiated connective tissue disease
===================================================================

Maurizio Cutolo email
Research Laboratory and Acadenic Clinical Unit of Rheumatology
department of Internal Medicine, University of Genova, Viale Bnedetto
XV, 6 161 32 Genova, Italy

author email corresponding author email
Arthritis Research & Therapy 2008, 10:123doi:10.1186/ar2552

See related research article by Zold et al.,
http://arthritis-research.com/content/10/5/R123
The electronic version of this article is the complete one and can be
found online at: http://arthritis-research.com/content/10/6/123

Published:
  1. December 2008
© 2008 BioMed Central Ltd

Abstract
Epidemiological evidence indicates a significant association between
vitamin D deficiency and an increased incidence of autoimmune
diseases. The presence of vitamin D receptors in the cells of the
immune system and the fact that several of these cells produce the
vitamin D hormone suggested that vitamin D could have immunoregulatory
properties, and now potent immuno-mudulatory activities on dendritic
cells, Th1 and Th17 cells, as well as B cells have been confirmed.
Patients with undifferentiated connective tissue disease also show
vitamin D deficiency and, interestingly, patients who progress into
connective tissue diseases have lower vitamin D levels than those who
remain in the undifferentiated connective tissue disease stage.

Vitamin D deficiency and autoimmune diseases
The recent study by Zold and colleagues 1 reports that a seasonal
variance in levels of 25(OH)D3 was identified in patients with
undifferentiated connective tissue disease (UCTD) and showed that
these levels were, in any case, significantly lower than in controls
during the corresponding seasons. The results showed also that more
severe vitamin D deficiency in UCTD patients may play a role in the
subsequent progress into well-defined connective tissue diseases
(CTDs).

Epidemiological evidence indicates a significant association between
vitamin D deficiency and an increased incidence of autoimmune diseases
2. Serum levels of vitamin D have been found to be significantly
lower in patients with systemic lupus erythematosus (SLE) and type-1
diabetes mellitus than in the healthy population 3. In addition, it
was also found that lower levels of vitamin D were associated with
higher disease activity in rheumatoid arthritis 4. An inverse
correlation has been described between the supplementation of vitamin
D and the development of type-1 diabetes mellitus and multiple
sclerosis 5.
Low serum levels of vitamin D3 might be partially related, among other
factors, to prolonged daily darkness (reduced activation of
pre-vitamin D by ultraviolet B sunlight), different genetic
backgrounds (that is, vitamin D receptor polymorphism) and nutritional
factors, and could explain the latitude-related prevalence of
autoimmune diseases such as rheumatoid arthritis (RA) when considering
the potential immunosuppressive roles of vitamin D 2.

Vitamin D or hormone D?
The term vitamin D is, unfortunately, an imprecise term, referring to
one or more members of a group of steroid molecules (seco-steroids).
The A, B, C, and D ring structure is derived from the
cyclopentanoperhydrophenanthrene ring structure of steroids. In
particular, seco-steroids are those in which one of the rings has been
broken 2.

Vitamin D, also known as cholecalciferol, is mainly generated in the
skin of animals when one of the rings of the precursor molecule
7-dehydrocholesterol has been broken by ultraviolet B light (UV-B, sun
light). Vitamin D (or hormone D) is thus not a true vitamin, because
individuals with adequate exposure to sunlight do not require dietary
supplementation. Although vitamin D is consumed in food, dietary
intake alone is often insufficient, supplying only 20% of the body's
requirements 2. Finally, the liver and kidney help convert vitamin D
to its active hormone forms (vitamin D3 hormone).
There is increasing evidence that steroid hormones (vitamins D2 and
D3) derived from vitamin D act through classic nuclear receptors
(nuclear vitamin D receptors (VDRs)), as well as specific binding
sites on the plasma membrane of target cells that are coupled to
signal transduction systems. Clarification of the physiological role
of endogenous VDR agonists in the regulation of autoimmune responses
will support the pharmacological VDR agonists for use in the clinic 6.
The antiproliferative, prodifferentiative, immunomodulatory and
anti-inflammatory properties of synthetic VDR agonists could be
exploited to treat a variety of autoimmune rheumatic diseases.

Vitamin D3 produces biological responses as a consequence of its
metabolism into 1α,25(OH)2-vitamin D3 (1,25(OH)2D3) and
24R,25(OH)2-vitamin D3. The metabolic production of these two
seco-steroids and their generation of a plethora of biological actions
that are attributable to the parent vitamin D3 are orchestrated via
the integrated operation of the hormone D endocrine system 6. This
system is very similar in its organization to that of classic
endocrine systems and is characterized by an endocrine gland (the
kidney, the source of the two steroid hormones), target cells that
possess receptors for the steroid hormones, and a feed-back loop
involving changes in serum calcium that alter the secretion of
parathyroid hormone (a stimulator of the renal 1-hydroxylase), which
modulates the output of the D steroid by the kidney 7.
Vitamin D hormone and the immune response

In recent years, the discovery of the VDR in the cells of the immune
system and the fact that several of these cells produce vitamin D
hormone suggested that vitamin D could have immunoregulatory
properties. VDR agonists seem primarily to inhibit dendritic cell
differentiation, and pathogenic pro-inflammatory T cells, such as Th1
and Th17 cells, and, under appropriate conditions, they seem to
promote a deviation to the Th2 pathway 2. In addition, two types of
cells are induced by 1,25(OH)2D3, the T regulatory cells (Tregs) and
the natural killer T cells; induction of these regulatory cells and
direct inhibition of Th1 cells are the mechanisms by which 1,25(OH)2D3
suppresses experimental autoimmunity 8.
Clearly, topical hormone D analogs are efficient in modulating skin
immune response in psoriasis 9. In addition, vitamin D may play an
important role in the maintenance of B cell homeostasis and the
correction of vitamin D deficiency may be useful in the treatment of B
cell-mediated autoimmune rheumatic disorders such as SLE 10. The
hormone D immunomodulatory and anti-inflammatory activities might be
particularly efficient in RA patients and support a therapeutic role
of 1,25(OH)2D3 in such disease.

Conclusion
The new study by Zold and colleagues reporting that, during the
average 2.3 year follow-up period, 21.7% of patients with UCTD and a
deficiency of vitamin D metabolites (hormone D) further developed well
established autoimmune CTD is of great interest 1. Patients who
progressed into CTDs had lower vitamin D levels than those who
remained in the UCTD stage and UCTD most frequently progressed into
RA, SLE, Sjögren's syndrome and mixed connective tissue disease 1.
Therefore, vitamin D hormone deficiency is also confirmed in UCTD and
might represent a new possible risk factor for the progression into
well defined autoimmune rheumatic diseases.

Abbreviations
1,25(OH)2D3: 1α, 25(OH)2-vitamin D3; CTD: connective tissue disease;
RA: rheumatoid arthritis; SLE: systemic lupus erythematosus; UCTD:
undifferentiated connective tissue disease; VDR: vitamin D receptor.

Competing interests
The author declares that they have no competing interests.

References
1. 

Zold E, Szodoray P, Gaal J, Kappelmayer J, Csathy L, Gyimesi E,
Zeher M, Szegedi G, Bodolay E: Vitamin D deficiency in
undifferentiated connective tissue disease.
Arthritis Res Ther 2008, 10:R123. PubMed Abstract  BioMed Central
Full Text  PubMed Central Full Text OpenURL

2. 
Cutolo M: Vitamin D and autoimmune rheumatic diseases.

Rheumatology 2008, in press. PubMed Abstract  Publisher Full Text
OpenURL
3. 

Cutolo M, Otsa K: Review: vitamin D, immunity and lupus.
Lupus 2008, 17:6-10. PubMed Abstract  Publisher Full Text OpenURL

4. 
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 Abstract  Publisher
Full Text OpenURL
5. 

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. PubMed Abstract  Publisher Full
Text OpenURL

6. 
Adorini A, Penna G: Control of autoimmune diseases by the vitamin
D endocrine system.

Nat Clin Pract Rheumatol 2008, 4:404-412. PubMed Abstract 
Publisher Full Text OpenURL
7. 

Norman AW, Henry HL, Bishop JE, Song XD, Bula , Okamura WH:
Different shapes of the steroid hormone 1α, 25(OH)2-vitamin D3 act
as agonists for two different receptors in the vitamin D endocrine
system to mediate genomic and rapid responses.
Steroids 2001, 66:147-158. PubMed Abstract  Publisher Full Text
OpenURL

8. 
Adams JS, Hewison M: Unexpected actions of vitamin D: new
perspectives on the regulation of innate and adaptive immunity.

Nat Clin Pract Endocrinol Metab 2008, 4:80-90. PubMed Abstract 
Publisher Full Text OpenURL
9. 

Sigmundsdottir H, an J, Debes GF, Alt C, Habtezion A, Soler D,
Butcher EC: DCs metabolize sunlight-induced vitamin D3 to
'program' T cell attraction to the epidermal chemokine CCL27.
Nat Immunol 2007, 8:285-293. PubMed Abstract  Publisher Full Text
OpenURL

10. 
Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE: Modulatory
effects of 1,25-dihydroxyvitamin D3 on human B cell
differentiation.

J Immunol 2007, 179:1634-1647. PubMed Abstract  Publisher Full
Text OpenURL
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