The Role of Vitamin D in Allergy

and Autoimune Diseases

Eko E. Surachmanto

Allergy and Immunology Division

Medical Faculty Sam Ratulangi University/
Prof. dr.R.D. Kandou Hospital, Manado
INTRODUCTION
➢ Vitamin D, or cholecalciferol, is a steroidal hormone whose main
function is the regulation of calcium homeostasis, and bone
Vitamins
formation chemically unrelatedthrough
and rearbsorption families of
theorganic compounds
interaction with the
that are essential
parathyroid in small
glands, amounts
kidneys, for normal metabolism
and bowel.

➢Vitamins
Current (with
studies
the have related
exception vitaminD)Dcannot
of vitamin deficiency with several
be synthesized
byautoimmune
humans  disorders,
need to be including
ingestedinsulin-
in the dependent diabetes
diet to prevent
mellitus of(IDDM),
disorders multiple sclerosis (MS), inflammatory bowel
metabolism
disease
Vitamin (IBD), systemic
divided lupus erythematosus
into water-soluble (SLE), and rheumatoid
& lipid-soluble
arthritis (RA)

Marques et.al. Review The importance of Vit.D levels in autoimmune disease.2009

Vitamin D metabolism and physiology
Vitamin D Deficiency Or Resistance Is Caused by One Of 4 Mechanisms

• Impaired availability of Vit D  secondary to inadequate dietary Vit D, fat

malabsorptive disorders, and/or lack of photoisomerization
• Impaired hydroxylation by the liver to produce 25-hydroxyvitamin D
• Impaired hydroxylation by the kidneys to produce 1,25-dihydroxyvitamin D
• End organ insensitivity to Vit D metabolites (hereditary Vit D resistant rickets)

Low Vitamin D status Correlates with disease bone & skeletal disease, cardiovascular, cancer, infections,
autoimmunity & immune mediated disease
Sources of Vitamin D
 Hypothesis
Accelerated Decrease In Population Serum 25D Caused By :
• Decreased Cutaneus Syntesis Of Vitamin D3
• Decreased Ingestion Of Vit D-fortified Foods
• Increased Storage Of Vitamin D In Fat Stores
• Failure To Mobilize Stored Vitamin D From Fat
 Causes of Vitamin D Deficiency
• Not consuming the recommended levels of the vitamin over
time
• Exposure to sunlight is limited
• Having dark skin
• Kidneys cannot convert vitamin D to its active form
• Digestive tract can not adequately absorb Vitamin D
• Obese
Vitamin D and Immune System

Vitamin D can improve and inhibit

OVER 900 IL-4 Production by T-cells
genes are
Fact: in adaptive immune system
regulated by
T-cell increasing and modifies the
Vitamin D function of antigen-presenting cells)
Autoimmune Diseases are Correlated with ;

25 (OH) D3 Vitamin D
serum Intake

VDR
UV Exposure
Polymorphism
The Immunomodulatory Effects of Vitamin D
on Immune Cells

Yang CY, et. Al. Clinic Rev Allerg Immunol 2016-013-8361-3

Vitamin D and Asthma
↑ Serum Vitamin
D

↑ Lung maturity
↓ Viral ↑ Steroid
↓ Atopy and
infections Responsiveness
development

↓ Asthma Morbidity

↑ Lung Function ↓ Healthcare utilization ↓ Asthma Exacerbation

Vitamin D and Asthma / Allergic
Pathogenesis Maintaining
mucosal
barrier
function

Inhibits
Promotes of
Proinflamatory VITAMIN D Cathelicidin
cytokines

Regulator of
adaptive
immunity
 Maintaining Mucosal Barrier
Vitamin D
Increase the airway smooth muscle and reduce lung
function
Maintaining mucosal barrier function  enhanced
expression of genes encoding epithelial tight junction
protein (Z)-1, claudin 1, claudin 2, and E-cadherin.
Inhibits Proinflamatory Cytokines
Vitamin D3 (VD3) receptor
is found in several cell types within immune system
(macrophages, APCs, Th1, Th2, and regulatory CD4+ T cells)

Inhibits IL2, IL17, and interferon γ

secreted by T cells and B cells and
attenuates cytotoxic activity and
proliferation of T cells and B cells
REGULATOR ADAPTIVE IMMUNITY
Vitamin D
can improve and inhibit IL-4 Production by T-
cells
Fact:
in adaptive immune system 
T-cell increasing and modifies the function of APCs
 Promotes of cathelicidin production
Cathelicidin encodes for the only
antimicrobial peptide produced by human

Have some role in innate

immune defense against
invasive bacterial infection
Low vitamin D & SLE : chicken or egg ?
Significant lower serum 25 hydroxyvitamin D levels
were observed in SLE patients

Trigger the disease

Aggravate immune aberration
Perpetuate disease activity

Low 25 (OH)D3 SLE activity /

level manifestations

• Avoidance of sun shine

• Sun Protection
• Lack of out door activities
• Renal Insufficiency
• Chronic used of medications
• Anti Vitamin D Antibodies
 Autoimmune Disease
Vitamin D insufficiency in:
–50% of pts w/ fibromyalgia + SLE
• Huisman et al. J Rheumatol. 2001;28(11):2535.
–58% Japanese F’s with Graves Disease
• Yamashita et al. Endocr J. 2001;48(1):63.
–73% Austrian pts w/ Ankylosing Spondilitis
• Falkenbach et al. Wien Klin Wochenschr. 2001;113(9):328
–Rheumatoid Arthtritis
• Cantorna.Proc Soc Exp Biol Med. 2000;223(3):230
 MONITORING
• 25-oh-vit D Levels & Serum Calcium
• Re-check Every 2-4 Months When Starting
With Levels Below 35ng/Ml
• Re-check Every 1-2 Months When Levels
over 35ng/ml Until Levels Plateau.
• Consider Continuing Age-appropriate
Supplementing With Infrequent Monitoring
How to measure
• 25 OH Vitamin D
• Don’t Measure 1,25 Vitamin D
• Calcium Or PTH
– Consider In Severe Deficiency
 Vitamin D dalam Darah (Manado)
11

Adekuat
Defisiensi
349
Insufficien
485

N= 845
 Treatment & Prevention Strategies

• We Suggest That All Adults Who Are Vitamin D Deficient 

Treated With 50,000 IU Of Vit D2
• Or Vit D3 Once A Week For 8 Wk
• Or Its Equivalent Of 6000 IU Of Vitamin D2
• Or Vitamin D3 Daily To Achieve A Blood Level Of 25 (OH)D Above
Ng/Ml, Followed By Maintenance Therapy Of 1500-2000 IU/D
(An Endocrine Society Clinical Practice Guidelie)
THANK YOU