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Clinical Review

Diagnosis and management of vitamin D deficiency

BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.b5664 (Published 11 January 2010) Cite this as: BMJ 2010;340:b5664

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Vitamin D deficiency - the commonest secondary immunodeficiency disorder?

The review by Professor Pearce and Dr Cheetham on vitamin D
deficiency is timely. The substantial public health problem imposed by
chronic vitamin D deficiency in our society has been known for some time
(1). Our diagnostic immunology service receives approximately 400 test
requests each week to measure serum vitamin D. Strikingly, over 70% of
these tests yield results that are below the normal range.

In addition to its well-known activity in bone metabolism, we write
to emphasize the importance of vitamin D in the normal functioning of the
immune system. Deficiency of vitamin D has been linked to a variety of
autoimmune disorders, cancers and chronic infections, notably tuberculosis
(2-4). Long-standing deficient immune function may contribute importantly
to all of these associations.

The receptor for vitamin D is expressed by virtually all cells of the
immune system. In keeping with this, vitamin D exerts several important
actions upon the innate immune system. For example, experimental models
show that vitamin D can enhance the anti-microbial activity of macrophages
and may boost their ability to kill tumour cells (4). As mentioned by
Moser et al above, vitamin D promotes the synthesis in phagocytes of
bactericidal proteins known as cathelicidins. Equally importantly, vitamin
D plays a critical role in the adaptive immune response. The heightened
sensitivity of T-cells to respond to antigen upon secondary encounter
depends critically upon vitamin D-mediated calcium signalling (5). Vitamin
D also influences the precise balance of cytokines that are produced
following T-cell activation, which may have important implications for the
type and appropriateness of inflammatory response that ensues (4).

As a clinical immunologist (JM), I commonly see patients with
recurrent or unexplained infection in whom routine immunological testing
reveals no clear-cut abnormalities. The role of vitamin D deficiency in
this clinical scenario is worthy of study. Furthermore, it would be of
interest to examine the immunological consequences of vitamin D status in
the general population and whether this impacts upon effectiveness of
immunomodulatory therapies, such as monoclonal antibodies and vaccines.

1. Iqbal SJ, Kaddam I, Wassif W, Nichol F, Walls J. (1994) Continuing
clinically severe vitamin D deficiency in Asians in the UK (Leicester).
Postgrad Med J 70: 708-14.

2. Williams B, Williams AJ, Anderson ST. (2008) Vitamin D deficiency
and insufficiency in children with tuberculosis. Pediatr Infect Dis J. 27:
941-2.

3. Nnoaham KE, Clarke A. (2008) Low serum vitamin D levels and
tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 37:
113-9.

4. Baeke F, Gysemans C, Korf H, Mathieu C. (2010) Vitamin D
insufficiency: implications for the immune system. Pediatr Nephrol. 2010
In press.

5. von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler
C. (2010) Vitamin D controls T cell antigen receptor signaling and
activation of human T cells. Nat Immunol. 11: 344-9.

Competing interests:
None declared

Competing interests: No competing interests

01 April 2010
John Maher
Senior Lecturer and Honorary Consultant Immunologist
Steve Heffernan
Department of Clinical Immunology, Barnet and Chase Farm NHS Trust, Herts, EN5 3DJ