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The Immunological Role of Vitamin D in Primary Immunodeficiencies: A Narrative Review of the Current Literature

Zumbo E, Nuccio F, Paladin F, Murdaca G, Gangemi S

Biomedicines, 2026

2 citations

Abstract

Vitamin D is a fat-soluble hormone essential for bone mineralization. In addition to this role, vitamin D is known for its immunomodulatory effects through its binding to intracellular vitamin D receptors (VDRs), which translocate to the nucleus of immune cells, including antigen-presenting cells (APC), B lymphocytes, T lymphocytes and monocytes, thereby modulating the transcription of genes responsible for the immune response. Vitamin D deficiency is associated with an increased risk of developing infections and autoimmune diseases. The purpose of this review is to evaluate vitamin D deficiency in patients with primary immunodeficiency (CVID, XLA, DGS, APECED, SCID, WAS, HIES), to assess its clinical and therapeutic impact. Vitamin D deficiency, often asymptomatic, is associated with more severe clinical conditions in subjects with PID. It can be associated with osteoporosis, fractures, myelofibrosis and endocrine disorders such as hypocalcemia. These patients responded beneficially to calcitriol therapy, underscoring the need for long-term monitoring.

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