Decreased vitamin A levels in common variable immunodeficiency: vitamin A supplementation in vivo enhances immunoglobulin production and downregulates inflammatory responses

BACKGROUND: Vitamin A has a broad range of immunological effects, and vitamin A deficiency is associated with recurrent infections. Common variable immunodeficiency (CVI) is a group of B-cell deficiency syndromes with impaired antibody production and recurrent bacterial infections as the major manifestations, but the immunological dysfunctions may also include T cells and macrophages. In the present study we examined the possible role of vitamin A deficiency in CVI. PATIENTS AND METHODS: We analysed plasma vitamin A levels in 20 CVI patients and 16 controls, and examined the relationships between vitamin A and clinical, immunological and metabolic parameters in CVI. In the six CVI patients with the lowest vitamin A levels we also studied the effect of vitamin A supplementation in vivo on several immunological functions in these patients. RESULTS: (i) The majority of CVI patients had decreased vitamin A levels compared with healthy controls, as found in both cross-sectional and longitudinal testing. (ii) Low vitamin A levels were associated with the occurrence of chronic bacterial infections and splenomegaly as well as high neopterin levels. Decreased levels of carrier protein and malabsorption were not observed. (iii) Vitamin A supplementation in patients with low vitamin A levels resulted in increased interleukin-10 (IL-10) and decreased tumour necrosis factor-alpha (TNFalpha) levels, as found in both plasma and monocyte supernatants, possibly favouring anti-inflammatory net effects. (iv) Vitamin A supplementation in vivo also enhanced anti-CD40-stimulated IgG production, serum IgA levels and phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cell (PBMC) proliferation. CONCLUSION: A considerable subgroup of CVI patients appears to be characterized by low vitamin A levels. Our findings support a possible role for vitamin A supplementation in CVI, perhaps resulting in enhanced immunoglobulin synthesis and downregulated inflammatory responses.