title: Decreased vitamin A levels in common variable immunodeficiency: vitamin A supplementation in vivo enhances immunoglobulin production and downregulates inflammatory responses.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Oslo, Oslo; University of Bergen, Bergen, Norway. pal.aukrust@klinmed.uio.no
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.forename: F
authors.initials: F
authors.lastname: Müller
authors.forename: T
authors.initials: T
authors.lastname: Ueland
authors.forename: A M
authors.initials: AM
authors.lastname: Svardal
authors.forename: R K
authors.initials: RK
authors.lastname: Berge
authors.forename: S S
authors.initials: SS
authors.lastname: Frøland
mesh_terms: D000328:Adult; D000368:Aged; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000150:complications* / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D019587:Dietary Supplements; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D012177:Retinol-Binding Proteins / Q000378:metabolism; D054839:Retinol-Binding Proteins, Plasma; D013601:T-Lymphocytes / Q000276:immunology; D014801:Vitamin A / Q000097:blood / Q000494:pharmacology*; D014802:Vitamin A Deficiency / Q000150:complications* / Q000276:immunology*
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D012177:Retinol-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A