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Hypovitaminosis D as Predisposing Factor for Atrophic Type A Gastritis: a Case–Control Study and Review of the Literature on the Interaction of Vitamin D with the Immune System

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Abstract

1,25-Dihydroxyvitamin D displays immunoregulatory and anti-inflammatory properties, and the cells involved in innate and adaptive immune response express the vitamin D receptor and can both produce and respond to this hormone. This article aims at describing the complex immune regulatory role of vitamin D and depicting whether a correlation exists between atrophic type A gastritis and hypovitaminosis. We studied 62 autoimmune gastritis (AIG) patients and compared them to 54 lymphocytic gastritis patients, 21 Helicobacter pylori gastritis patients and 212 healthy subjects. We also statistically analyzed vitamin D concentration in 36,384 outpatients referred to our clinical laboratories. 25-Hydroxyvitamin D levels, the measurable metabolite used to determine vitamin D status in plasma, were measured by a chemiluminescent method. Average level of 25-OHD in AIG subjects was 9.8 ± 5.6 ng/mL (95% confidence interval (CI) 8.4–11.2), 11.1 ± 8.4 (CI 7.5–14.7) in H. pylori gastritis patients, 22.2 ± 13.5 (CI 18.6–25.8) in nonspecific lymphocytic gastritis patients, 21.3 ± 12.2 (CI 19.7–22.9) in healthy subjects, and 21.8 ± 13.1 (CI 21.7–21.9) in the 36,384 outpatients. Vitamin D levels in AIG patients were significantly lower than in patients with nonspecific gastritis or in the general population, supporting the hypothesis that hypovitaminosis D might be a risk factor for the development of autoimmune diseases. The low vitamin D concentration in H. pylori gastritis patients might act as predisposing factor for a more severe Th1-type aggression to the stomach epithelium.

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References

  1. Norman AW (2008) From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 88:491S–499S

    Article  PubMed  CAS  Google Scholar 

  2. Zhang R, Naughton DP (2010) Vitamin D in health and disease: current perspectives. Nutr J 9:65

    Article  PubMed  CAS  Google Scholar 

  3. Cappelletti P, Tozzoli R (2010) Laboratory and hypercalcemia. In: Lumachi F, Basso SMM (eds) Hypercalcemia pathophysiology and treatment. Bentham Science, Sharjah, pp 45–61

    Chapter  Google Scholar 

  4. Rojas-Rivera J, De La Piedra C, Ramos A et al (2010) The expanding spectrum of biological actions of vitamin D. Nephrol Dial Transplant 25:2850–2865

    Article  PubMed  CAS  Google Scholar 

  5. Hewison M, Zehnder D, Chakraverty R et al (2004) Vitamin D and barrier function: a novel role for extra-renal 1a-hydroxylase. Mol Cell Endocrinol 215:31–38

    Article  PubMed  CAS  Google Scholar 

  6. Bises G, Kallay E, Weiland T et al (2004) 25-Hydroxyvitamin D3-1alpha-hydroxylase expression in normal and malignant human colon. J Histochem Cytochem 52:985–989

    Article  PubMed  CAS  Google Scholar 

  7. Adorini L, Penna G, Giarratana N et al (2004) Dendritic cells as key targets for immunomodulation by vitamin D receptor ligands. J Steroid Biochem Mol Biol 89–90:437–441

    Article  PubMed  Google Scholar 

  8. Zehnder D, Bland R, Chana RS et al (2002) Synthesis of 1, 25-dihydroxyvitamin D3 by human endothelial cells is regulated by inflammatory cytokines: a novel autocrine determinant of vascular cell adhesion. J Am Soc Nephrol 13:621–629

    PubMed  CAS  Google Scholar 

  9. Eyles DW, Smith S, Kinobe R et al (2005) Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 29:21–30

    Article  PubMed  CAS  Google Scholar 

  10. Segersten U, Holm PK, Bjorklund P et al (2005) 25-Hydroxyvitamin D3 1alpha-hydroxylase expression in breast cancer and use of non-1-hydroxylated vitamin D analogue. Breast Cancer Res 7:980–986

    Article  Google Scholar 

  11. Townsend K, Evans KN, Campbell MJ et al (2005) Biological actions of extra-renal 25-hydroxyvitamin D-1alpha-hydroxylase and implications for chemoprevention and treatment. J Steroid Biochem Mol Biol 97:103–119

    Article  PubMed  CAS  Google Scholar 

  12. Segersten U, Correa P, Hewison M et al (2002) 25-Hydroxyvitamin D(3)-1alpha-hydroxylase expression in normal and pathological parathyroid glands. J Clin Endocrinol Metab 87:2967–2972

    Article  PubMed  CAS  Google Scholar 

  13. Evans KN, Bulmer JN, Kilby MD et al (2004) Vitamin D and placental–decidual function. J Soc Gynecol Investig 11:263–271

    Article  PubMed  CAS  Google Scholar 

  14. Ma JF, Nonn L, Campbell MJ et al (2004) Mechanisms of decreased vitamin D 1alpha-hydroxylase activity in prostate cancer cells. Mol Cell Endocrinol 221:67–74

    Article  PubMed  CAS  Google Scholar 

  15. Bikle DD, Chang S, Crumrine D et al (2004) 25 Hydroxyvitamin D 1 alpha-hydroxylase is required for optimal epidermal differentiation and permeability barrier homeostasis. J Invest Dermatol 122:984–992

    Article  PubMed  CAS  Google Scholar 

  16. Griffin MD, Xing N, Kumar R (2003) Vitamin D and its analogs as regulators of immune activation and antigen presentation. Annu Rev Nutr 23:117–145

    Article  PubMed  CAS  Google Scholar 

  17. Norman AW, Mizwicki MT, Okamura WH (2003) Ligand structure–function relationships in the vitamin D endocrine system from the perspective of drug development (including cancer treatment). Recent Results Cancer Res 164:55–82

    PubMed  CAS  Google Scholar 

  18. Holick MF (2006) Resurrection of vitamin D deficiency and rickets. J Clin Invest 116:2062–2072

    Article  PubMed  CAS  Google Scholar 

  19. DeLuca HF (2004) Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 80:1689–1696

    Google Scholar 

  20. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

    Article  PubMed  CAS  Google Scholar 

  21. Cooke NE, Haddad JG (1989) Vitamin D binding protein (Gc-globulin). Endocr Rev 10:294–307

    Article  PubMed  CAS  Google Scholar 

  22. Dusso AS, Negrea L, Gunawardhana S et al (1991) On the mechanisms for the selective action of vitamin D analogs. Endocrinology 128:1687–1692

    Article  PubMed  CAS  Google Scholar 

  23. Takemoto F, Shinki T, Yokoyama K et al (2003) Gene expression of vitamin D hydroxylase and megalin in the remnant kidney of nephrectomized rats. Kidney Int 64:414–420

    Article  PubMed  CAS  Google Scholar 

  24. Yamane T, Takeuchi K, Yamamoto Y et al (2002) Legumain from bovine kidney: its purification, molecular cloning, immunohistochemical localization and degradation of annexin II and vitamin D-binding protein. Biochim Biophys Acta 1596:108–120

    Article  PubMed  CAS  Google Scholar 

  25. Adams JS, Chen H, Chun RF et al (2003) Novel regulators of vitamin D action and metabolism: lessons learned at the Los Angeles zoo. J Cell Biochem 88:308–314

    Article  PubMed  CAS  Google Scholar 

  26. Nykjaer A, Dragun D, Walther D et al (1999) An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell 96:507–515

    Article  PubMed  CAS  Google Scholar 

  27. Liu W, Yu WR, Carling T et al (1998) Regulation of gp330/megalin expression by vitamins A and D. Eur J Clin Investig 28:100–107

    Article  CAS  Google Scholar 

  28. Brandi L (2008) 1alpha(OH)D3 One-alpha-hydroxy-cholecalciferol—an active vitamin D analog. Clinical studies on prophylaxis and treatment of secondary hyperparathyroidism in uremic patients on chronic dialysis. Dan Med Bull 55:186–210

    PubMed  CAS  Google Scholar 

  29. Brenza HL, Kimmel-Jehan C, Jehan F et al (1998) Parathyroid hormone activation of the 25-hydroxyvitamin D3-1alpha-hydroxylase gene promoter. Proc Natl Acad Sci USA 95:1387–1391

    Article  PubMed  CAS  Google Scholar 

  30. Tsujikawa H, Kurotaki Y, Fujimori T et al (2003) Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol Endocrinol 17:2393–2403

    Article  PubMed  CAS  Google Scholar 

  31. Dong X, Lutz W, Schroeder TM et al (2005) Regulation of relB in dendritic cells by means of modulated association of vitamin D receptor and histone deacetylase 3 with the promoter. Proc Natl Acad Sci USA 102:16007–16012

    Article  PubMed  CAS  Google Scholar 

  32. Adorini L, Penna G (2008) Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol 4:404–412

    Article  PubMed  CAS  Google Scholar 

  33. Norman AW, Mizwicki MT, Norman DPG (2004) Steroid hormone rapid actions, membrane receptors and a conformational ensemble model. Nat Rev Drug Discov 3:27–41

    Article  PubMed  CAS  Google Scholar 

  34. Pinette KV, Yee YK, Amegadzie BY et al (2003) Vitamin D receptor as a drug discovery target. Min Rev Med Chem 3:193–204

    Article  CAS  Google Scholar 

  35. Brown AJ, Dusso A, Slatopolsky E (1999) Vitamin D. Am J Physiol Renal Physiol 277:F157–F175

    CAS  Google Scholar 

  36. Sutton ALM, MacDonald PN (2003) Vitamin D: more than a “bone-a-fide” hormone. Mol Endocrinol 17:777–791

    Article  PubMed  CAS  Google Scholar 

  37. Strugnell SA, Deluca HF (1997) The vitamin D receptor—structure and transcriptional activation. Proc Soc Exp Biol Med 215:223–228

    PubMed  CAS  Google Scholar 

  38. Kliewer SA, Umesono K, Mangelsdorf DJ et al (1992) Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature 355:446–449

    Article  PubMed  CAS  Google Scholar 

  39. Cheskis B, Freedman LP (1994) Ligand modulates the conversion of DNA-bound vitamin D3 receptor (VDR) homodimers into VDR-retinoid X receptor heterodimers. Mol Cell Biol 14:3329–3338

    PubMed  CAS  Google Scholar 

  40. Dusso AS, Brown AJ (2009) Vitamin D: molecular biology and gene regulation. In: Singh AJ, Williams GH (eds) Textbook of nephro-endocrinology. Elsevier, San Diego, pp 69–93

    Chapter  Google Scholar 

  41. Nagpal S, Na S, Rathnachalam R (2005) Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 26:662–687

    Article  PubMed  CAS  Google Scholar 

  42. Oñate SA, Tsai SY, Tsai MJ et al (1995) Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 270:1354–1357

    Article  PubMed  Google Scholar 

  43. Chen HW, Lin RJ, Schiltz RL et al (1997) Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell 90:569–580

    Article  PubMed  CAS  Google Scholar 

  44. Rachez C, Suldan Z, Ward J et al (1998) A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system. Genes Dev 12:1787–1800

    Article  PubMed  CAS  Google Scholar 

  45. Chiba N, Suldan Z, Freedman LP et al (2000) Binding of liganded vitamin D receptor to the vitamin D receptor interacting protein coactivator complex induces interaction with RNA polymerase II holoenzyme. J Biol Chem 275:10719–10722

    Article  PubMed  CAS  Google Scholar 

  46. Carvallo L, Henríquez B, Paredes R et al (2008) 1alpha, 25-Dihydroxy vitamin D3-enhanced expression of the osteocalcin gene involves increased promoter occupancy of basal transcription regulators and gradual recruitment of the 1alpha, 25-dihydroxy vitamin D3 receptor-SRC-1 coactivator complex. J Cell Physiol 214:740–749

    Article  PubMed  CAS  Google Scholar 

  47. Baudino TA, Kraichely DM, Jefcoat SC Jr et al (1998) Isolation and characterization of a novel coactivator protein, NCoA-62, involved in vitamin D-mediated transcription. J Biol Chem 273:16434–16441

    Article  PubMed  CAS  Google Scholar 

  48. Zhang C, Dowd DR, Staal A et al (2003) Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing. J Biol Chem 278:35325–35336

    Article  PubMed  CAS  Google Scholar 

  49. Dunlop TW, Väisänen S, Frank C et al (2004) The genes of the coactivator TIF2 and the corepressor SMRT are primary 1alpha, 25(OH)2D3 targets. J Steroid Biochem Mol Biol 89–90:257–260

    Article  PubMed  Google Scholar 

  50. Adorini L, Penna G (2009) Dendritic cell tolerogenicity: a key mechanism in immunomodulation by vitamin D receptor agonists. Hum Immunol 70:345–352

    Article  PubMed  CAS  Google Scholar 

  51. Cutolo M (2009) Vitamin D and autoimmune rheumatic diseases. Rheumatology 48:210–212

    Article  PubMed  CAS  Google Scholar 

  52. van Etten E, Mathieu C (2005) Immunoregulation by 1, 25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol 97:93–101

    Article  PubMed  Google Scholar 

  53. Liu PT, Stenger S, Li H et al (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311:1770–1773

    Article  PubMed  CAS  Google Scholar 

  54. Wang TT, Nestel FP, Bourdeau V et al (2004) Cutting edge: 1, 25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173:2909–2912

    PubMed  CAS  Google Scholar 

  55. Schauber J, Dorschner RA, Coda AB et al (2007) Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 117:803–811

    Article  PubMed  CAS  Google Scholar 

  56. Sigmundsdottir H, Pan J, Debes GF et al (2007) DCs metabolize sunlight-induced vitamin D3 to ‘program’ T cell attraction to the epidermal chemokine CCL27. Nat Immunol 8:285–293

    Article  PubMed  CAS  Google Scholar 

  57. Chen S, Sims GP, Chen XX et al (2007) Modulatory effects of 1, 25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 179:1634–1647

    PubMed  CAS  Google Scholar 

  58. Mattner F, Smiroldo S, Galbiati F et al (2000) Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1, 25-dihydroxyvitamin D(3). Eur J Immunol 30:498–508

    Article  PubMed  CAS  Google Scholar 

  59. Cippitelli M, Santoni A (1998) Vitamin D3: a transcriptional modulator of the interferon-gamma gene. Eur J Immunol 28:3017–3030

    Article  PubMed  CAS  Google Scholar 

  60. Penna G, Amuchastegui S, Cossetti C et al (2006) Treatment of experimental autoimmune prostatitis in nonobese diabetic mice by the vitamin D receptor agonist elocalcitol. J Immunol 177:8504–8511

    PubMed  CAS  Google Scholar 

  61. Penna G, Amuchastegui S, Giarratana N et al (2007) 1, 25-Dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells. J Immunol 178:145–153

    PubMed  CAS  Google Scholar 

  62. Adorini L, Giarratana N, Penna G (2004) Pharmacological induction of tolerogenic dendritic cells and regulatory T cells. Semin Immunol 16:127–134

    Article  PubMed  CAS  Google Scholar 

  63. Penna G, Adorini L (2000) 1 alpha, 25-Dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 164:2405–2411

    PubMed  CAS  Google Scholar 

  64. Penna G, Roncari A, Amuchastegui S et al (2005) Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4 + Foxp3+ regulatory T cells by 1, 25-dihydroxyvitamin D3. Blood 106:3490–3497

    Article  PubMed  CAS  Google Scholar 

  65. Hewison M, Freeman L, Hughes SV et al (2003) Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells. J Immunol 170:5382–5390

    PubMed  CAS  Google Scholar 

  66. Adorini L (2005) Intervention in autoimmunity: the potential of vitamin D receptor agonists. Cell Immunol 233:115–124

    Article  PubMed  CAS  Google Scholar 

  67. Griffin MD, Dong X, Kumar R (2007) Vitamin D receptor-mediated suppression of RelB in antigen presenting cells: a paradigm for ligand-augmented negative transcriptional regulation. Arch Biochem Biophys 460:218–226

    Article  PubMed  CAS  Google Scholar 

  68. Liu YJ (2005) IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol 23:275–306

    Article  PubMed  CAS  Google Scholar 

  69. Lemire JM, Archer DC, Beck L et al (1995) Immunosuppressive actions of 1, 25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. J Nutr 125:1704S–1708S

    PubMed  CAS  Google Scholar 

  70. D’Ambrosio D, Cippitelli M, Cocciolo MG et al (1998) Inhibition of IL-12 production by 1, 25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. J Clin Invest 101:252–262

    Article  PubMed  Google Scholar 

  71. Boonstra A, Barrat FJ, Crain C et al (2001) 1alpha, 25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 167:4974–4980

    PubMed  CAS  Google Scholar 

  72. Mahon BD, Wittke A, Weaver V et al (2003) The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells. J Cell Biochem 89:922–932

    Article  PubMed  CAS  Google Scholar 

  73. Steinman L (2007) A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med 13:139–145

    Article  PubMed  CAS  Google Scholar 

  74. Gregori S, Giarratana N, Smiroldo S et al (2002) A 1alpha, 25-dihydroxyvitamin D(3) analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice. Diabetes 51:1367–1374

    Article  PubMed  CAS  Google Scholar 

  75. Gregori S, Casorati M, Amuchastegui S et al (2001) Regulatory T cells induced by 1 alpha, 25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol 167:1945–1953

    PubMed  CAS  Google Scholar 

  76. Curiel TJ, Coukos G, Zou L et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949

    Article  PubMed  CAS  Google Scholar 

  77. Adams JS, Hewison M (2010) Update in vitamin D. J Clin Endocrinol Metab 95:471–478

    Article  PubMed  Google Scholar 

  78. Antico A (2008) Autoimmune gastritis. It J Lab Med 4:125–133

    CAS  Google Scholar 

  79. De Block CE, De Leeuw IH, Van Gaal LF (2008) Autoimmune gastritis in type 1 diabetes: a clinically oriented review. J Clin Endocrinol Metab 93:363–371

    Article  PubMed  Google Scholar 

  80. Holick MF (2006) High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 81:353–373

    Article  PubMed  CAS  Google Scholar 

  81. Kairisto V, Poola A (1995) Software for illustrative presentation of basic clinical characteristics of laboratory tests—GraphROC for Windows. Scand J Clin Lab Invest 222:43–60

    Article  CAS  Google Scholar 

  82. Holick MF, Chen TC (2008) Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 87:1080–1086

    Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Pathology, Cittadella General Hospital, Cittadella, Italy

    Antonio Antico

  2. Laboratory of Clinical Chemistry and Microbiology, Beata Vergine delle Grazie Hospital, Latisana, Italy

    Renato Tozzoli

  3. Laboratory of Clinical Chemistry and Hematology, Vicenza General Hospital, Vicenza, Italy

    Davide Giavarina

  4. Clinical Immunology and Allergology, Udine University Hospital, Udine, Italy

    Elio Tonutti

  5. Laboratory of Clinical Pathology, S. Antonio Hospital, via Morgagni, 18, 33028, Tolmezzo, Udine, Italy

    Nicola Bizzaro

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  1. Antonio Antico
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Antico, A., Tozzoli, R., Giavarina, D. et al. Hypovitaminosis D as Predisposing Factor for Atrophic Type A Gastritis: a Case–Control Study and Review of the Literature on the Interaction of Vitamin D with the Immune System. Clinic Rev Allerg Immunol 42, 355–364 (2012). https://doi.org/10.1007/s12016-011-8255-1

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