Advertisement

Immunogenetics of IgG4-Related AIP

  • Masao Ota
  • Takeji Umemura
  • Shigeyuki Kawa
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 401)

Abstract

Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis characterized by high serum IgG4 concentration and a variety of complicating extra-pancreatic lesions. AIP has the features of a complex disease that is caused by multifactorial genes. However, the genetic factors underlying AIP have not been elucidated conclusively. Association studies by the candidate-gene approach and genome-wide association studies (GWAS) have revealed several susceptibility genes for AIP, including HLA DRB1*04:05-DQB1*04:01, FCRL3, CTLA4, and KCNA3, albeit in small-scale analyses. Thus, GWAS of large sample sizes and multinational collaborative meta-analyses are needed to identify the precise genetic variants that are associated with AIP onset. Systems genetics approaches that integrate DNA sequencing, expression quantitative trait locus (eQTL) mapping, proteomics, and metabolomics will also be useful in clarifying the pathogenesis of AIP.

Keywords

Human Leukocyte Antigen Human Leukocyte Antigen Class Autoimmune Pancreatitis Human Leukocyte Antigen Allele Expression Quantitative Trait Locus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124(4):783–801. doi: 10.1016/j.cell.2006.02.015 CrossRefPubMedGoogle Scholar
  2. Amos W, Driscoll E, Hoffman JI (2011) Candidate genes versus genome-wide associations: which are better for detecting genetic susceptibility to infectious disease? Proc Biol Sci 278(1709):1183–1188. doi: 10.1098/rspb CrossRefPubMedGoogle Scholar
  3. Beeton C, Wulff H, Standifer NE, Azam P, Mullen KM et al (2006) Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc Natl Acad Sci USA 103(46):17414–17419. doi: 10.1073/pnas.0605136103
  4. Burn GL, Svensson L, Sanchez-Blanco C, Saini M, Cope AP (2011) Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? FEBS Lett 585(23):3689–3698. doi: 10.1016/j.febslet CrossRefPubMedGoogle Scholar
  5. Chang MC, Chang YT, Tien YW, Liang PC, Jan IS, Wei SC, Wong JM (2007) T-cell regulatory gene CTLA-4 polymorphism/haplotype association with autoimmune pancreatitis. Clin Chem 53(9):1700–1705. doi: 10.1373/clinchem.2007.085951 CrossRefPubMedGoogle Scholar
  6. Civelek M, Lusis AJ (2014) Systems genetics approaches to understand complex traits. Nat Rev Genet 15(1):34–48. doi: 10.1038/nrg3575 CrossRefPubMedGoogle Scholar
  7. Fairfax BP, Knight JC (2014) Genetics of gene expression in immunity to infection. Curr Opin Immunol 30:63–71. doi: 10.1016/j.coi.2014.07.001 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Fernando MM, Stevens CR, Walsh EC, De Jager PL, Goyette P, Plenge RM, Vyse TJ, Rioux JD (2008) Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS Genet: e1000024. doi: 10.1371/journal.pgen.1000024
  9. Freitag TL, Cham C, Sung HH, Beilhack GF, Durinovic-Belló I, Patel SD, Bronson RT, Schuppan D, Sønderstrup G (2010) Human risk allele HLA-DRB1*0405 predisposes class II transgenic Ab0 NOD mice to autoimmune pancreatitis. Gastroenterology 139(1):281–291. doi: 10.1053/j.gastro.2010.03.038 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Gough SC, Walker LS, Sansom DM (2005) CTLA4gene polymorphism and autoimmunity. Immunol Rev 204:102–115. doi: 10.1111/j.0105-2896.2005.00249.x CrossRefPubMedGoogle Scholar
  11. Gregersen PK, Behrens TW (2006) Genetics of autoimmune diseases–disorders of immune homeostasis. Nat Rev Genet 7(12):917–928. doi: 10.1038/nrg1944 CrossRefPubMedGoogle Scholar
  12. Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, Fukushima M, Nikaido T, Nakayama K, Usuda N, Kiyosawa K (2001) High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 344(10):732–738. doi: 10.1056/NEJM200103083441005 CrossRefPubMedGoogle Scholar
  13. Hamano H, Kawa S, Ochi Y, Unno H, Shiba N, Wajiki M, Nakazawa K, Shimojo H, Kiyosawa K (2002) Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet 20(359):1403–1404. doi: 10.1016/S0140-6736(02)08359-9 CrossRefGoogle Scholar
  14. Hirano K, Asaoka Y, Tada M, Isayama H, Sasahira N, Tsujino T, Kawabe T, Omata M (2009) No significant relation between relapse of autoimmune pancreatitis and substitution of aspartic acid at position 57 of DQbeta1. J Gastroenterol 44(7):799–800. doi: 10.1007/s00535-009-0080-4 CrossRefPubMedGoogle Scholar
  15. Ikari K, Momohara S, Nakamura T, Hara M, Yamanaka H, Tomatsu T, Kamatani N (2006) Supportive evidence for a genetic association of the FCRL3 promoter polymorphism with rheumatoid arthritis. Ann Rheum Dis 65(5):671–673. doi: 10.1136/ard.2005.043489 CrossRefPubMedGoogle Scholar
  16. Kamisawa T, Funata N, Hayashi Y, Tsuruta K, Okamoto A, Amemiya K, Egawa N, Nakajima H (2003) Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut 52(5):683–687. doi: 10.1136/gut.52.5.683 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Kamisawa T, Notohara K, Shimosegawa T (2010) Two clinicopathologic subtypes of autoimmune pancreatitis: LPSP and IDCP. Gastroenterology 139(1):22–25. doi: 10.1053/j.gastro.2010.05.019 CrossRefPubMedGoogle Scholar
  18. Kawa S, Ota M, Yoshizawa K, Horiuchi A, Hamano H, Ochi Y, Nakayama K, Tokutake Y, Katsuyama Y, Saito S, Hasebe O, Kiyosawa K (2002) HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population. Gastroenterology 122(5):1264–1269. doi: 10.1053/gast.2002.33022 CrossRefPubMedGoogle Scholar
  19. Kochi Y, Yamada R, Suzuki A, Harley JB, Shirasawa S, Sawada T, Bae SC, Tokuhiro S, Chang X, Sekine A, Takahashi A, Tsunoda T, Ohnishi Y, Kaufman KM, Kang CP, Kang C, Otsubo S, Yumura W, Mimori A, Koike T, Nakamura Y, Sasazuki T, Yamamoto K (2005) A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. Nat Genet 37(5):478–485. doi: 10.1038/ng1540 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Masaki Y, Dong L, Kurose N, Kitagawa K, Morikawa Y, Yamamoto M, Takahashi H, Shinomura Y, Imai K, Saeki T, Azumi A, Nakada S, Sugiyama E, Matsui S, Origuchi T, Nishiyama S, Nishimori I, Nojima T, Yamada K, Kawano M, Zen Y, Kaneko M, Miyazaki K, Tsubota K, Eguchi K, Tomoda K, Sawaki T, Kawanami T, Tanaka M, Fukushima T, Sugai S, Umehara H (2009) Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis 68(8):1310–1315. doi: 10.1136/ard.2008.089169 CrossRefPubMedGoogle Scholar
  21. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL et al (2003) The DNA sequence and analysis of human chromosome 6. Nature 425(6960):805–811. doi: 10.1038/nature02055 CrossRefPubMedGoogle Scholar
  22. Oguchi T, Ota M, Ito T, Hamano H, Arakura N, Katsuyama Y, Meguro A, Kawa S. (2015) Investigation of susceptibility genes triggering lachrymal/salivary gland lesion complications in Japanese patients with type 1 autoimmune pancreatitis. PLoS One: e0127078. doi: 10.1371/journal.pone.0127078 (eCollection 2016;11(1):e0146738. doi: 10.1371/journal.pone.0146738)
  23. Ota M, Katsuyama Y, Hamano H, Umemura T, Kimura A, Yoshizawa K, Kiyosawa K, Fukushima H, Bahram S, Inoko H, Kawa S (2007) Two critical genes (HLA-DRB1 and ABCF1) in the HLA region are associated with the susceptibility to autoimmune pancreatitis. Immunogenetics 59(1):45–52. doi: 10.1007/s00251-006-0178-2 CrossRefPubMedGoogle Scholar
  24. Ota M, Ito T, Umemura T, Katsuyama Y, Yoshizawa K, Hamano H, Kawa S (2011) Polymorphism in the KCNA3 gene is associated with susceptibility to autoimmune pancreatitis in the Japanese population. Dis Markers 31(4):223–229. doi: 10.3233/DMA-2011-0820 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Park DH, Kim MH, Oh HB, Kwon OJ, Choi YJ, Lee SS, Lee TY, Seo DW, Lee SK (2008) Substitution of aspartic acid at position 57 of the DQbeta1 affects relapse of autoimmune pancreatitis. Gastroenterology 134(2):440–446. doi: 10.1053/j.gastro.2007.11.023 CrossRefPubMedGoogle Scholar
  26. Sah RP, Chari ST, Pannala R, Sugumar A, Clain JE, Levy MJ, Pearson RK, Smyrk TC, Petersen BT, Topazian MD, Takahashi N, Farnell MB, Vege SS (2010) Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis. Gastroenterology 139(1):140–148. doi: 10.1053/j.gastro.2010.03.054
  27. Shiina T, Hosomichi K, Inoko H, Kulski JK (2009) The HLA genomic loci map: expression, interaction, diversity and disease. J Hum Genet 54(1):15–39. doi: 10.1038/jhg.2008.5 CrossRefPubMedGoogle Scholar
  28. Shimosegawa T, Chari ST, Frulloni L, Kamisawa T, Kawa S, Mino-Kenudson M, Kim MH, Klöppel G, Lerch MM, Löhr M, Notohara K, Okazaki K, Schneider A, Zhang L; International Association of Pancreatology (2011) International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas 40(3):352–358. doi: 10.1097/MPA.0b013e3182142fd2
  29. Stone JH, Khosroshahi A, Deshpande V, Chan JK, Heathcote JG et al (2012) Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum 64:3061–3067. doi: 10.1002/art.34593 CrossRefPubMedGoogle Scholar
  30. Ueda H, Howson JM, Esposito L, Heward J, Snook H, et al (2003) Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 423(6939):506–511. doi: 10.1038/nature01621
  31. Umemura T, Ota M, Hamano H, Katsuyama Y, Kiyosawa K, Kawa S (2006) Genetic association of Fc receptor-like 3 polymorphisms with autoimmune pancreatitis in Japanese patients. Gut 55(9):1367–1368. doi: 10.1136/gut.2006.095059
  32. Umemura T, Ota M, Hamano H, Katsuyama Y, Muraki T, Arakura N, Kawa S, Kiyosawa K (2008) Association of autoimmune pancreatitis with cytotoxic T-lymphocyte antigen 4 gene polymorphisms in Japanese patients. Am J Gastroenterol 103(3):588–594. doi: 10.1111/j.1572-0241 CrossRefPubMedGoogle Scholar
  33. Umemura T, Katsuyama Y, Hamano H, Kitahara K, Takayama M, Arakura N, Kawa S, Tanaka E, Ota M (2009) Association analysis of Toll-like receptor 4 polymorphisms with autoimmune pancreatitis. Hum Immunol 70(9):742–746. doi: 10.1016/j.humimm.2009.05.009 CrossRefPubMedGoogle Scholar
  34. Yamamoto M, Harada S, Ohara M, Suzuki C, Naishiro Y, Yamamoto H, Takahashi H, Imai K (2005) Clinical and pathological differences between Mikulicz’s disease and Sjögren’s syndrome. Rheumatology 44(2):227–234. doi: 10.1093/rheumatology/keh447 CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Legal MedicineShinshu University School of MedicineMatsumotoJapan
  2. 2.Department of Internal Medicine, Division of Gastroenterology and HepatologyShinshu University School of MedicineMatsumotoJapan
  3. 3.Center for Health, Safety, and Environmental ManagementShinshu UniversityMatsumotoJapan

Personalised recommendations