Top

Published in:

Open Access 01-04-2012 | Research article

Serum BAFF and APRIL levels in patients with IgG4-related disease and their clinical significance

Published in: Arthritis Research & Therapy | Issue 2/2012

Abstract

Introduction

B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play a crucial role in B cell development, survival, and antibody production. Here we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with an immunoglobulin (Ig) G4-related disease (IgG4-RD).

Methods

We measured serum levels of BAFF and APRIL in patients with IgG4-RD, primary Sjögren's syndrome (pSS), and healthy individuals. Serum BAFF and APRIL levels in IgG4-RD were assessed for correlations with serological parameters, including Ig, particularly IgG4, and the number of affected organs. Serum BAFF and APRIL levels in IgG4-RD were monitored during glucocorticoid (GC) therapy.

Results

Serum BAFF and APRIL levels in patients with IgG4-RD were significantly higher (P < 0.01) than in healthy individuals. The BAFF levels of patients with IgG4-RD were comparable to those of patients with pSS. Although clinical parameters, such as serum IgG4 and the number of affected organs, were not correlated with the levels of BAFF, serum APRIL levels were inversely correlated with serum IgG4 levels (r = -0.626, P < 0.05). While serum BAFF levels decreased following GC therapy, serum APRIL levels increased during follow-up.

Conclusion

These results indicate that BAFF and APRIL might be useful markers for predicting disease activity in IgG4-RD. Further studies are needed to elucidate the role of BAFF and APRIL in the pathogenesis of IgG4-RD.

Available only for authorised users

Masaki Y, Kurose N, Umehara H: IgG4-related disease: a novel lymphoproliferative disorder discovered and established in Japan in the 21st century. J Clin Exp Hematop. 2011, 51: 13-20. 10.3960/jslrt.51.13.CrossRefPubMed

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: Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis. 2009, 68: 1310-1315. 10.1136/ard.2008.089169.CrossRefPubMed

Okazaki K, Uchida K, Miyoshi H, Ikeura T, Takaoka M, Nishio A: Recent concepts of autoimmune pancreatitis and IgG4-related disease. Clin Rev Allergy Immunol. 2011, 41: 126-138. 10.1007/s12016-010-8214-2.CrossRefPubMed

Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, Matsui S, Sumida T, Mimori T, Tanaka Y, Tsubota K, Yoshino T, Kawa S, Suzuki R, Takegami T, Tomosugi N, Kurose N, Ishigaki Y, Azumi A, Kojima M, Nakamura S, Inoue D: A novel clinical entity, IgG4-related disease (IgG4-RD): general concept and details. Mod Rheumatol. 2011, 22: 1-14.PubMedCentralCrossRefPubMed

Deshpande V, Chicano S, Finkelberg D, Selig MK, Mino-Kenudson M, Brugge WR, Colvin RB, Lauwers GY: Autoimmune pancreatitis: a systemic immune complex mediated disease. Am J Surg Pathol. 2006, 30: 1537-1545. 10.1097/01.pas.0000213331.09864.2c.CrossRefPubMed

Otsuki M, Chung JB, Okazaki K, Kim MH, Kamisawa T, Kawa S, Park SW, Shimosegawa T, Lee K, Ito T, Nishimori I, Notohara K, Naruse S, Ko SB, Kihara Y: Asian diagnostic criteria for autoimmune pancreatitis: consensus of the Japan-Korea Symposium on Autoimmune Pancreatitis. J Gastroenterol. 2008, 43: 403-408. 10.1007/s00535-008-2205-6.CrossRefPubMed

Chari ST, Smyrk TC, Levy MJ, Topazian MD, Takahashi N, Zhang L, Clain JE, Pearson RK, Petersen BT, Vege SS, Farnell MB: Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol. 2006, 4: 1010-1016; quiz 1934. 10.1016/j.cgh.2006.05.017.CrossRefPubMed

Takuma K, Kamisawa T, Igarashi Y: Autoimmune pancreatitis and IgG4-related sclerosing cholangitis. Curr Opin Rheum. 2011, 23: 80-87. 10.1097/BOR.0b013e3283412f60.CrossRef

Kitagawa S, Zen Y, Harada K, Sasaki M, Sato Y, Minato H, Watanabe K, Kurumaya H, Katayanagi K, Masuda S, Niwa H, Tsuneyama K, Saito K, Haratake J, Takagawa K, Nakanuma Y: Abundant IgG4-positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Kuttner's tumor). Am J Surg Pathol. 2005, 29: 783-791. 10.1097/01.pas.0000164031.59940.fc.CrossRefPubMed

10.

Dahlgren M, Khosroshahi A, Nielsen GP, Deshpande V, Stone JH: Riedel's thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum. Arthritis Care Res. 2010, 62: 1312-1318. 10.1002/acr.20215.CrossRef

11.

Stone JH, Khosroshahi A, Hilgenberg A, Spooner A, Isselbacher EM, Stone JR: IgG4-related systemic disease and lymphoplasmacytic aortitis. Arthritis Rheum. 2009, 60: 3139-3145. 10.1002/art.24798.CrossRefPubMed

12.

Saeki T, Nishi S, Imai N, Ito T, Yamazaki H, Kawano M, Yamamoto M, Takahashi H, Matsui S, Nakada S, Origuchi T, Hirabayashi A, Homma N, Tsubata Y, Takata T, Wada Y, Saito A, Fukase S, Ishioka K, Miyazaki K, Masaki Y, Umehara H, Sugai S, Narita I: Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int. 2010, 78: 1016-1023. 10.1038/ki.2010.271.CrossRefPubMed

13.

Stone JR: Aortitis, periaortitis, and retroperitoneal fibrosis, as manifestations of IgG4-related systemic disease. Curr Opin Rheumatol. 2011, 23: 88-94. 10.1097/BOR.0b013e3283412f7c.CrossRefPubMed

14.

Hamano H, Kawa S, Ochi Y, Unno H, Shiba N, Wajiki M, Nakazawa K, Shimojo H, Kiyosawa K: Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet. 2002, 359: 1403-1404. 10.1016/S0140-6736(02)08359-9.CrossRefPubMed

15.

Okazaki K, Uchida K, Ohana M, Nakase H, Uose S, Inai M, Matsushima Y, Katamura K, Ohmori K, Chiba T: Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response. Gastroenterology. 2000, 118: 573-581. 10.1016/S0016-5085(00)70264-2.CrossRefPubMed

16.

Nishi H, Tojo A, Onozato ML, Jimbo R, Nangaku M, Uozaki H, Hirano K, Isayama H, Omata M, Kaname S, Fujita T: Anti-carbonic anhydrase II antibody in autoimmune pancreatitis and tubulointerstitial nephritis. Nephrol Dial Transplant. 2007, 22: 1273-1275. 10.1093/ndt/gfl672.CrossRefPubMed

17.

Endo T, Takizawa S, Tanaka S, Takahashi M, Fujii H, Kamisawa T, Kobayashi T: Amylase alpha-2A autoantibodies: novel marker of autoimmune pancreatitis and fulminant type 1 diabetes. Diabetes. 2009, 58: 732-737.PubMedCentralCrossRefPubMed

18.

Asada M, Nishio A, Uchida K, Kido M, Ueno S, Uza N, Kiriya K, Inoue S, Kitamura H, Ohashi S, Tamaki H, Fukui T, Matsuura M, Kawasaki K, Nishi T, Watanabe N, Nakase H, Chiba T, Okazaki K: Identification of a novel autoantibody against pancreatic secretory trypsin inhibitor in patients with autoimmune pancreatitis. Pancreas. 2006, 33: 20-26. 10.1097/01.mpa.0000226881.48204.fd.CrossRefPubMed

19.

Frulloni L, Lunardi C, Simone R, Dolcino M, Scattolini C, Falconi M, Benini L, Vantini I, Corrocher R, Puccetti A: Identification of a novel antibody associated with autoimmune pancreatitis. N Eng J Med. 2009, 361: 2135-2142. 10.1056/NEJMoa0903068.CrossRef

20.

Zen Y, Fujii T, Harada K, Kawano M, Yamada K, Takahira M, Nakanuma Y: Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology. 2007, 45: 1538-1546. 10.1002/hep.21697.CrossRefPubMed

21.

Zen Y, Nakanuma Y: Pathogenesis of IgG4-related disease. Curr Opin Rheumatol. 2011, 23: 114-118. 10.1097/BOR.0b013e3283412f4a.CrossRefPubMed

22.

Mackay F, Schneider P, Rennert P, Browning J: BAFF AND APRIL: a tutorial on B cell survival. Ann Rev Immunol. 2003, 21: 231-264. 10.1146/annurev.immunol.21.120601.141152.CrossRef

23.

Tangye SG, Bryant VL, Cuss AK, Good KL: BAFF, APRIL and human B cell disorders. Semin Immunol. 2006, 18: 305-317. 10.1016/j.smim.2006.04.004.CrossRefPubMed

24.

Lopez-Fraga M, Fernandez R, Albar JP, Hahne M: Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase. EMBO Rep. 2001, 2: 945-951. 10.1093/embo-reports/kve198.PubMedCentralCrossRefPubMed

25.

Liu Z, Davidson A: BAFF and selection of autoreactive B cells. Trends Immunol. 2011, 32: 388-394. 10.1016/j.it.2011.06.004.PubMedCentralCrossRefPubMed

26.

Mackay F, Tangye SG: The role of the BAFF/APRIL system in B cell homeostasis and lymphoid cancers. Curr Opin Pharmacol. 2004, 4: 347-354. 10.1016/j.coph.2004.02.009.CrossRefPubMed

27.

Mackay F, Schneider P: Cracking the BAFF code. Nat Rev Immunol. 2009, 9: 491-502. 10.1038/nri2572.CrossRefPubMed

28.

Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, Tschopp J, Browning JL: Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999, 190: 1697-1710. 10.1084/jem.190.11.1697.PubMedCentralCrossRefPubMed

29.

Bosello S, Youinou P, Daridon C, Tolusso B, Bendaoud B, Pietrapertosa D, Morelli A, Ferraccioli G: Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis. J Rheumatol. 2008, 35: 1256-1264.PubMed

30.

Stohl W, Metyas S, Tan SM, Cheema GS, Oamar B, Xu D, Roschke V, Wu Y, Baker KP, Hilbert DM: B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus: longitudinal observations. Arthritis Rheum. 2003, 48: 3475-3486. 10.1002/art.11354.CrossRefPubMed

31.

Mariette X, Roux S, Zhang J, Bengoufa D, Lavie F, Zhou T, Kimberly R: The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjogren's syndrome. Ann Rheum Dis. 2003, 62: 168-171. 10.1136/ard.62.2.168.PubMedCentralCrossRefPubMed

32.

Jonsson MV, Szodoray P, Jellestad S, Jonsson R, Skarstein K: Association between circulating levels of the novel TNF family members APRIL and BAFF and lymphoid organization in primary Sjogren's syndrome. J Clin Immunol. 2005, 25: 189-201. 10.1007/s10875-005-4091-5.CrossRefPubMed

33.

Krystufkova O, Vallerskog T, Helmers SB, Mann H, Putova I, Belacek J, Malmstrom V, Trollmo C, Vencovsky J, Lundberg IE: Increased serum levels of B cell-activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. Ann Rheum Dis. 2009, 68: 836-843. 10.1136/ard.2008.091405.CrossRefPubMed

34.

Matsushita T, Hasegawa M, Yanaba K, Kodera M, Takehara K, Sato S: Elevated serum BAFF levels in patients with systemic sclerosis: enhanced BAFF signaling in systemic sclerosis B lymphocytes. Arthritis Rheum. 2006, 54: 192-201. 10.1002/art.21526.CrossRefPubMed

35.

Kang JS, Yoon YD, Ahn JH, Kim SC, Kim KH, Kim HM, Moon EY: B cell-activating factor is a novel diagnosis parameter for asthma. Int Arch Allergy Immunol. 2006, 141: 181-188. 10.1159/000094897.CrossRefPubMed

36.

Jee HM, Kim KW, Hong JY, Sohn MH, Kim KE: Increased serum B cell-activating factor level in children with atopic dermatitis. Clin Exp Dermatol. 2010, 35: 593-598.CrossRefPubMed

37.

Stein JV, Lopez-Fraga M, Elustondo FA, Carvalho-Pinto CE, Rodriguez D, Gomez-Caro R, De Jong J, Martinez AC, Medema JP, Hahne M: APRIL modulates B and T cell immunity. J Clin Invest. 2002, 109: 1587-1598.PubMedCentralCrossRefPubMed

38.

Varfolomeev E, Kischkel F, Martin F, Seshasayee D, Wang H, Lawrence D, Olsson C, Tom L, Erickson S, French D, Schow P, Grewal IS, Ashkenazi A: APRIL-deficient mice have normal immune system development. Mol Cell Biol. 2004, 24: 997-1006. 10.1128/MCB.24.3.997-1006.2004.PubMedCentralCrossRefPubMed

39.

Castigli E, Scott S, Dedeoglu F, Bryce P, Jabara H, Bhan AK, Mizoguchi E, Geha RS: Impaired IgA class switching in APRIL-deficient mice. Proc Natl Acad Sci USA. 2004, 101: 3903-3908. 10.1073/pnas.0307348101.PubMedCentralCrossRefPubMed

40.

Koyama T, Tsukamoto H, Miyagi Y, Himeji D, Otsuka J, Miyagawa H, Harada M, Horiuchi T: Raised serum APRIL levels in patients with systemic lupus erythematosus. Ann Rheum Dis. 2005, 64: 1065-1067. 10.1136/ard.2004.022491.PubMedCentralCrossRefPubMed

41.

Thangarajh M, Masterman T, Rot U, Duvefelt K, Brynedal B, Karrenbauer VD, Hillert J: Increased levels of APRIL (a proliferation-inducing ligand) mRNA in multiple sclerosis. J Neuroimmunol. 2005, 167: 210-214. 10.1016/j.jneuroim.2005.06.024.CrossRefPubMed

42.

Szodoray P, Jonsson R: The BAFF/APRIL system in systemic autoimmune diseases with a special emphasis on Sjogren's syndrome. Scand J Immunol. 2005, 62: 421-428. 10.1111/j.1365-3083.2005.01688.x.CrossRefPubMed

43.

Yamada K, Kawano M, Inoue R, Hamano R, Kakuchi Y, Fujii H, Matsumura M, Zen Y, Takahira M, Yachie A, Yamagishi M: Clonal relationship between infiltrating immunoglobulin G4 (IgG4)-positive plasma cells in lacrimal glands and circulating IgG4-positive lymphocytes in Mikulicz's disease. Clin Exp Immunol. 2008, 152: 432-439. 10.1111/j.1365-2249.2008.03651.x.PubMedCentralCrossRefPubMed

44.

Yamada T, Zhang K, Yamada A, Zhu D, Saxon A: B lymphocyte stimulator activates p38 mitogen-activated protein kinase in human Ig class switch recombination. Am J Respir Cell Mol Biol. 2005, 32: 388-394. 10.1165/rcmb.2004-0317OC.CrossRefPubMed

45.

Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, Casali P, Cerutti A: DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol. 2002, 3: 822-829.PubMedCentralCrossRefPubMed

46.

Yamanishi H, Kumagi T, Yokota T, Azemoto N, Koizumi M, Kobayashi Y, Abe M, Murakami H, Hiasa Y, Matsuura B, Kawamoto H, Yamamoto K, Onji M: Clinical significance of B cell-activating factor in autoimmune pancreatitis. Pancreas. 2011, 40: 840-845. 10.1097/MPA.0b013e3182143b10.CrossRefPubMed

47.

Stohl W, Metyas S, Tan SM, Cheema GS, Oamar B, Roschke V, Wu Y, Baker KP, Hilbert DM: Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis. 2004, 63: 1096-1103. 10.1136/ard.2003.018663.PubMedCentralCrossRefPubMed

Title: Serum BAFF and APRIL levels in patients with IgG4-related disease and their clinical significance
Publication date: 01-04-2012
Published in: Arthritis Research & Therapy / Issue 2/2012
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/ar3810

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Serum BAFF and APRIL levels in patients with IgG4-related disease and their clinical significance

Abstract

Introduction

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2012

The interferon type I signature towards prediction of non-response to rituximab in rheumatoid arthritis patients

Interleukin-6 regulates anti-arthritic effect of methotrexate via reduction of SLC19A1 expression in a mouse arthritis model

Autoantibodies to transcription intermediary factor (TIF)1β associated with dermatomyositis

Thrombin induces heme oxygenase-1 expression in human synovial fibroblasts through protease-activated receptor signaling pathways

MRI and X-ray in axial spondyloarthritis: the relationship between inflammatory and structural changes

A multicenter study confirms CD226gene association with systemic sclerosis-related pulmonary fibrosis

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page