Abstract
High serum IgG4 concentrations are a striking feature of many patients with IgG4-related disease (IgG4-RD). Blood levels of IgG4 often reach ten, twenty, and even thirty or more times higher than the upper limit of normal. Under the proper clinical circumstances, the finding of an elevated serum IgG4 concentration serves as a useful biomarker for the diagnosis of this condition. This serum IgG4 elevation quickly called attention to the possibility of therapies targeting cells of the B lymphocyte lineage. In addition, a greater understanding of the cellular mechanisms that underpin IgG4-RD has identified peripheral blood plasmablasts as a promising biomarker for this disease. The roles of plasmablasts and B cells in IgG4-RD are discussed in this chapter.
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References
Allen CDC, Okada T, Cyster JG (2007) Germinal-center organization and cellular dynamics. Immunity 27(2):190–202
Carruthers MN, Topazian MD, Khosroshahi A, Witzig TE, Wallace ZS, Hart PA, Deshpande V, Smyrk TC, Chari S, Stone JH (2015) Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis 74:1171–1177
Chavele K-M, Merry E, Ehrenstein MR (2015) Cutting edge: circulating plasmablasts induce the differentiation of human T follicular helper cells via IL-6 production. J Immunol 194(6):2482–2485
Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T et al (2012) Consensus statement on the pathology of IgG4-related disease. Mod Pathol 25:1181–1192
Engel P, Zhou LJ, Ord DC, Sato S, Koller B, Tedder TF (1995) Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity 3:39–50
Fink K (2012) Origin and function of circulating plasmablasts during acute viral infections. Front Immunol 3:78
Iwata S, Saito K, Hirata S, Tanaka Y (2012) Phenotypic changes of lymphocyte in a patient with IgG4-related disease after corticosteroid therapy. Ann Rheum Dis 71(12):2058–2059
Hamano H, Kawa S, Horiuchi A et al (2001) High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 344:732–738
Hiepe F, Dörner T, Hauser AE, Hoyer BF, Mei H, Radbruch A (2011) Long-lived autoreactive plasma cells drive persistent autoimmune inflammation. Nat Rev Rheumatol 7:170–178
Kaminski DA, Wei C, Qian Y, Rosenberg AF, Sanz I (2012) Advances in human B cell phenotypic profiling. Front Immunol 3:302
Kepler TB, Perelson AS (1993) Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation. Immunol Today 14(8):412–415
Khosroshahi A, Bloch DB, Deshpande V, Stone JH (2010) Rituximab therapy leads to swift decline of serum IgG4 levels and prompt clinical improvement in IgG4-related disease. Arthritis Rheum 62:1755–1762
Khosroshahi A, Carruthers MD, Deshpande V et al (2012) Rituximab for the treatment of IgG4-related systemic disease: lessons from a series of ten consecutive cases. Medicine (Baltimore) 91:57–66
Mattoo H, Mahajan VS, Della-Torre E, Sekigami Y, Carruthers M, Wallace ZS et al (2014) De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. J Allergy Clin Immunol 13:679–687
Mattoo H, Mahajan VS, Maehara T, Deshpande V, Della-Torre E, Wallace ZS, Kulikova M, Drijvers JM, Daccache J, Carruthers MN, Castellino F, Stone JR, Stone JH, Pillai S (2016) Clonal expansion of CD4 cytotoxic T lymphocytes in patients with IgG-related disease. J Allergy Clin Immunol 138:825–838
McHeyzer-Williams LJ, McHeyzer-Williams MG (2005) Antigen-specific memory B cell development. Annu Rev Immunol 23:487–513
Wallace ZS, Mattoo H, Carruthers M, Mahajan VS, Della Torre E, Lee H et al (2014) Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations. Ann Rheum Dis 1–6
Wallace ZS, Mattoo H, Mahajan VS, Kulikova M, Lu L, Deshpande V, Choi HK, Pillai S, Stone JH (2016a) Predictors of disease relapse in IgG4-related disease. Rheumatology 55(6):1000–1008
Wallace ZS, Mattoo H, Mahajan VS, Kulikova M, Lu L, Deshpande V, Choi HK, Pillai S, Stone JH (2016b) Predictors of disease relapse in IgG4-related disease. Rheumatology 55(6):1000–1008
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Lanzillotta, M., Della-Torre, E., Stone, J.H. (2016). Roles of Plasmablasts and B Cells in IgG4-Related Disease: Implications for Therapy and Early Treatment Outcomes. In: Okazaki, K. (eds) IgG4-Related Disease. Current Topics in Microbiology and Immunology, vol 401. Springer, Cham. https://doi.org/10.1007/82_2016_58
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DOI: https://doi.org/10.1007/82_2016_58
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