Immunoglobulin G4: an odd antibody

Clinical and Experimental Allergy - Tập 39 Số 4 - Trang 469-477 - 2009
Rob C. Aalberse1, Steven O. Stapel1, Janine Schuurman2, Theo Rispens1
1Sanquin and Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
2Genmab, Utrecht, The Netherlands

Tóm tắt

SummaryDespite its well‐known association with IgE‐mediated allergy, IgG4 antibodies still have several poorly understood characteristics. IgG4 is a very dynamic antibody: the antibody is involved in a continuous process of half‐molecules (i.e. a heavy and attached light‐chain) exchange. This process, also referred to as ‘Fab‐arm exchange’, results usually in asymmetric antibodies with two different antigen‐combining sites. While these antibodies are hetero‐ bivalent, they will behave as monovalent antibodies in most situations. Another aspect of IgG4, still poorly understood, is its tendency to mimic IgG rheumatoid factor (RF) activity by interacting with IgG on a solid support. In contrast to conventional RF, which binds via its variable domains, the activity of IgG4 is located in its constant domains. This is potentially a source of false positives in IgG4 antibody assay results. Because regulation of IgG4 production is dependent on help by T‐helper type 2 (Th2) cells, the IgG4 response is largely restricted to non‐microbial antigens. This Th2‐dependency associates the IgG4 and IgE responses. Another typical feature in the immune regulation of IgG4 is its tendency to appear only after prolonged immunization. In the context of IgE‐mediated allergy, the appearance of IgG4 antibodies is usually associated with a decrease in symptoms. This is likely to be due, at least in part, to an allergen‐blocking effect at the mast cell level and/or at the level of the antigen‐presenting cell (preventing IgE‐facilitated activation of T cells). In addition, the favourable association reflects the enhanced production of IL‐10 and other anti‐inflammatory cytokines, which drive the production of IgG4. While in general, IgG4 is being associated with non‐activating characteristics, in some situations IgG4 antibodies have an association with pathology. Two striking examples are pemphigoid diseases and sclerosing diseases such as autoimmune pancreatitis. The mechanistic basis for the association of IgG4 with these diseases is still enigmatic. However, the association with sclerosing diseases may reflect an excessive production of anti‐inflammatory cytokines triggering an overwhelming expansion of IgG4‐producing plasma cells. The bottom line for allergy diagnosis: IgG4 by itself is unlikely to be a cause of allergic symptoms. In general, the presence of allergen‐specific IgG4 indicates that anti‐inflammatory, tolerance‐inducing mechanisms have been activated. The existence of the IgG4 subclass, its up‐regulation by anti‐inflammatory factors and its own anti‐inflammatory characteristics may help the immune system to dampen inappropriate inflammatory reactions.

Từ khóa


Tài liệu tham khảo

10.1111/j.1365-2222.1976.tb01901.x

10.1159/000231566

Van der Zee JS, 1986, Serologic aspects of IgG4 antibodies. II. IgG4 antibodies form small, nonprecipitating immune complexes due to functional monovalency, J Immunol, 137, 3566, 10.4049/jimmunol.137.11.3566

10.1042/bj2810317

10.1016/0161-5890(93)90432-B

Schuurman J, 1997, Mouse/human chimeric IgG1 and IgG4 antibodies directed to the house dust mite allergen Der p 2, use in quantification of allergen specific IgG, 27, 1095

Schuurman J, 1999, Normal human immunoglobulin G4 is bispecific, it has two different antigen-combining sites, 97, 693

10.1046/j.0019-2805.2001.01341.x

10.1126/science.1144603

10.1111/j.1365-2222.2007.02883.x

Zack DJ, 1995, Localization of an Fc‐binding reactivity to the constant region of human IgG4. Implications for the pathogenesis of rheumatoid arthritis, J Immunol, 155, 5057, 10.4049/jimmunol.155.10.5057

10.1073/pnas.90.8.3730

Jabara HH, 1993, Sequential switching from mu to epsilon via gamma 4 in human B cells stimulated with IL‐4 and hydrocortisone, J Immunol, 151, 4528, 10.4049/jimmunol.151.9.4528

10.1159/000023918

10.1159/000024099

Punnonen J, 1993, IL‐10 and viral IL‐10 prevent IL‐4‐induced IgE synthesis by inhibiting the accessory cell function of monocytes, J Immunol, 151, 1280, 10.4049/jimmunol.151.3.1280

10.1111/j.1398-9995.2008.01774.x

Satoguina JS, 2005, T regulatory‐1 cells induce IgG4 production by B cells, role of IL-10, 174, 4718

10.1016/j.cellimm.2005.01.001

10.4049/jimmunol.181.3.1767

10.1111/j.1600-065X.2008.00631.x

Platts‐Mills T, 2001, Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen, a population-based cross-sectional study, 357, 752

10.1159/000091169

10.1111/j.1365-2222.2005.02331.x

10.1159/000106318

Akdis M., 2006, Healthy immune response to allergens, T regulatory cells and more, 18, 738

10.1016/S1286-4579(01)01449-6

Platts‐Mills TA., 1979, Local production of IgG, IgA and IgE antibodies in grass pollen hay fever, J Immunol, 122, 2218, 10.4049/jimmunol.122.6.2218

Chapman MD, 1978, Measurement of IgG, IgA and IgE antibodies to Dermatophagoides pteronyssinus by antigen‐binding assay, using a partially purified fraction of mite extract (F4P1), Clin Exp Immunol, 34, 126

10.1007/BF02697369

10.1159/000090277

Kotowicz K, 1993, Human immunoglobulin class and IgG subclass regulation, dual action of interleukin-4, 23, 2250

Fujieda S, 1995, IL‐4 plus CD40 monoclonal antibody induces human B cells gamma subclass‐specific isotype switch, switching to gamma 1, gamma 3, and gamma 4, but not gamma 2, 155, 2318

10.4049/jimmunol.173.7.4529

Aalberse RC, 1983, Serologic aspects of IgG4 antibodies. I. Prolonged immunization results in an IgG4‐restricted response, J Immunol, 130, 722, 10.4049/jimmunol.130.2.722

10.1111/j.1365-2222.1991.tb00809.x

10.1111/j.1365-2222.2007.02749.x

Hussain R, 1992, Control of allergic reactivity in human filariasis, predominant localization of blocking antibody to the IgG4 subclass, 148, 2731

Yazdanbakhsh M, 2001, Th2 responses without atopy, immunoregulation in chronic helminth infections and reduced allergic disease, 22, 372

10.1038/217174a0

10.1055/s-0037-1613257

10.1111/j.1365-2141.2008.07232.x

Wouters D, 2007, Human antichimeric antibodies to infliximab and infusion‐related allergic reactions in patients with rheumatoid arthritis, Allergy Clin Immunol Int, 198

10.1159/000236090

Stapel SO, 2008, Testing for IgG4 against foods is not recommended as a diagnostic tool, EAACI task force report, 63, 793

10.4049/jimmunol.172.5.3252

Lessof MH, 1978, Effects of passive antibody in bee venom anaphylaxis, Johns Hopkins Med J, 142, 1

Aalberse RC, 1983, Clinical reviews in allergy, 289

10.1007/s00403-007-0734-0

10.1111/j.1600-0625.2005.00367.x

10.1056/NEJM198906013202206

10.1016/j.clim.2006.03.006

10.1111/j.1582-4934.2007.00081.x

Neild GH, 2006, Hyper‐IgG4 disease, report and characterisation of a new disease, 4, 23

10.1159/000232784

10.1159/000233000

10.1111/j.1365-2222.1982.tb01643.x

Malbec O, 1998, Fc epsilon receptor I‐associated lyn‐dependent phosphorylation of Fc gamma receptor IIB during negative regulation of mast cell activation, J Immunol, 160, 1647, 10.4049/jimmunol.160.4.1647

Schuurman J, 1998, Complementation of Der P 2‐induced histamine release from human basophils sensitized with monoclonal IgE, not only by IgE, but also by IgG antibodies directed to a nonoverlapping epitope of Der p 2, 101, 404

Mudde GC, 1990, IgE, an immunoglobulin specialized in antigen capture, 11, 440

Van der Heijden FL, 1993, Serum‐IgE‐facilitated allergen presentation in atopic disease, J Immunol, 150, 3643, 10.4049/jimmunol.150.8.3643

Van Neerven RJ, 1999, Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum‐IgE‐facilitated allergen presentation, J Immunol, 163, 2944, 10.4049/jimmunol.163.5.2944

Thông tin
Thông tin xuất bản

Clinical and Experimental Allergy

Tập 39 Số 4

469-477

Thông tin tác giả