Nomenclature of immunoglobulin A and other proteins of the mucosal immune system. IUIS/WHO Subcommittee on IgA Nomenclature.

Terminology/Terminologie Nomenclature of immunoglobulin A and other proteins of the mucosal immune system* IUIS/WHO Subcommittee on IgA Nomenclature1 The predominant immunoglobulin found in exocrine secretions of humans and most other mammals is secretory IgA, a polymeric form of IgA containing an additional glycoprotein chain designated "secretory component". In this article recommended abbreviations are proposed for the following forms of human IgA and other proteins of related interest: secretory IgA, secretory IgM, secretory component, polymeric immunoglobulin receptor, polymeric IgA, monomeric IgA, IgA subclass 1, IgA subclass 2, A2 allotype marker 1, and A2 allotype marker 2. Background and definitions The predominant immunoglobulin found in exocrine secretions of humans and most other mammals is secretory IgA, a polymeric form of IgA containing an additional glycoprotein chain, designated "secre- tory component". Secretory IgM, a form of IgM con- taining bound secretory component, also occurs in secretions, and elevated levels may be present in IgA-deficient humans. Secretory component is syn- thesized in epithelial and glandular cells, in which it is first expressed as a basolateral membrane receptor for J-chain-containing polymeric immunoglobulins, and has therefore been referred to as "polymeric immunoglobulin receptor". During transepithelial transport in endocytic vesicles, polymeric IgA usu- ally becomes covalently linked through formation of disulfide bonds to the secretory component, which is proteolytically cleaved from its transmembrane seg- ment before exocytotic release of the complete se- cretory IgA at the apical surface. IgM is similarly transported to form secretory IgM, except that * Drafted by the Nomenclature Committee of the Society for Mucosal Immunology (SMI), following approval of the proposals by the Board and Membership of SMI at the Ninth International Con- gress of Mucosal Immunology, Sydney, Australia, 27-31 January 1997. This report has been approved by the IUIS/WHO Nomencla- ture Committee. A resum6 in French appears on page 428. Requests for reprints should be addressed to the Chairman of the IUIS Nomenclature Committee, Professor M.W. Turner, Immunobiology Unit, Institute of Child Health, 30 Guilford Street, London WC1 N 1 EH, England. M.W. Russell (Chairman) and M. Gleeson. Co-signatories: P. Brandtzaeg, A. Ferguson, L.A. Hanson, M.E. Lamm, J. Mestecky, I. Moro, B.J. Underdown, and J.-P. Vaerman. Reprint No. 5879 disulfide bonds are not formed with secretory com- ponent. The circulatory form of IgA does not con- tain secretory component, but may occur in both monomeric and J-chain-containing polymeric forms. Although various abbreviations for secretory IgA are in common use, none has been formally recog- nized by the IUIS/WHO Nomenclature Committee. Confusion arises because of the frequent usage of the abbreviation "sIg" for surface immunoglobulin (with isotype designations as appropriate) on B lymphocytes. In humans, two subclasses of IgA are known (IgAl and IgA2), and similar subclasses have been identified in certain other primates (gorilla, chim- panzee, and gibbon). Most other mammals (and other vertebrates in which IgA has been found) have no currently known subclasses of IgA, with the not- able exception of the Lagomorpha (rabbits and their allies), which have 13 subclasses. In addition, human IgA2 exhibits allotypic polymorphism; at least two allotypes that have been defined serologically and at the molecular level are widely distributed in the hu- man gene pool. Additional forms of IgA2 have been described, but it is not clear whether they all repre- sent true allelic variants. Previous reports of the IUIS/WHO Nomenclature Committee have defined subclasses and allotypes of IgG (1, 2), but no formal nomenclature exists for the subclasses and allotypes of IgA. Nomenclature The recommendations (see Table 1) are based upon previously approved nomenclature for Bulletin of the World Health Organization, 1998, 76 (4): 427-428 427 IUIS/WHO Subcommittee on IgA Nomenclature Table 1: Recommended abbreviations for various forms of human IgA and other proteins of related interest S-IgA Secretory IgA S-lgM Secretory IgM SC Secretory component pigR Polymeric immunoglobulin receptor (membrane secretory component) pigA Polymeric IgA migA Monomeric IgA IgAl IgA subclass 1 IgA2 IgA subclass 2 A2m(1) A2 allotype marker 1 A2m(2) A2 allotype marker 2 immunoglobulins, and extend the same principles to the designation of IgA subclasses and allotypes. S-IgA and S-IgM are approved as abbreviations for secretory IgA and secretory IgM, respectively, to avoid confusion with surface immunoglobulins on B cells; accordingly, it is recommended that slg be used to refer to surface immunoglobulins. S also relates to "SC" as the abbreviation for secretory component, which is the distinctive feature of S-IgA (and S-IgM). A significant minority has expressed the view that the hyphenated forms (S-IgA and S-IgM) are unnec- essary, and may choose to use unhyphenated forms (SIgA and SIgM). The occasional practice of abbreviating serum IgA is disapproved as both un- necessary and confusing. The membrane form of se- cretory component, often referred to as polymeric immunoglobulin receptor, may be abbreviated as pIgR in conformity with other receptor nomencla- ture and existing practice. Polymeric IgA, which must normally contain J-chain to be so designated, may be abbreviated as pIgA, and monomeric IgA as mIgA. Although multiple forms of polymeric IgA exist (dimers, trimers, tetramers, and higher forms), it is infrequently necessary to make these distinc- tions, and accordingly it is undesirable to recom- mend standard abbreviations for them. IgA subclass and allotype nomenclature is con- sistent with existing nomenclature for IgG subclasses and allotypes. IgA2 molecules carrying the allotypic markers may be referred to as IgA2m(1) or IgA2m(2). If additional allotypes of human IgA2 are confirmed, their designation should follow the same convention. Where appropriate, these abbreviations, and the conventions on which they are based, should apply to the corresponding proteins of other animal species as well as the human proteins. Resume Nomenclature des immunoglobulines A et autres proteines impliquees dans le systeme immunitaire mucosal L'immunoglobuline la plus abondante des s6- cr6tions exocrines de la plupart des mammiferes et de l'homme est Il'gA s6cretoire, une forme poly- m6rique d'lgA associ6e a une chaine glyco- prot6ique appel6e composant s6cr6toire ou ((piece s6crftoire,>. On propose dans le present article des abr6viations recommand6es pour les IgA humaines et les prot6ines apparent6es suivantes: IgA secr6toire, IgM secr6toire, piece s6cr6toire, recepteur d'immunoglobuline polym6rique, IgA polym6rique, IgA monomerique, IgA sous-classe 1, IgA sous-classe 2, A2 marqueur allotypique 1, A2 marqueur allotypique 2. References 1. Notation for genetic factors of human immunoglobulins. Bulletin of the World Health Organization, 1965, 33: 721-724. 2. Notation for human immunoglobulin subclasses. Bul- letin of the World Health Organization, 1966, 35: 953. 428 WHO Bulletin OMS. Vol 76 1998