ReviewComplement Nomenclature 2014☆
Introduction
In 2009 the International Complement Society (ICS)1 and the European Complement Network (ECN)1 began a joint re-evaluation of the nomenclature for the complement system. Effective communication of scientific results requires terminology that is as simple, as clear and as unambiguous as possible. The last review was published in 1981 (Alper et al., 1981) and much has changed since then. Complement is now known to be initiated by three independent pathways – the classical, alternative and lectin pathways – and many new proteins and receptors have been discovered.
At a meeting in 1963 at the National Institute of Health (Rapp and Borsos, 1963) it was agreed that the components of complement were to be designated by the letter “C”, the prime symbol, and numbers with activated products designated by the letter “a” added to the symbols (as in C′1a for activated C′1 and C′2a for activated C′2). At the time known components consisted of only nine proteins C′1, C′2, C′3, C′4, C′5, C′6 and C′7 with C′1 known to be a complex between C′1q, C′1r and C′1s. The letters q, r and s designated their order of elution from ion exchange chromatography on DEAE-cellulose. In 1968 complement nomenclature was revisited (Austen et al., 1968, Karlson et al., 1981). Among the many changes recommended, was the removal of the prime symbol (C3 instead of C′3) and the extension of the number of proteins to C9. In addition, in recognition of the importance of proteolytic fragmentation it was agreed to use the letters a, b, c, etc. to designate the series of activation fragments deriving from a native component (e.g., C3a and C3b generated from C3). Unfortunately this necessitated a new designation for activated components and it was agreed that a bar over the activated component name would be used to indicate that it was in an activated form ( for C′1a and for activated complexes on cells).
By 1981 an entirely new pathway had been characterized and new proteins and complexes had been described. A subcommittee of the Nomenclature Committee of the International Union of Immunological Societies formalized the nomenclature for this “alternative” pathway of complement activation (Alper et al., 1981). Rather than continue numbering the components beyond C9 it was agreed that the components of this new pathway would be designated by letter symbols except for the C3 protein which was shared with the original activation pathway. The originally described pathway has since been referred to as the “classical” pathway of complement activation. Thus, constituents of the alternative pathway were designated factors B, D, H, I and P plus C3 and enzymatically active complexes were given designations such as C3b,Bb and C3b,Bb,C3b,P.
With the discovery of the lectin pathway and the characterization of many cellular receptors for complement activation fragments an entirely new set of components are now known to be involved in the activation of and the biological responses to complement. As is characteristic of any discovery process the nomenclature used for these new components is not uniform and is often redundant. Thus, the committee1 was charged with conducting the first formal evaluation of complement nomenclature since 1981 and the first set of recommendations are presented in Table 1. As with previous considerations of nomenclature the committee attempted to harmonize and simplify the language of complement while making minimal changes to long established conventions.
Section snippets
Nomenclature for Complement
Table 1 presents the nomenclature for complement proposed by the Complement Nomenclature Committee1 and the boards of directors of both the International Complement Society and the European Complement Network. A consensus on a number of names has still not been reached and these will be the subject of continuing discussion.
Some of the issues resolved include using two letter names for the four pathways and using a hyphen in names for C1-INH, C3a-desArg, C4a-desArg, and C5a-desArg. In the CP the
Concluding comments
While there are many issues remaining to be resolved the active complement committees1 urge authors to use the recommended abbreviations given in Table 1 and in the paragraphs above in their published and presented works. It is critical that reviewers and editors similarly monitor and enforce conformity in the field. This is in the best interest of the clear communication of science both among complement scientists and between this community and related fields of immunology. With the
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