When possible, the basis for nomenclature and classification of a case of amyloidosis under examination should be the fibril protein making up the amyloid deposits. In many instances, the amyloid fibril proteins are identical with or derived from intact fragments of proteins present in the serum. Such fibril protein precursors should be listed as a second set of data. In cases where the given amyloid protein exists in the form of different types or variants, this should be given as additional information when necessary. A fourth type of information is a description of the disease process affecting the patient (Table 1). [TABULAR DATA 1 OMITTED]
Amyloid and amyloidosis should therefore be classified by the fibril protein. Only proteins which have been characterized by their amino acid sequence and are known to be integrated in the amyloid fibrils should be listed (Table 1). Extrafibrillar proteins, like protein AP (the amyloid P-component), although regularly present in amyloid deposits, are thus excluded. The protein designations and abbreviations are chosen using those accepted in the relevant fields of medicine and the basic sciences. They should also be recognized and understood by clinicians, students, etc.
The capital letter A (for amyloid) should be used as the first letter of all designations for amyloid proteins, followed by the protein designation in abbreviated form without any space after this first letter A. When a given term is abbreviated to one single letter, this should be a capital Roman letter or Greek lower-case letter, e.g., AA, A [Beta]. When a term is abbreviated into an acronym, e.g., transthyretin to TTR, all letters are capitalized. When the spelling of the term is maintained but the word is abbreviated, only the first letter is capitalized (e.g., cystatin to Cys).
Regarding numbers, both arabic and roman numerals are used in accord with the abbreviations/designations widely and traditionally accepted in the scientific world. Subscripts or superscripts are not used in order to simplify typing and use of word processing.
A [Beta] and [Beta] protein precursor ([Beta] PP) are designations for the fibril protein and its precursor in Alzheimer's disease, etc. (Table 1). The recently discovered amyloid fibril protein in the immunoglobulin heavy chain has been given the designation AH.
The term protein precursor (Table 1) refers to the protein from which the actual amyloid fibril protein (normal or variant) is thought to be derived. With the exception of [Beta] protein precursor these amyloid-related proteins can be demonstrated in serum, and in many cases the amyloid protein is a fragment, i.e., an incomplete degradation product of its precursor.
Protein type or variant
These represent a variety of classes and variable subgroups of immunoglobulins, molecular variant related to inherited amyloidoses, and a prohormone (i.e., procalcitonin). Class designation of immunoglobulin chains are given in Greek lower-case letter, gamma-chain subclass in Arabic numerals, and variable subgroups in Roman numerals.
The (single) amino acid substitutions in transthyretin and other proteins that account for the inherited amyloid protein variants are indicated by the amino acid that substitutes for the normal one using the 3-letter code, following one open space after the protein designation. This is followed by a single open space, again followed by the position in the protein (i.e., residue number from the N-terminal) in the respective intact, normal protein where the substitution occurs, e.g., ATTR Met 30. The number of the variant amino acid relates to that in the mature (native) precursor protein, whereas the position in the corresponding amyloid protein, which is a fragment of the precursor, is given in parentheses.
The Table shows only one example of protein type or variant for each amyloid protein. …