Multiple-Myeloma proteins.I. Immunological studies

The designation "gamma-related" will be applied to any protein antigenically related to-i.e., reacting with antiserum prepared against-human plasma y-globulins.Webb, Rose and Sehon (1) and Franklin (2) have described the urinary proteins of y-electrophoretic mobility. They found that these consisted largely of material of lower molecular weight than, but antigenically related to, the 7S y-globulin of plasma. The protein population described in these two papers overlaps that defined in this and a previous paper (3) by its antigenic characteristics. It has been decided to continue the interim definition based on antigenic properties for several reasons. First, it permits a ready and probably significant delineation of the group of proteins. Next, as will be shown, not all of the y-related proteins are of y-electrophoretic mobility, and much of the urinary protein of -y-electrophoretic mobility is not y-related.The urinary y-protein, defined by either electrophoretic or antigenic criteria, is divisible into two fractions (2, 3): one of higher molecular weight, and apparently identical with plasma 7S .y-globulin; the other of lower molecular weight. Resemblances between the latter and Bence Jones proteins have been described (3).The present paper reports further investigations of the low molecular weight y-related protein of urine. This will be referred to as "y-u protein." It is further compared with Bence Jones proteins, it is tentatively identified in normal serum and cerebrospinal fluid, and it is shown that it is probably not merely a breakdown product of larger plasma y-globulin molecules.

Section: Discussionsupporting

confidence: 62%

Further Studies of the Gamma-Related Proteins of Normal Urine

Stevenson¹

1962

“…Measurements of the levels of Types K and L (Types I and II) showed a marked abnormality in the ratio of Type K: L (I:1) immunoglobulins in myeloma serums (Table II). This abnormal ratio is caused by the large amounts of myeloma protein that are either Type K (I) or Type L (II) (35)(36)(37)(38) and by the reduced amounts of normal immunoglobulin. The remaining immunoglobulins of the type not represented in the myeloma protein are found to be reduced (Table II).…”

Section: Resultsmentioning

confidence: 99%

Immunoglobulin changes in disease: quantitation on the basis of heavy polypeptide chains, IgG (gammaG), IgA (gammaA), and IgM (gammaM), and of light polypeptide chains, type K (I) and type L (II).

McKelvey¹,

Fahey²

1965

149

“…The globulins produced by malignant plasma cells are closely related to the normal v-globulins, but immunochemical studies of the antigenic determinants present on myeloma proteins have uniformly shown that myeloma proteins are antigenically deficient when compared to normal y-globulins (1)(2)(3)(4)(5)(6)(7)(8). Similar studies (9)(10)(11)(12)(13) have shown that macroglobulinemic macroglobulins are antigenically deficient when compared to the normal 71-macroglobulins.…”

mentioning

confidence: 99%

“…Systematic differences of another type, however, may also occur within these four major groups.. Two antigenically different groups of Bence Jones proteins have been identified in several laboratories (19)(20)(21)(22)(23). Two types of y-myeloma proteins were identified by Korngold and Lipari (7), and Franklin (24) found two types of 82A-myeloma proteins. The molecular differences within major y-globulin groups has received less attention than the y-, 82A-, yLm-, and BJgrouping, and the presence of two general subdivisions has not been established as a consistent feature of all of the anomalous y-globulin groups.…”

mentioning

confidence: 99%

TWO TYPES OF Γ-Myeloma PROTEINS, Β2A-Myeloma PROTEINS, Γ1-Macroglobulins, AND BENCE JONES PROTEINS IDENTIFIED BY TWO GROUPS OF COMMON ANTIGENIC DETERMINANTS

Fahey

Solomon²

1963

The serum myeloma proteins are characteristic products of malignant plasma cells, and individual myeloma proteins provide an important source of information on the protein-producing capacities (and limitations) of plasma cell clones. The globulins produced by malignant plasma cells are closely related to the normal v-globulins, but immunochemical studies of the antigenic determinants present on myeloma proteins have uniformly shown that myeloma proteins are antigenically deficient when compared to normal y-globulins (1)(2)(3)(4)(5)(6)(7)(8). Similar studies (9-13) have shown that macroglobulinemic macroglobulins are antigenically deficient when compared to the normal 71-macroglobulins. Antigen deletion has been demonstrated to occur with malignant transformation (14), and antigenic deficiency of myeloma proteins could be viewed as reflecting a plasma cell change associated with malignancy. Alternatively, myeloma protein differences may simply reflect differences between normal y-globulin molecules (and between normal plasma cells). Immunochemical studies have not settled this question, although marked variability in the antigenic determinants on individual myeloma proteins has been noted. A number of studies, however, have emphasized systematic differences among the proteins formed in malignant plasma cells. Such proteins are now identified as Bence Jones proteins, y-myeloma proteins, fl2A-myeloma proteins, or yi-macroglobulins on the basis of specific immunochemical and physicochemical properties (15-18). Systematic differences of another type, however, may also occur within these four major groups.. Two antigenically different groups of Bence Jones proteins have been identified in several laboratories (19)(20)(21)(22)(23). Two types of y-myeloma proteins were identified by Korngold and Lipari (7), and Franklin (24) found two types of 82A-myeloma proteins. The molecular differences within major y-globulin groups has received less attention than the y-, 82A-, yLm-, and BJgrouping, and the presence of two general subdivisions has not been established as a consistent feature of all of the anomalous y-globulin groups.In the course of immunochemical studies of y-globulins, differences were observed in the antigenic composition of S pieces obtained by papain digestion of individual myeloma proteins (25,26).In view of previous observations (16,27,28) that the antigenic determinants common to all y-globulin groups were present in the S pieces from y-globulin molecules and that Bence Jones proteins were antigenically related to the S pieces, studies were undertaken to determine whether all four classes of proteins formed in malignant plasma cells could be divided into two groups on the basis of readily identifiable antigenic differences.Two forms of molecules (types I and II) differing in antigenic composition were identified in each anomalous protein group (29). Further studies demonstrated that two sets of antigenic determinants (types I and II) were common to all the y-globulin groups, but that the relative frequency...