Properties and modifications of a cryomacroglobulin possessing cold agglutinin activity

Abstract

synopsisThe physical properties of a pathological +-globulin with cold agglutinin activity and cryoglobulin solubility could be modified by changes in temperature and pH and upon dilution. The type of changes noted appear to simulate those expected in a readily dissociable antigen-antibody complex. Naturally occurring and chemically produced subunits of the +globulin and Fc-fragments of myeloma proteins diminished the cryoproperty of the +-globulin and effected changes in its physical properties but did not alter its cold agglutinin activity. Cryoglobulin properties could be conferred upon some purified +globulins by reacting them with Fc-fragments. Mercaptan dissociation of the cryomacroglobulin produces subunits with loss of the noted activities. Reaggregation of these subunits restores some of the native properties, but variable results which are dependent on the type of mercaptan employed are obtained. Attempts to explain the cold agglutinin activity of +globulin hybrids containing variable amounts of mercaptan-produced active and inert subunits suggest that activity requires two of the five subunits to be derived from the rM-cold agglutinin and to be adjacent to each other.

Monoclonal immunoglobulins in patients with carcinoma of the colon

“…It has been established, mainly on a structural basis, that these proteins represent homogeneous populations of molecules within the generally heterogeneous immunoglobulins of a normal individual [8]. Many monoclonal immunoglobulins have been shown to have antigen-binding activities [23], including binding specificities for gamma globulins [17,18,36], red blood cell antigens of the Ii series (i.e., cold agglutinins) [7,10], rubella virus [33], alpha-2-mac. roglobulin [28], lipoprotein [3], streptolysin [39], phosphorylcholine [6], other bacterial antigens [6], nucleic acid derivatives [27], and a variety of haptens, such as dinitrophenol [2,9].…”

Autoimmune Hemolytic Anemias

“…[100][101][102][103] The latter are most often monoclonal IgM immunoglobulins that, in the cold, either self-associate and precipitate from solution (type I cryoglobulinemia) or precipitate as complexes with polyclonal IgG molecules (type II cryoglobulinemia, often due to a monoclonal IgM rheumatoid factor).…”

Anti-Antibody Activity of a Monoclonal Macroglobulin

“…Samples of macroglobulin or myeloma sera, or purified proteins to be tested for anti-antibody activity, were then added to the tubes in 10 Al volumes, again diluted in BSAbuffer. After mixing, the tubes were incubated at 370C for 2 hr, chilled at 4°C for [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] 16 ,Ag of each of two other IgM proteins gave no enhanced precipitation. Fresh normal rabbit serum in a final concentration of 2.5% also gave significant precipitation of the labeled antigen-antibody complex, but did so in all four assays, in distinction to IgMBrd achieving this in only two cases.…”