Current Problems of Chronic Cold Hemagglutinin Disease

Protein Abnormalities in the Cold Haemagglutinin Syndrome

“…Determination of the amino acid sequence of the N-terminal end of a cold haemagglutinin K chain further showed that it had a unique sequence and was not detectably contaminated with light chains of different composition (Edman & Cooper 1968). A correlation between amount of cold haemagglutinin protein and cold haemagglutinin titre was found by Fudenberg & Kunkel (1957) in that sera with extreme titres contained large amounts of macroglobulins; exceptions to this have been noticed (Schubothe 1965, Wollheim et al 1967. Many of these experiments were performed with techniques measuring total macroglobulin protein and not only yMglobulin, the protein fraction usually responsible for cold haemagglutinin activity.…”

Cold Agglutinin Disease: Improved Understanding of Pathogenesis Helps Define Targets for Therapy

“…Hexameric IgM has been implicated as playing a pathogenetic role in CAD, although no systematic studies have been published [54]. The activity of CA in plasma or serum at a given temperature is semiquantitatively expressed by the titer, defined by the highest dilution at which agglutination can be seen [10,19].…”

“…CA were discovered in 1903 and related to hemolysis in 1937 [7,8]. Systematic descriptions of CAD appeared in the 1950s-60s [9][10][11], whereas major progress in understanding the pathogenesis and treatment has been achieved during the last 2-3 decades [1,12,13].…”

“…In CAD, a clonal lymphoproliferative disorder (LPD) of the bone marrow, further described below, results in production of CA [18]. Binding of circulating CA to cell surface antigens results in agglutination of erythrocytes and complement-mediated hemolysis, which explain the respective clinical features of CAD [10,19,20]. Thus, two major pathogenetic steps are identified, bone marrow clonal lymphoproliferation and complement-dependent hemolysis, each of which constitutes a logical and feasible target for therapy [18][19][20][21].…”

Autoimmune Hemolysis: A Journey through Time

“…In this period, there were investigations on the properties of the antibodies involved in AIHA. For example, Dacie [ 47 ] reported on the variations in temperature range and pH amplitude of the agglutinating and hemolysing properties of patient sera in CAD, and Schubothe [ 64 ] suggested that the pathological cold agglutinins were modified paraproteins with many individual differences. Immunosuppressive drug therapy was widely employed during this period, in response to the emerging concept that an immunologic inadequacy (failure of immunosurveillance) resulted in a buildup of the cells that make autoantibodies.…”