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Red cell destruction in cold agglutinin disease
G Zilow1, M Kirschfink, D Roelcke
1Institut für Immunologie, Universität Heidelberg, FRG.
Objective:
The severity of autoimmune hemolytic anemia (AIHA) caused by cold agglutinins (CAs) is known to differ markedly in chronic CA disease as well as in postinfection cold agglutination. The various cold agglutinin specificities and mechanisms of red cell destruction are described.
Data Sources:
Original papers and reviews of the German and English literature (Medline research); own results.
Selection Criteria:
Original papers and reviews of the recent years on studies of the biochemistry and specificity of CAs and the pathophysiology of AIHA.
Results:
A crucial point for the severity of AIHA caused by CAs is the CA-binding capacity to red cells in vivo. This is reflected by the serologic behavior of the actual CA in vitro, represented by its thermal amplitude. Because most CAs are IgM molecules, red cell destruction by CAs is limited to mechanisms initiated by complement (C) activation. In recent years, several CA specificities, in addition to anti-I/i, have been identified on a serological and biochemical basis. CAs of the IgG and rarely of the IgA isotypes have been found.
Conclusion:
The CA-induced red cell destruction does not only depend on CA titer or its thermal amplitude. The severity of CA-induced AIHA may also depend on CA isotype and/or specificity. Therefore, the complement activation capacity of CAs with a given isotype but different specificities has to be elucidated in further studies.