Severe cold agglutinin disease and cryoglobulinemia secondary to a monoclonal anti-Pr2 IgM lambda cryoagglutinin

OBJECTIVE: To present a case of cold agglutinin disease/cryoglobulinemia secondary to a monoclonal anti-Pr2 IgM lambda antibody, and review the literature on the occurrence of this antibody in cold-induced disease and the clinical disease associated with it.

METHODS: Cryoantibody characteristics were evaluated by cold precipitation. The antigen specificity of the monoclonal IgM lambda antibody was evaluated using techniques of selective red blood cell absorption.

RESULTS: In our patient, we were able to identify an antibody with both cryoglobulinemic and cold agglutinin (cryoagglutinin) properties. This antibody was found to be monoclonal IgM lambda with specificity to the Pr2 antigen on red blood cells.

CONCLUSIONS: Monoclonal IgM lambda anti-Pr is a rarely found cold agglutinin antibody. In this report we describe the clinical course of a patient who had this antibody, which not only agglutinated red cells in the cold but also had cryoglobulin properties. The clinical illness of this man was characterized by severe acrocyanosis and digital necrosis with eventual organ necrosis and death. We also review the literature on cold induced disease due to monoclonal anti-Pr IgM lambda antibody. Our patient was found to be unique among the reports reviewed. Our case is the first to report both cold agglutinin and cryoglobulinemic properties with the evaluation of the thermal amplitudes of these activities of the antibody. Also, unlike the lymphoproliferative malignancy observed in the cold agglutinin-associated disease in the other reports, our patient's disease was associated with a monoclonal B-cell expansion on the spectrum between benign monoclonal gammopathy and a low grade lymphoproliferative disorder.