Transferrin-immune complex disease: a potentially overlooked gammopathy mediated by IgM and IgG.

"The combination of marked hypersideremia, hypertransferrinemia and monoclonal gammopathy of underdetermined significance should alert clinicians to the possible presence of an antitransferrin immunoglobin(s), an uncommon acquired disorder also defined as transferrin-immune complex disease. We have previously described a case of transferrin-immune complex disease with 100% transferrin saturation and liver iron overload. However, the findings in the few cases so far reported are heterogeneous and the presence of high transferrin saturation and liver iron overload is not universal. Here, we describe the identification of two additional patients with anti-transferrin monoclonal gammopathy, hypersideremia and hypertransferrinemia but with incomplete transferrin saturation and no hepatic iron overload. The auto-antibodies were purified by using transferrin as affinity bait and characterized. One subject showed a high titer monoclonal anti-transferrin IgM with a κ light chain. The finding is the first observation of IgM autoantibodies against transferrin. The other patient developed the disease after pregnancy. Her monoclonal antibody was an IgG mounting a κ light chain with altered molecular weight. Our results highlight that transferrin might induce the development of a monoclonal immune response of different classes and specificity. The identification, in a single hematologic center, of three different subjects with antitransferrin monoclonal gammopathy suggests that the disease probably represents a still underdiagnosed condition. From a clinical standpoint, these patients must be followed both as MGUS and as hemochromatosis"