We are delighted that our review article has met with such interest. Professor Lisch rightly points out that monoclonal gammopathy per se may be associated with a multitude of disorders (1). The associated disorders, however, do not in themselves allow a diagnosis of MGUS—this requires serum electrophoresis combined with immunofixation. As a potential precancerosis, monoclonal gammopathy of unclear significance (MGUS) describes a state in which the size of the plasma cell clone is by definition not sufficient to enable a diagnosis of a hematological malignancy, such as lymphoma or myeloma. Actually, most patients remain asymptomatic throughout their lives. However, as Professor Lisch comments, a multitude of MGUS-associated disorders exist, in which the “toxic” characteristics of the paraprotein dominates, either because of paraprotein deposits or because of autoantibody activity. In all these disorders, the monoclonal gammopathy causes organ damage in different ways. For this reason, the term “monoclonal gammopathy of unclear significance” should not be used in these cases but be replaced by the term “MGUS-associated disorder” (2, 3). Some examples are, as mentioned in our article on the basis of IgM gammopathy, cryoglobulinemia, neuropathies, POEMS syndrome, or monoclonal gammopathy with renal significance (3). This spectrum also includes the so-called oculopathies in the form of keratopathies, which, however, according to what we know and the publication cited by Professor Lisch, are primarily associated with IgG gammopathy and therefore mostly do not fall into the category of IgM-associated disorders, which are the main focus of our article.
On behalf of the authors
Prof. Dr. med. Christian Buske
CCC Ulm – Institut für Experimentelle Tumorforschung
Klinik für Innere Medizin III, Universitätsklinikum Ulm
Conflict of interest statement
Prof. Buske has received fees for consulting services, lectures, funding for a research project initiated by him, and reimbursement of travel and accommodation expenses from Janssen and Roche. He has also received reimbursement from Roche and Abbvie for participation fees for congresses.
|1.||Lisch W, Wasielica-Poslednik J, Kivela T, et al.: The hematologic definition of monoclonal gammopathy of undetermined significance in relation to paraproteinemic keratopathy (An American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc 2016; 114: T7 PubMed Central|
|2.||Glavey SV, Leung N: Monoclonal gammopathy: The good, the bad and the ugly. Blood Rev 2016; 30: 223–31 CrossRef MEDLINE|
|3.||Grunenberg A, Buske C: Monoclonal IgM gammopathy and Waldenstrom’s macroglobulinemia. Dtsch Arztebl Int 2017; 114: 745–51 VOLLTEXT|