The Binding Site GmbH

Clonal plasma cells secrete immunoglobulins, each with the exact same amino acid sequence, that are referred to as monoclonal immunoglobulins. The monoclonal heavy chain and light chain secreted from clonal plasma cells have the same molecular mass prior to the addition of post-translational modifications (PTMs) since their amino acid sequences are the same.

To examine the molecular masses of monoclonal light chains and heavy chains isolated directly from the cytoplasm of bone marrow (BM) plasma cells and compare them to the serum derived monoclonal heavy and light chains.

Using immunopurification and LC-MS we compared the molecular masses of immunoglobulins immunopurified from a patient's serum to those immunopurified from the cytoplasm of their BM plasma cells.

Our findings demonstrate that the light chain molecular masses were identical whether they were obtained from serum or plasma cell cytoplasm. However, the heavy chain molecular masses did not match in bone marrow and serum due to differences in glycosylation, a common post-translational modification (PTM) found on the heavy chain.

The data presented here show that by using LC-MS to analyze monoclonal immunoglobulins (also referred to as miRAMM) additional phenotype information is obtained at the cellular level which is complementary to other more common techniques such as flow cytometry and histopathology.

A polemic in response to de Kat Angelino et al (Clin Chem, 2010, 56, 1188-90) is given. Mead and Carr-Smith agree that nephelometric measurement of monoclonal polymerized free light chains (FLCs) cannot be consistently accurate, there are now >200 publications attesting to the clin. value of these assays. However, if alternative assay formats were to be considered for clin. use, confirmation of their utility would be required.