Discussion
Electrophoresis as a technique
The Nobel Prize winning technique of protein electrophoresis was invented by Arne Wilhelm Kaurin Tiselius and has since been modified to allow for the diagnosis of protein disorders such as multiple myeloma and monoclonal, biclonal, or tricolonal gammopathies. Serum immunofixation electrophoresis begins when the serum is placed on a medium such as agar or cellulose and proteins are physically separated by charge, size and shape into different bands by applying an electrical current across the medium. Generally, the most prominent protein subtypes are albumin, the major component and most positively charged, and globulins consisting of alpha1, alpha2, beta1, and beta2 and gamma globulin. The alpha fraction includes alpha1-antitrypsin, thyroid-binding globulin, and acute phase reactants. The beta fraction includes transferrin, IgA, and IgM. The gamma region contains immunoglobulins and gammopathies are defined by peaks or spikes most commonly in the gamma globulin region. To both confirm the presence of the monoclonal immunoglobulin and identify the type of immunoglobulin responsible for the spike, immunofixation can be used. Immunofixation is performed by applying monoclonal antibodies (anti-gamma, anti-mu, anti-alpha, anti-kappa, and anti-lambda) following electrophoresis to detect the gamma heavy chain, mu heavy chain, alpha heavy chain, kappa light chain and lambda light chain. Additional studies such as quantitation of the immunoglobulins and serum free light chain assays to assess the ratio of free kappa and lambda light-chains can be performed. Serum free light chain assays use latex particles coated with purifieid polyclonal antibodies to a number of epitopes on the free light chains that are found in the serum. This then allow for quantification of the kappa and lambda light chains and calculation of their ratio.
Gammopathies
Gammopathies are defined by the abnormal production of antibodies. The most common gammopathy is monoclonal gammopathy of unknown significance (MGUS). MGUS is a premalignant plasma cell dyscrasia that imparts risk for progression to multiple myeloma. Within this category are biclonal and triclonal gammopathies. The most commonly found antibody subtype is IgG followed by IgM. About 3% of cases present with a biclonal gammopathy. These have a similar course and treatment strategy as monoclonal gammopathies. However, as these remain rare, continued investigation is needed to better understand how they may differ from monoclonal gammopathies. Malignant monoclonal gammopathies include multiple myeloma, plasmacytoma, malignant lymphoproliferative disorders, Waldenstrom macroglobulinemia, malignant lymphoma and chronic lymphoproliferative disorders, heavy chain diseases, amyloidosis
Previous reports of triclonal gammopathy
While monoclonal gammopathies and biclonal gammopathies are more commonly identified, triclonal gammopathies remain rare. Cases of tri-clonal gammopathy in the context of a marginal cell lymphoma are even more rare. Previous cases of tri-clonal gammopathy include a case report of a patient who presented with recurrent bleeding and was found to have pancytopenia with immunofixation electrophoresis showing IgM kappa, IgG Kappa and IgA Lambda gammopathy. Other reported cases include in a patient with smoldering plasma cell myeloma, extra nodal non-Hodgkin lymphoma and with plasma cell myeloma, and relapsing multiple myeloma. It has been previously noted that IgG κ, IgG λ, IgA κ are the most common clonal pattern. This current case demonstrates a clonal pattern of IgA lambda, IgM lambda, and IgG lambda.
Patient follow up
The patient was then treated with Zanubrutnib and Decadron with good response. The M-spikes has remained stable with the most recent SPEP demonstrating two spikes of 0.26 mg/dL and 0.13 mg/dL) . Most recent serum free light chains found that lambda light chain was at 172.9 mg/L (RI 5.71 – 26.30 mg/L) and free kappa light chain was at 36 mg/L (RI 3.3-19.4 mg/L) with a free kappa/lambda ratio of 0.21 (RI 0.26 – 1.65). The creatinine stabilized at 2.7 mg/dL (RI 0.5-1.4 mg/dL).
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