Quantitative and qualitative changes in the main blood protein fractions is used to diagnose and monitor the treatment of acute and chronic inflammations of infectious and non-infectious origin, as well as oncological (monoclonal gammopathies) and some other diseases.
Synthesis of immunoglobulin represented with one class, subclass and isotype that include heavy and light protein chains of the same type is increased during the plasma cells clone proliferation. This immunoglobulin migrates in the form of compact band determined in association with other protein fractions during electrophoretic separation of blood serum proteins. This immunoglobulin is called monoclonal immunoglobulin or paraprotein. It is called M-gradient in the serum protein electrophoresis. Paraprotein is a cancer-specific marker for the various hemato-oncological diseases.
Multiple myeloma is a classic hematological disease caused with the plasma cells proliferation that secrete monoclonal immunoglobulin (paraprotein) or fragments thereof. In most cases, paraprotein concentration exceeds 25 g/l at the time of diagnosis.
In case of myeloma, serum paraprotein is most often represented with IgG (60%), less often IgA (20%). The remaining about 20% of cases are Bens-Jones myeloma associated to secretion of free light kappa or lambda chains (20%). In 2–4% of myeloma cases, there may be biclonal paraprotein, represented with immunoglobulins of different classes or one class, but containing light chains of different classes. Changes in paraprotein concentration can be used an indicator of the myeloma treatment response. PP concentration shall be monitored in case of myeloma every 3 months during therapy. If PP concentration dropped below the detectable level, it is advisable to re-measure it after 6 or 12 months.
Waldenstrom's macroglobulinemia is a lymphoma with monoclonal IgM over secretion. Lymphoplasmacytic tumor cells of specific immunophenotype are diffusely distributed in the lymph nodes, spleen and bone marrow. High concentration of monoclonal IgM often exceeds 30 g/l and brings high viscosity of the blood as well as a number of clinical signs, including confusion, blindness, bleeding tendencies, heart failure, and hypertension. Paraproteinemic polyneuropathy, cold hemolytic anemia, and cryoglobulins are common in case of macroglobulinemia. IgM paraproteins are found in 20% of population in case of other types of lymphomas and chronic lymphocytic leukemia whereas paraprotein concentration is usually lower than 30 g/l.
Heavy chain disease (Franklin disease) is associated to IgG-gamma heavy chain synthesis only, without respecting light chain. This extremely rare disease is represented with soft palate edema and lymphoid infiltration. Also alpha heavy chain disease is rarely noted when chronic diarrhea occurs, malabsorption due to lymphoid infiltration of the intestinal wall.
Paraproteinemia detection rate is increased sharply in the population reaching 50 year old and found 4-10% in the population over 65 years old during screening examinations. However, the majority of newly diagnosed paraproteinemias in the general population are asymptomatic monoclonal gammopathies of undetermined origin (MGUO). Paraprotein concentration in MGUO is significantly lower than 30 g/l and usually does not exceed 10-15 g/l. In addition, in case of MGUO the paraprotein is detected in association with polyclonal immunoglobulins, i.e., normal synthesis of other immunoglobulins is not inhibited. The term MGUO indicates the paraproteinemia cases without other signs of oncohematological disease that demand for annual monitoring not to miss the malignancy process. When paraproteins are detected in the population under 50 years old, even more frequent repeated examinations are necessary, since the risk of multiple myeloma is quite high for them. When M-protein concentration is more than 15 g/l regardless of age, it is recommended to conduct an extended examination including electrophoresis of 24-hour urine sample and immunofixation every 3-6 months, since the risk of malignancy is very high. Benign paraproteinemia is highlighted, it is specified with paraprotein preservation without progression to multiple myeloma or other disease within 5 years of follow-up. Paraprotein concentration is usually below 3 g/l in case of transient paraproteinemia.