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Monoclonal gamopathy, or paraproteinemia, is an excess of myeloma protein, or monoclonal gamma globulin, in the blood. The cause of the illness has not been fully determined. Gammapathies are characterized by the uncontrolled proliferation of plasma cells involved in the synthesis of antibodies and the excessive synthesis of hemoglobin similar to structural proteins.
Monoclonal gynopathies include: multiple myeloma, light chain multiple myeloma, Waldenstrom's macroglobulinemia, non-secretory myeloma, slow-growing multiple myeloma, monoclonal gynopathies of undetermined significance, primary systemic amyloidosis, and light chain accumulation disease.
Immunoglobulin molecules consist of two identical heavy (α, δ, ε, γ or μ) and light (κ and λ) chains. Each light chain is covalently linked to a heavy chain. Also, each heavy chain is covalently bonded to each other.
In healthy people, most of the light chains are in the bound form. In serum, free kappa chains are mainly in the form of monomers, while free lambda chains are bound to the protein as a dimer with a molecular weight of 45 kDa. This causes different filtration in the renal tubules.
As a rule, light chains are filtered in the glomeruli of the kidney and reabsorbed (reabsorbed) in the proximal tubules, which is why their concentration in the urine is very low. However, the production of monoclonal light chains may exceed the ability of the kidney to reabsorb it, causing the light chains to appear in the urine. The detection of monoclonal light chains in urine has been a diagnostic criterion for myeloma since 1847, when this process was described by Dr. H Bence Jonce.
To detect monoclonal gammopathy or plasma cell disorder, protein electrophoresis and immunoelectrophoresis in both urine and blood plasma is necessary. However, monoclonal light chain disease and other pathologies are not often characterized by elevated plasma monoclonal protein levels.
According to the latest studies, the detection of free light chains in the serum allows better management of the patient's condition, compared to other studies, namely:
Preparation of the patient: The study is conducted on an empty stomach
Kappa κ free light chains: 3.3-19.4 mg/l
Lambda λ free light chains: 5.7-26.3 mg/l
Kappa/lambda ratio κ:λ – 0.26 -1.65
If serum kappa κ and lambda λ light chains and their κ:λ ratio are within the normal range and electrophoresis does not show a monoclonal component, the diagnostics of monoclonal gammopathy is most likely excluded.
A change in the κ:λ ratio suggests a monoclonal gammopathy, although a tissue biopsy is necessary to confirm the diagnostics.
An increase in the indicators to the upper limit of the norm may indicate kidney failure and it is necessary to perform kidney function tests.
Reduction of κ-type and λ-type light chains in the blood serum indicates bone marrow dysfunction.
An increase in the index of κ or λ light chains, without violating the k:λ ratio, is caused by the following reasons:
An increase in the index of κ and λ light chains, with pathological values of the k:λ ratio, indicates a combination of gamopathy and kidney failure.
Quantification of monoclonal light chains is important to assess the progression of the disease. Quantitative changes in free light chains reflect changes in the size of monoclonal plasma cells.
Detection of monoclonal proteins in blood serum and urine usually indicates a malignant pathology, however, monoclonal components can be found both in healthy individuals and in benign pathologies.
With multiple greetings In 99% of patients there is an increase of monoclonal protein in blood or urine.
Waldenstrom's disease It is characterized by the necessary presence of IgM monoclonal protein in the serum.
With multiple greetings და with Waldenstrom's disease 75% of patients have the presence of monoclonal light chain Bence Jones protein in the urine.
Multiple myeloma და amyloidosis In cases, it is typical to find free light chains and fragments of heavy chains in the urine.
High levels of polyclonal free light chains characterize autoimmune diseases such as systemic lupus erythematosus.
Kappa
(κ) |
Lambda
(λ) |
κ:λ ratio | Interpretation |
norm | norm | norm | normal serum |
reduced | reduced | norm | Bone marrow suppression without remission |
elevated | Monoclonal gammapathy with bone marrow suppression | ||
reduced | |||
norm | norm | Bone marrow suppression | |
reduced | Monoclonal gammapathy with bone marrow suppression | ||
elevated | reduced | ||
norm | reduced | elevated | Monoclonal gammapathy with bone marrow suppression |
norm | Bone marrow suppression | ||
norm | elevated | Monoclonal gammapathy with bone marrow suppression | |
reduced | |||
elevated | Normal | Polyclonal immunoglobulins or renal dysfunction | |
reduced | Monoclonal gamopathy without bone marrow suppression | ||
elevated | reduced | elevated | Monoclonal gammapathy with bone marrow suppression |
norm | elevated | monoclonal gammopathy without marrow suppression | |
norm | Polyclonal immunoglobulins or renal failure | ||
elevated | norm | ||
elevated | Monoclonal gamopathy with renal dysfunction | ||
reduced |
An increase in the concentration of kappa and lambda light chains may occur in polyclonal hypergammaglobulinemia or in renal failure.
Moderate or severe lipemia may interfere with the study or affect the results.
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