What Is Light Chain Deposition Disease?
Light chain deposition disease (LCDD) is a rare condition characterized by the deposition of specific types of proteins called monoclonal light chain proteins in different body organs, especially affecting the kidneys. It is classified under monoclonal immunoglobulin deposition diseases by WHO (World Health Organization) and is one of the most common monoclonal immunoglobulin deposition diseases.
What Are Light Chain Proteins?
Light chain proteins are produced by a special type of white blood cell called plasma cells. Plasma cells produce antibodies which are made up of two types of proteins called light chain and heavy chain proteins. They unite together to form a Y-shaped structure called antibodies. These immunoglobulins play a major role in the body’s defense mechanisms. Light chains are made up of two immunoglobulin domains called kappa and lambda chains.
What Are Free Light Chain Proteins?
Free light chain proteins are nothing but excess light chains present in the blood. These excess light chains do not bind with the heavy chains, and they get deposited in various organs of the body. This could be evidenced in plasma cell diseases where there is excessive production of light chains by the plasma cells.
Why Are Kidneys Commonly Affected by Light Chain Deposition Disease?
It is reported that the kidneys are the most commonly affected organ in the body due to LCDD. The reason is the fact that the excessive immunoglobulin light chains produced by the plasma cells are released in the blood in the form of free light chains. These free light chains are cleared from the blood and filtered by the kidneys involved in the filtration of the blood. Therefore, these excessive light chain proteins get deposited primarily in the kidneys causing damage to the organelles of the kidney, such as glomeruli, renal tubules, etc., diminishing its function.
What Are the Types of Light Chain Deposition Disease?
LCDD is categorized into two types, that includes:
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Renal Light Chain Deposition Disease: Studies report that around 65 % of patients affected with LCDD show renal manifestations.
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Extra-renal Light Chain Deposition Disease: Studies report that around 35 % of patients show extra-renal manifestations, affecting other organs. The organs affected commonly other than kidneys include the liver and heart.
What Is the Pathogenesis of Light Chain Deposition Disease?
The suggested pathogenesis of light chain deposition disease is that thefree light chains in the blood would reach the kidneys for the filtration process. The free light chains which are filtered by the glomeruli are reabsorbed by the mesangial cells of the kidneys. Mesangial cells are the specialized cells that secrete certain mediators, enzymes, and extracellular matrix to support the glomeruli. When the mesangial cells are exposed to the free light chains in the blood, the transforming growth factor- B (TGF- B) is activated, thereby increasing the secretion of the extracellular matrix.
The reabsorbed light chain proteins would gradually get deposited in the mesangium of the kidneys. The continuous deposition of the extracellular matrix proteins and the light chain proteins would contribute to the mesangial expansion of the glomeruli. As a sequela of this process, the renal capillaries and the tubular basement membrane of the kidneys also show thickening. The interstitium might demonstrate inflammation and fibrosis (deposition of fibers along the interstitium of the kidneys).
What Is the Etiology of Light Chain Dep.osition Disease?
The exact etiology of light chain deposition disease is unknown; in 50 % of cases, it may occur secondary to a spectrum of disorders called plasma cell dyscrasias, and it includes:
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Multiple Myeloma - This is a white blood cell cancer affecting the plasma cells in which plasma cells produce abundant monoclonal light chains.
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Waldenstrom's Macroglobulinemia - This is a white blood cell cancer characterized by the monoclonal proliferation of B lymphocytes. B lymphocytes differentiate into plasma cells, and this, in turn, may contribute to the light chain deposition disease.
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Monoclonal Gammopathy of Undetermined Significance (MGUS) - This is characterized by the abnormal production of monoclonal proteins in the blood.
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Lymphoproliferative Disorders (LPD) - This is a group of diseases characterized by the abnormal and excessive production of lymphocytes causing monoclonal lymphocytosis, thereby resulting in light chain deposition disease.
What Are the Signs and Symptoms of Light Chain Deposition Disease?
Kidneys are most frequently affected by this condition, and the symptoms include:
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Proteinuria - Presence of protein in the urine.
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Hypertension- Increased blood pressure.
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Microhematuria- This is the presence of blood in the urine, which can be identified only under the microscope.
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Portal Hypertension- This is characterized by elevated pressure in the portal venous system.
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Hepatomegaly- Enlargement of the liver due to the deposition of free light chains.
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Arrhythmias- This is characterized by irregular heartbeat resulting from a block or obstruction in the vessels supplying the heart.
How Is Light Chain Deposition Disease Diagnosed?
The steps in diagnosis include:
1. Presence of Underlying Diseases: The presence of any underlying conditions like multiple myeloma and any type of lymphoproliferative disorders should be considered to understand the cause of light chain deposition disease.
2. Blood Test: It is done to detect the presence of monoclonal light chain proteins in the blood.
3. Urine Test: It is done to evaluate the excretion of monoclonal light chain proteins in the urine.
4. Liver Function Test: It involves a group of blood tests, such as prothrombin time, activated thromboplastin time, albumin, bilirubin, etc., to determine the functional state of the liver.
5. Kidney Function Test: A kidney function test will provide details about the functional status of the kidneys.
6. Ultrasound Abdomen: Ultrasonographic examination of the abdomen would reveal the enlargement of the liver and abnormalities in other organs if affected.
7. Computed Tomography (CT) or Magnetic Resonance Imaging (MRI): This will help visualize renal thickenings, liver enlargement, etc.
8. Kidney Biopsy: Microscopic examination of the biopsied kidney tissue would help confirm the diagnosis of light chain deposition disease.
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Light Microscopic Findings: The hematoxylin and eosin-stained sections of the kidney would reveal the presence of nodular mesangial expansion of the glomeruli, focal irregular thickening of the glomerular capillaries, and the thickening and wrinkling of the glomerular basement membrane. Special stains like periodic acid schiff (PAS) will stain the light chain deposited areas. Congo red staining shows negative results suggesting the non-amyloid nature of the deposits.
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Immunofluorescence Findings: It is one of the vital steps in diagnosing LCDD as immunofluorescence findings would reveal the deposition as light chain proteins along the basement membrane, peritubular regions, renal capillaries, mesangial nodules, and the interstitium.
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Electron Microscopic Findings: Electron microscopic findings would provide a much more detailed picture of the deposits in the kidney. It will show the presence of non-fibrillar, electron-dense amorphous deposits in the glomerular basement membrane and the tubular basement membrane. In eight percent of cases, fibrillar structures are seen gradually replacing the normal matrix of the kidneys, destroying the renal architecture.
How Is Light Chain Deposition Disease Treated?
The main aim of the treatment is to reduce or inhibit the production of the immunoglobulin light chain and its deposition in the organs. The treatment methods include:
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Chemotherapy- Drugs like Bortezomib and Melphalan can be used to reduce the production of immunoglobulin light chains.
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Immunomodulatory Drugs - Drugs like Thalidomide and Lenalidomide can be used to suppress the response of the immune system.
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Autologous Stem Cell Transplantation- This is a procedure in which the patient's own healthy stem cells are collected before the treatment and then reinjected into the patient's body after treatment. This helps in the production of healthy immunoglobulins and prevents the excessive production of light chains.
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Dialysis- Can be considered in patients with renal dysfunction to remove the excess light chains.
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Renal Transplantation - It is advised in patients with renal failure after treating the underlying disease causing excessive light chain production.
What Are the Complications of Light Chain Deposition Disease?
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Chronic Kidney Disease- Patients may develop the symptoms of chronic kidney disease as the deposition of free light chains in the kidney continues.
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Renal Failure- Patients may progressively develop renal failure as a consequence of diminished kidney function and damaged parts of the kidney.
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Liver Failure - Continuous deposition of light chains in the liver would contribute to liver failure.
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Congestive Heart Failure- The heart fails to function as a result of deposition of the free light chains in the blood vessels, causing an obstruction.
Conclusion:
Light chain deposition disease is a rare multi-organ disorder predominantly affecting the kidneys. The prognosis of this condition is reported to be poor as it results in organ failure. Recently with the introduction of novel treatment methods, it has been found to show a better prognosis. However, the recurrence rate of this condition is found to be a little high as it may occur as a result of the underlying cancerous conditions. Hence regular follow-up of the patient and prophylactic measures are necessary to prevent the recurrence of the condition.
