Pulmonary manifestations of light chain deposition disease are rare when considering the full disease spectrum of light chain deposition disease pathology. High levels mean the disease is more advanced and may indicate a poor prognosis. Under normal circumstances, these antibodies attach to specific invader antigens and, together with other immune system cells, disable and destroy the antigen andor associated infectious agent or cell. Symptoms, diagnosis, and treatment vary according to the specific disorder. He referred me to my oncologist, who diagnosed me with kappa light chain myeloma. Just checking to see if anyone was diagnosed with this rare disease. The prerequisite for success in this fight is the participation of all health care professionals. Lightchain deposition disease kidney international. Lcs are normally cleared by the kidneys, but in lcdd, these light chain deposits damage organs and cause disease. Treatment of idiopathic light chain deposition disease.
Monoclonal free light chains flcs frequently cause rapidly progressive renal failure in patients with multiple myeloma. Serum neurofilament light chain and longterm disease among. Heavy chain diseases merck manuals professional edition. Light chain deposition disease radiology reference. It is a complex and often fatal disease caused by misfolded protein deposits composed of monoclonal immunoglobulin light chain fibrils in. These pathogenic roles could be relevant to lung disease in alpha 1 antitrypsin deficiency a1atd and chronic obstructive pulmonary disease copd. Very mild cases of pd can be difficult to confirm, even by an experienced neurologist. Immunoassays which provide quantitative measurement of flcs in serum, have now been adopted into screening algorithms for multiple myeloma and other lymphoproliferative disorders. The assays indicate monoclonal flc production by the presence of an abnormal. Light chain multiple myeloma, clinic features, responses to. This booklet focuses on the plasma cell type of mgus, which comprises 85% of all mgus cases.
Aggregation of ig light chains to form amyloid fibrils is a characteristic feature of light chain amyloidosis, a light chain deposition disease. The lightchain deposition disease lcdd belongs to the family of monoclonal immunoglobulin deposition diseases, caused by a dyscrasia underlying plasma. It is recommended for ongoing monitoring of patients with oligosecretory multiple myeloma in which the amount of secreted monoclonal protein is very low, light chain myeloma, light chain al amyloidosis, and lcdd. Frontiers neurofilament light chain as a biomarker in. Light chain disease definition of light chain disease by. Natural history and outcome of light chain deposition disease splitscreen. Infections and infectious diseases are a great burden on many societies, including the countries in the who european region. Al amyloidosis amyloid light chain cleveland clinic. Cast nephropathy occurs in multiple myeloma with massive light chain secretion, and is favored by factors enhancing light chain precipitability, reducing tubular flow, or both. The kidneys are almost always affected and this often leads to kidney failure. The heavy chain diseases hcds are rare b cell proliferative disorders characterized by the production of a monoclonal m protein consisting of a portion of the immunoglobulin heavy chain without a bound light chain. Neuropathy is a process in which multiple nerves become diseased or damaged there are many causes for neuropathy the immune system plays a role, specifically in producing too much of a certain type of protein monoclonal gammopathy 3050% of individuals with waldenstroms macroglobulinemia develop neuropathy most of these individuals have a demyelinating neuropathy which is mild.
Mgrsassociated kidney diseases encompass a wide spectrum of renal pathology and include such lesions as immunoglobulinassociated amyloidosis, the monoclonal immunoglobulin deposition diseases midds. Unicentric castleman disease ucd is localized and carries an excellent prognosis, whereas. Light chain deposition disease lcdd, characterized by the systemic accumulation of immunoglobulin light chains, is most commonly encountered in lymphoproliferative disorders but can also be associated with autoimmune conditions, whilst a few cases are idiopathic. An overview of the kidney and monoclonal free light chains. Light chain al amyloidosis is a rare, heterogeneous condition that affects approximately 812 new individuals per million personyears 1, 2. Variable region of each light chain and heavy chain pair constitutes the antigen binding sites each lc contains 220 amino acids and has a molecular weight of 25kda there is little variation within the constant regions of the and. Prepared by the tufts evidencebased practice center under contract no. Although the diagnosis of lcdd can be suggested from light. Monoclonal gammopathy of undetermined significance mgus facts. Jul 28, 2014 multiple myeloma mm, a malignant lymphoproliferative bcell disease characterized by the accumulation of monoclonal plasma cells in the bone marrow, is the second most frequent hematological malignancy 1, 2.
Less than 5% of patients with light chain amyloidosis involving the heart have isolated cardiac involvement and it is the presence of associated noncardiac symptoms that will point to a systemic disease rather than a purely cardiac pathology. May 15, 2010 monoclonal gammopathy of undetermined significance mgus is a precursor lesion for multiple myeloma mm, an incurable bone marrow malignancy with an annual incidence of approximately 4. Light chain deposition disease restricted to the brain 181 fig. Lightchain deposition disease lcdd is the deposition of monoclonal light chains in multiple organs.
The light chains are secreted by a plasma clone and deposit in the alveolar walls, small airways, and vessels. There are two types of immunoglobulin light chains, kappa. If there is more of one type of light chain than the other, the ratio will be different, which can be a sign of myeloma. Lcdd, which is presently in use, could be replaced by light and heavychain deposition disease.
An in vitro model of light chain deposition disease article pdf available in kidney international 756. Light chain deposition disease is a rather uncommon monoclonal gammopathy with predominantly renal manifestations with presence of monoclonal light. The symptoms a person has vary based on the reason for the light chain production. Light chain deposition disease lcdd is a rare blood cell disease which is characterized by deposition of fragments of infectionfighting immunoglobulins, called light chains lcs, in the body. A case of atypical light chain deposition diseasediagnosis and.
Mar 04, 2020 depth of hematologic response after treatment of al amyloidosis predicts organ response and survival. The most common type of mprotein found in mm is immunoglobulin igg followed by iga and light chain only. See also gammopathy, heavy chain disease, multiple myeloma. Light chain deposition disease blood american society of. In patients with light chain disease, urine mprotein is the main parameter to determine disease status. Amyloid light chain al amyloidosis, also known as primary amyloidosis, is the most common form of systemic amyloidosis in the us.
This issues inaugural conference on light chain deposition disease is discussed by david salant, vaishali. Pdf an in vitro model of light chain deposition disease. It is highly likely that many people have mgus and never know it. It is a rare disease characterized by deposition of nonamyloid immunoglobulin light chains, which do not stain with congo red and do not exhibit a fibrillar structure when examined ultrastructurally. Unusual presentation of light chain deposition disease. While you can have this disease without myeloma, they generally go hand in hand. Light chain deposition disease lcdd in the lung is a rare occurrence. Rheumatoid arthritis and renal light chain deposition disease. Publications home of jama and the specialty journals of the. Monoclonal immunoglobulin deposition occurs in tissues as congo red binding fibrils in light chain amyloidosis, as less structured deposits in light chain deposition disease, and as similar but distinct deposits in light and heavy chain deposition disease.
Circulating free light chains flcs can alter neutrophil migration, apoptosis and activation and may be a biomarker of autoimmune disease and adaptive immune system activation. We report a case of lambda light chain deposition disease in a 35yearold female who presented with acute renal failure requiring hemodialysis. Technically, light chain deposition disease lcdd is not considered a cancer. Using this method, we measured intact immunoglobulin heavylight chain.
Light chain deposition disease accessed 17 january 2018. May 01, 2016 light chain deposition disease lcdd is a rare disease characterized by deposition of monoclonal nonamyloid light chains in multiple organs. I have never heard of light chain deposition disease, but i know that some patients dont show other indicators and have to be checked via light chains. Plasma cell malignancies include a spectrum of diseases, from. Symptoms can be related to the disease as it affects your body as a whole, such as weakness and fatigue, weight loss, bone pain, or numbnesstingling of your arms or legs. The disease is caused when a persons antibody producing cells do not function properly and produce abnormal protein fibers made of components of antibodies called light. Basically, with light chain deposition disease, the kidneys are trying to filter out the abundance of light chain proteins from the blood stream. Light chain deposition disease lcdd is characterized by the deposition of monotypic immunoglobulin light chains in the kidney, resulting in renal dysfunction. High dose chemotherapy in light chain or light and heavy chain. Its a form of multiple myloma, and i was fortunate to have a great doctor in chicago diagnose me. Cr in such patients is defined as a normal flc ratio of 0. The lymphoid type which secretes immunoglobulin m igm and. Lightchain deposition disease accessed 17 january 2018 uncommon. Myeloma patients with sharp serum mcomponents also showed free serum lchains and in 11%, concentrations of the same order of magnitude as was the case in the hypogammaglobulinemic patients.
Learn about amyloid light chain amyloidosis from cleveland clinic. Pdf light chain deposition disease restricted to the. Pdf on aug 1, 2001, p m ronco and others published light chain deposition disease. Prevalence and risk of progression of lightchain monoclonal. Light chain deposit disease lcdd is an uncommon monoclonal gammopathy which should be considered carefully in patients who have both renal disease and a lymphoplasmacytic disorder capable of producing monoclonal light chainsmyeloma, macroglobulinaemia, lymphoma, chronic lymphatic leukaemia 24.
In this scenario, patients should be followed with a serum protein electrophoresis test at six months and, if stable, followed every two to three years until symptoms of multiple myeloma or a related disease appear. If you have problems viewing pdf files, download the latest version. A model of glomerulosclerosis defined at the molecular level find, read. There was no other evidence of a b cell clonal disorder or amyloidosis. Light chain deposition disease lcdd is a rare disease characterized by deposition of monoclonal nonamyloid light chains in multiple organs. A 59yearold male was diagnosed with nephrotic syndrome secondary to light chain deposition disease. Light microscopy features in the present case can suggest several kidney diseases. Assessment of minimal residual disease using multiparametric. Serum free light chain measurement aids the diagnosis of. Pdf light chain deposition disease restricted to the brain. The main role of any additional testing is to exclude other diseases that imitate parkinsons disease, such as stroke or hydrocephalus. They have been explored as potential biomarkers for many years. It is recommended for ongoing monitoring of patients with oligosecretory multiple myeloma in which the amount of secreted monoclonal protein is very low, light chain myeloma, light chain. Natural history and outcome of light chain deposition disease ncbi.
M spike myeloma gamma globulin9,16,30 the presence of any m spike is abnormal and shows the presence of an abnormal clone. Monoclonal gammopathy of undetermined significance. Meaning the association of serum neurofilament light chain level with changes in relevant clinical and neuroimaging outcomes in multiple sclerosis was confirmed, strengthening the potential of this biomarker as a measure of disease activity in multiple sclerosis. A condition in which plasma cells secrete immunoglobulin light chains of only one type, kappa or lambda. Systemic manifestations include weight loss, easy bruising, brittle and.
Consequently, the ratio of kappa to lambda light chains is abnormal in most patients and is a sensitive indicator for this disease. While lcdd can occur in any organ, the kidneys are always involved. Multiple myeloma early detection, diagnosis, and staging. Apr 23, 2012 hevylite is a new, recently developed method that facilitates separate quantification of the kappa and lambdabounded amounts of a given immunoglobulin ig. About one in five people with multiple myeloma produce only light chains. Diabetic nephropathy, amyloidosis, some cases of membranoproliferative glomerulonephritis, fibrillary and immunotactoide glomerulonephritis, and light chain deposition disease lcdd. Light chain deposition disease lcdd is a rare condition characterized by the deposition of specific proteins monoclonal light chains in the kidneys and other organs. People with lcdd make too many light chains, which get deposited in many body tissues. Castleman disease is an uncommon lymphoproliferative disorder characterized as either unicentric or multicentric. Urine mprotein is the amount of free light chains kappa or lambda in the urine.
International myeloma working group updated criteria for. This chapter covers the normal renal handling of flcs and the role of monoclonal flcs in a range of renal pathologies including cast nephropathy, al amyloidosis and light chain deposition disease lcdd. Jan 06, 2012 i cohost a mm support group and may be able to answer some of your questions, or find others who can help. The pathologist viewing the biopsy can tell it is light chain deposition disease because it has a different appearance from other deposition diseases. It is a rare disease characterized by deposition of nonamyloid immunoglobulin light chains, and they do not stain with congo red and do not exhibit a fibrillar structure when examined ultrastructurally. Diagnosis and management of castleman disease jacob d. Monoclonal gammopathy of undetermined significance mgus facts normal plasma cells a type of white blood cell produce antibodies also known as. Neurofilament light chain nfl appears the most promising biomarker in ms patients, and there is now little doubt that nfl should have a role in the followup of ms patients. Light chain deposition disease lcdd is categorized in the family of monoclonal immunoglobulin depo sition diseases midd in the who classification of.
It may be associated with multiple myeloma or other lympho proliferative disease, but many patients have no evidence of any overt plasma cell dyscrasia and the. Serum free light chain assays have been used in a number of published studies which have indicated superiority over the urine tests, particularly for patients producing low levels of monoclonal free light chains, as seen in nonsecretory multiple myeloma and al amyloidosis. Even patients with advanced chronic kidney disease ckd. Light chain and heavy chain deposition diseases plasma cell or rarely lymphoplasmacytic neoplasm that secrete an abnormal light or less often have chain, or both, which deposit in tissues, causing organ dysfunction, but do not form amyloid betapleated sheets. Light chains are used to make antibodies that the body needs to fight infection.
Light chains can be seen in the kidney biopsy tissue using an electron microscope. It is a rare disease characterized by deposition of nonamyloid immunoglobulin light chains, and they do not stain with congo red and do not exhibit a. The most reliable method is by measuring the total amount in a 24 hr urine collection, but it can also be measured in a single sample as gl. Serum free light chain assay14 pages 1112 kappa free light chain 0. Renal lightchain deposition disease lcdd is characterized by the presence of. Aug 02, 2016 light chain deposition disease lcdd is a rare condition characterized by the deposition of specific proteins monoclonal light chains in the kidneys and other organs. Ratio of involveduninvolved immunoglobulin quantification by. The heavy chain in hcd is often incomplete or truncated and a sharp, localized peak may not be seen on the electrophoretic tracing of serum or urine. This test may be used to monitor progression andor treatment. Enlightening light chain deposition disease a related article has been published. Normally, they are present in equal amounts in the blood, giving a ratio of 1 to 1. Immunoglobulin light chain al amyloidosis previously referred to as primary amyloidosis, light chain deposition disease lcdd, and heavy chain deposition disease hcdd are monoclonal plasma cell proliferative disorders that are characterized by tissue deposits of light chain or heavy chain fragments, leading to organ dysfunction.
Sep 26, 2019 light chain deposition disease lcdd is the deposition of monoclonal light chains in multiple organs. Light chain deposition disease is often associated with multiple myeloma or lymphoproliferative disease, but as many as 50% of patients have. Patients with lambda light chain disease have a three times worse prognosis than kappa light chain disease. Lcdd is a clonal plasma cell proliferative disorder in which fragments of light chains. Light chain deposition disease lcdd is a rare illness with, as yet, no clear evidencebased guidelines for its treatment. Newly diagnosed al patients with a visceral disease seen in 20002014 three equallength periods were compared. Vgpr in such patients is defined as a 90% decrease in the difference between involved and uninvolved free light chain flc levels.
Flcs are present in similar concentrations in the vascular and extravascular compartments. We report an unusual histologic manifestation of lcdd in a 55yearold female patient, who presented with nephrotic syndrome and an increased serum creatinine. Light chain deposition disease pulmonary manifestations. Diagnosis and monitoring a case of lightchain deposition. Light chain disease symptoms, causes, diagnosis, and treatment information for light chain disease fanconi syndrome with alternative diagnoses, fulltext book chapters, misdiagnosis, research treatments, prevention, and prognosis. Hlc iggkappa, igglambda, igakappa, igalambda individually, as well as their deriving ratios hlcr in a series of igg or iga multiple myeloma mm patients. In this issue of blood, sayed et al report on a series of 53 patients with light chain lc deposition disease lcdd prospectively followed for a median of 6.
This protein misfolding disorder can affect the heart, kidney, skin, stomach, small and large intestines, nerves, and liver causing these organs and tissues to thicken and eventually lose function. To reduce that burden an integrated approach is required, combining health promotion, disease prevention and patient treatment. Mgus occurs in 3%4% of the population over the age of 50. Al amyloidosis and light chain deposition disease lcdd. Light chain deposition disease lcdd is a rare disease. Light chain deposition disease lcdd is a rare clinical disorder. Persons with light chain disease may develop lytic bone lesions, hypercalcemia, impaired kidney function, and amyloidosis.
Unicentric castleman disease ucd is localized and carries an excellent prognosis, whereas multicentric castleman disease mcd is a systemic disease occurring most commonly in the setting of hiv infection and is associated with human herpesvirus 8. The heavy chain in hcd is often incomplete or truncated and a sharp, localized peak may not be seen on the electrophoretic. The deposition of light chain immunoglobulins mainly affects the kidneys. Light chain deposition disease genetic and rare diseases. Nine of ten living patients showed marked elevations of free serum lchains see table 1 predominantly of one major l chain type. Heavy chain diseases are neoplastic plasma cell disorders characterized by overproduction of monoclonal immunoglobulin heavy chains. Treatment of light chain deposition disease using bortezomib.
Serum free light chain analysis for the diagnosis, management, and prognosis of plasma cell dyscrasias. Monoclonal gammopathy characterized by overproduction and deposition of nonamyloid immunoglobulin light chains in various organs. Aug 02, 2016 technically, light chain deposition disease lcdd is not considered a cancer. We report an unusual histologic manifestation of lcdd in a 55yearold female patient, who presented with nephrotic syndrome and.
1277 775 417 556 1426 345 297 804 1361 809 1493 576 1043 343 1131 1533 1559 1141 793 953 656 1332 970 1394 1217 1488 1100 765 152 269 1443 1465 1226 547