Light chain disease and light chain deposition disease
Introduction
Introduction to light chain disease and light chain deposition disease Light chain disease (LCD) and light chain deposition disease (LCDD) are a kind of abnormal proliferative disease of plasma cells. Light chain disease is caused by abnormal plasma cells producing excessive light chains, and the synthesis of heavy chains is corresponding. cut back. Excessive free light chain fragments appear in large amounts in serum or urine called light chain disease; once the immunoglobulin light chain is deposited in whole body tissues, it causes a corresponding clinical manifestation, namely, light chain deposition disease. basic knowledge Sickness ratio: 0.0001% Susceptible people: no specific population Mode of infection: non-infectious Complications: multiple myeloma nephrotic syndrome interstitial nephritis
Cause
Light chain disease and light chain deposition disease
(1) Causes of the disease
The etiology is still unclear. 80% of patients with LCDD have pathogenic light chain as chain, while amyloidosis is dominated by chain. What is the reason? Alert et al analyzed the light chain of 6 LCDD patients and found that there are common people. The rare VIV variable region, using the genetic engineering technology to link the human light chain V IV variable region to the mouse light chain, can detect the deposition of the light chain in the tissue, suggesting that the VIV variable region participates in the onset of LCDD. The VIV variable region is thought to be involved in the pathogenesis of amyloidosis, which may partly explain why LCDD and amyloidosis cause pathogenic light chains are different. People also found that the 27th light chain variable region (VIV and VI) of LCDD patients And/or the 31 amino acid is leucine, isoleucine or tyrosine, the exact meaning is still unclear, presumably related to the light chain is easy to form granular electron dense, similar to amyloidosis Patients with light chain protein epitopes often have special acidic groups, which are thought to be related to light chain fibrin deposition. 15% to 30% of LCDD patients have low blood and urine light chain concentrations, but there are still light tissues. chain Protein deposition, further studies found that these light chains are modified by glycosylation, it is speculated that glycosylation can promote the deposition of light chain proteins in tissues.
(two) pathogenesis
Its pathogenesis is similar to that of primary amyloidosis, except that the deposited light chain fragment is mainly kappa chain, and it is mainly composed of the light chain constant region, and does not have the biochemical characteristics necessary for the formation of amyloid fiber. LCDD causes The mechanism of glomerular sclerosis is not fully understood. It has been found that mesangial cells of LCDD patients produce TGF- through an autocrine mechanism, which in turn promotes excessive production of matrix proteins such as collagen IV, layer adhesion. Protein and fibronectin, etc.
Prevention
Light chain disease and light chain deposition prevention
The cause of the disease is unknown. When the kidney disease is caused by obvious renal insufficiency, the treatment is often ineffective. The purpose of prevention is to delay the development of the disease and prolong the survival of the patient. The main measures are active anti-infective treatment, strengthening the primary disease and symptomatic treatment. In patients with acute renal failure, in addition to dialysis, plasmapheresis should be performed simultaneously.
Complication
Light chain disease and light chain deposition complications Complications multiple myeloma nephrotic syndrome interstitial nephritis
About 2/3 of LCDD patients with multiple myeloma, the light chain type deposited in the tissue is consistent with the abnormal plasma cell production in the bone marrow. The renal damage complications are mainly nephrotic syndrome, chronic interstitial nephritis and acute and chronic renal function. Not complete.
Symptom
Light chain disease and light chain deposition disease symptoms Common symptoms Bleeding tendency Bone destruction Hypertension bone pain weakness Chronic renal insufficiency Renal involvement Renal damage Renal failure Nephrotic syndrome
The onset of this disease is slow, clinical manifestations of unexplained anemia, fever, weakness, bleeding tendency, superficial lymph nodes and liver, splenomegaly, followed by localized or multiple bone pain, pathological fracture or local tumor, X-ray examination: bone localized bone destruction or defect, easy to combine recurrent breathing and digestive system infection, many LCDD patients will develop obvious myeloma; some patients with LCDD have clear lymphoplasmacy B cell lesions such as lymphoma Or primary macroglobulinemia, even if such patients do not have obvious plasma cell abnormalities, abnormal production of abnormal monoclonal light chains can be seen. Just like primary amyloidosis, the clinical manifestations of LCDD will follow The location and extent of cloned proteins vary from organ to body. Most typical cases have heart, nerve, liver, and kidney involvement, and may also be affected by skin, spleen, thyroid, adrenal gland, and gastrointestinal tract. There are obvious glomerular lesions when affected, more than half of the patients present with nephrotic syndrome, accompanied by hypertension and renal insufficiency, with or without There is microscopic hematuria, which is characterized by renal dysfunction and early appearance, and shows a rapid progress. Some patients may have severe tubulointerstitial lesions, accompanied by renal insufficiency, but less urinary protein, late may be due to free light The chains are deposited in the nephron and cause renal tubular degeneration, atrophy, and chronic renal insufficiency.
In the past 20 years, a small number of cases in China have reported that LCDD causes kidney damage, mainly including nephrotic syndrome, chronic interstitial nephritis and acute, chronic renal failure, and poor prognosis.
Examine
Examination of light chain disease and light chain deposition disease
Routine inspection
1. Blood examination can be seen in varying degrees of anemia, severe anemia in the late stage, white blood cell count can be normal, increase or decrease, platelet count is mostly reduced, and patients with myeloma can have a small number of myeloma cells, patients can appear macroglobulin Hemorrhage, most myeloma patients can be positive for this-peripheral protein.
2. Other hypercalcemia can occur due to extensive destruction of bone. Blood phosphorus is mainly excreted by the kidneys. Therefore, blood phosphorus is normal when kidney function is normal, but blood phosphorus can be significantly elevated in patients with advanced renal insufficiency, due to bone marrow. Tumors are mainly bone destruction, and no new bone formation, serum alkaline phosphatase is mostly normal or slightly increased, which is significantly different from bone metastases.
3. Renal dysfunction can occur when chronic renal insufficiency occurs, BUN>10.71mmol/L (30mg/dl), serum Cr>176.8mol/L (2mg/dl).
4. Urine examination with or without microscopic hematuria, but less urine protein, but the patient can excrete monoclonal light chain protein in the urine, urine protein electrophoresis on albumin is less and globulin is significantly increased.
Kidney biopsy
1. Light microscopy glomeruli can have a variety of manifestations, from normal glomeruli to varying degrees of mesangial widening and mesangial changes, can be seen in LCDD patients, in which mesangial nodular changes More specific, similar to the typical Kimmelstiel-Wilson mesenteric nodular sclerosis in patients with diabetic nephropathy, the difference is that the PAD staining of the mesenteric nodules of LCDD is stronger, while the silver staining is weaker, the Congo red staining is negative, and the latter nodules are uneven. There is a history of diabetes and negative reaction with anti-light chain / antiserum, as well as transparent degeneration of the ball artery wall of the human ball, and the difference with diabetic nephropathy is that the glomerular basement membrane of LCDD under light microscope is not thickened. Other glomeruli may be completely normal or only mild mesangial sclerosis, glomeruli may have capillary microangioma changes, some glomeruli may have membrane proliferative characteristics, renal tubules show thickening of basement membrane, noteworthy Myeloma casts are rarely seen when MM is combined with LCDD.
2. Immunofluorescence immunohistochemical staining of monoclonal light chain antibody shows that / light chain (80% light chain) is deposited in the mesangial area (nodules), tubular basement membrane and vessel wall, complement Ingredient staining of the often negative / light chain diffusely along the tubular basement membrane in a punctate or granular form is characteristic of LCDD).
3. Electron microscopy of the glomerular basement membrane in the sparse layer and mesangial area with granular material deposition, mesangial matrix widening and glomerular basement membrane thickening; renal tubular basement membrane and renal interstitial vascular basement membrane visible dense particle electrons Compact.
4. X-ray examination of common bones localized osteoporosis, osteolytic destruction and pathological fractures.
Diagnosis
Diagnosis and identification of light chain disease and light chain deposition disease
According to the above clinical manifestations and typical pathological features of LCDD renal biopsy, the disease can be diagnosed, but it should be differentiated from primary amyloidosis, heavy chain disease and diabetic nephropathy.
Diagnostic criteria
1. Normal immunoglobulins are unchanged or decreased.
2. The light chain in the blood or urine appears supernormal after electrophoresis.
3. With clinical multiple myeloma symptoms.
4. The urinary-peripheral protein is positive and belongs to the Kappa or Lamdba type.
Differential diagnosis
Light chain disease and light chain deposition disease should be differentiated from primary amyloidosis, heavy chain disease and diabetic nephropathy.
1. LCDD and primary amyloidosis identification points
(1) The LCDD has about 80% of its deposited light chain as a kappa chain, while the latter deposits about 75% of the light chain is a lambda light chain.
(2) The light chain fragment in typical LCDD is the constant region of immunoglobulin, and its typical monoclonal light chain immunofluorescence is strongly positive; while the light chain fragment deposited by the latter is the variable region of immunoglobulin, so its anti- The immunofluorescence of the light chain antibody showed only a weak positive.
(3) The light chain deposition of LCDD is granular rather than fibrillar or -sheet structure, and cannot bind Congo red and thioflavine; the latter's light chain deposition is fiber-like or under electron microscope. The lamellar structure, which can be combined with Congo red, exhibits a green birefringence under a polarizing microscope and combines with thioflavin to produce yellow-green fluorescence.
(4) LCDD is often complicated by multiple myeloma or other diseases such as lymphoma or primary macroglobulinemia, resulting in excessive production of monoclonal light chains.
2. Identification of LCDD and diabetic nephropathy According to the typical medical history of diabetic nephropathy and the pathological characteristics of the above renal biopsy, it is not difficult to identify.
