What Are the Different Diseases Associated with Plasma Cells?

Plasma cell disease

Plasma cell disease (ie, plasma cell disease, monoclonal gamma globulin disease) refers to a group of diseases in which a single (monoclonal) plasma cell overproliferates and produces a large number of abnormal antibodies. Plasma cells are derived from a type of lymphocyte in white blood cells and normally produce antibodies to help the body defend against infection. There are thousands of different types of plasma cells in the normal body, which are mainly distributed in the bone marrow and lymph nodes. Each plasma cell divides and proliferates to form a clone, and each clone is composed of many identical cells. A cloned plasma cell produces only one type of antibody.

Introduction to Plasma Cell Disease

Plasma cell disease

plasma cell dyscrasias

Plasma cell proliferative disorders are manifested as a series of pathological and biochemical changes. The cause is unknown and may be related to genetic and viral infections. Plasma cells and immunoglobulins (Ig) are generally not found in peripheral blood, and occasionally found in the blood of patients with rubella, measles, chicken pox, serum disease, chronic infections, and multiple myeloma. Some patients with multiple myeloma may develop a large number of plasma cells in the advanced blood and develop plasma cell leukemia.

Plasma cells exist in lymph nodes, spleen, thymus, bone marrow, intestinal mucosa and other tissues, and account for less than 3% of all nucleated cells in normal bone marrow. Plasma cells are derived from B cells. After being stimulated by antigens, activated B cells develop into plasma cells that can produce and secrete antibodies (that is, immunoglobulins).

Immunoglobulin (Ig) has antibody activity and can specifically bind to the corresponding antigen. It is a class of proteins commonly found in living organisms, collectively referred to as gamma globulin. An international conference convened by the World Health Organization in 1968 decided to use Ig to represent various globulins that have antibody activity or are related to antibodies in animals.

Ig is synthesized by lymphocytes or plasma cells (plasma cells are highly differentiated lymphocytes). Each plasma cell can synthesize only one specific Ig, which has the same immunospecificity, and is called a single cell line or a monoclonal Ig. Antibodies in normal serum are a mixture of 5 types of Ig, and each type of Ig is a mixture of thousands of structurally similar and different.

Monoclonal plasma cells of plasma cell disease proliferate excessively and produce a large number of antibody-like molecules. Because these plasma cells and the antibodies they produce are abnormal, they cannot help the body defend against infection. In addition, the production of normal antibodies is usually reduced, making the body more susceptible to infection. An increasing number of abnormal plasma cells can invade and damage various tissues and organs. Plasma cells of uncharacterized monoclonal gamma globulin are abnormal but not neoplastic (malignant). Patients produce a large number of abnormal antibodies but usually do not cause significant clinical manifestations. The disease is often stable for many years, with some patients as long as 25 years without treatment. The disease is more common in the elderly. For unknown reasons, 20% to 30% of patients can develop into plasma cell malignancies such as multiple myeloma. Multiple myeloma can occur suddenly and often requires treatment. Another plasmacytosis macroglobulinemia can also develop from uncharacterized monoclonal gamma globulin.

Plasma cell disease classification

There are two types of malignancy and unknown nature: Malignant. Multiple myeloma, the typical cases are IgG type, IgA type, IgD type, IgE type, free light chain type; atypical diseases such as solitary skeletal plasma cell tumor, extramedullary plasma cell tumor, plasma cell leukemia, non-secretory wall Denstrom's macroglobulinemia, heavy chain disease, amyloidosis. The nature is unknown. Benign monoclonal gamma globulin disease; concurrent with other malignant diseases, especially intestinal cancer, biliary cancer, breast cancer, kidney cancer; concurrent with chronic infections, such as osteomyelitis, tuberculosis, and rheumatoid arthritis.

Plasmacytopathology and clinical manifestations

Increased monoclonal immunoglobulin (Ig) and / or its components are excreted from the body, and its pathophysiological changes lead to a series of clinical manifestations (Table 1 [Pathophysiology and clinical manifestations of monoclonal immunoglobulin]).

Plasma cell disease diagnosis

Pathological examination of living tissues and hematological examination of bone marrow fluid smears are the main basis for diagnosis. The determination of Ig in serum is specific to the diagnosis. The commonly used inspection methods are: Total serum protein. Using a refractometer can measure whether the total amount of protein in the serum (including Ig) is increased. serum protein electrophoresis. The patient's serum was placed in cellulose acetate or agarose medium, and its pH was adjusted to 8.2 to 8.6. After energization, except for IgG, all serum proteins were negatively charged and moved toward the anode, while IgG stayed in place or moved toward the cathode. According to the different swimming speeds of various proteins, the components are separated, and dyed with protein binding dyes, you can identify the five parts of albumin and globulin, and (see Figure [normal people and plasma cells Serum protein electrophoresis of patients with the disease]) immunoelectrophoresis. For analysis of various proteins separated by electrophoresis, immunoprecipitation can be used. The patient's serum is subjected to protein electrophoresis, and then multivalent antiserum (normal human serum after immunizing experimental animals) is dispersed into the electrophoresis line, and a series of precipitates can appear.

Line to identify various Ig. Turbidimetric method. The above two methods of determination can only be qualitative. For quantification of various types of Ig, immunoprecipitation technology is used. The principle is that after the antigen (Ig to be measured) interacts with a certain amount of specific anti-Ig antibody, a precipitate is generated that is proportional to the amount of antigen in the specimen. This method is relatively simple and can be automated. For technical reasons, the lack of IgA can be missed. Another disadvantage of this method is the inability to identify monoclonal or polyclonal Ig. If the result of the determination is that IgG 2000 mg / dl may be an increase in polyclonal IgG. As seen in chronic infection, it may also be monoclonal IgG produced by plasmacytoma. In fact, protein electrophoresis is used to establish and continue to observe changes in monoclonal proteins, while turbidimetry is used to determine the type of monoclonal protein. Other methods, although other laboratory tests are not specific, but also help to understand the increase of Ig in the blood. For example, the erythrocyte sedimentation rate in plasma can be increased due to the increase of IgG, A, or M, which makes red blood cells easy to form a string of money. The degree of increase is directly proportional to the increase of Ig. The viscosity of a patient's serum can be determined by the speed at which the serum flows through the graduated capillary.

Plasma cell disease treatment

There is no cure for this disease. Chemical drugs can kill the continuously proliferating malignant cells and reduce the production of abnormal immunoglobulins. Phenylalanine nitrogen mustard, nitrogen methyl, cyclophosphamide, prednisone, methyl benzylhydrazine, doxorubicin, carbamate, etc. all have certain curative effects, and the effect of the combination medication is better. Patients with tumors and macroglobulinemia can indeed prolong survival.

For patients who have had bone involvement, local radiation therapy can reduce pain and relieve symptoms. Plasma exchange can temporarily reduce the concentration of abnormal proteins in the plasma, and alleviate or disappear related symptoms in a short period of time.

Maintaining regular physical activity and proper fluid intake can not only prevent skeletal complications, but also prevent or reduce the symptoms of hypercalcemia, hyperuricemia, and azotemia.

Plasma Cell Disease Induced Disorder

Plasma cell disease multiple myeloma

Multiple myeloma is a malignant tumor of plasma cells. Monoclonal abnormal plasma cells proliferate, form tumors in the bone marrow, and produce a large number of abnormal antibodies that accumulate in the blood or urine. Multiple myeloma accounts for about 1% of all malignancies in the United States; there are approximately 12,500 new cases each year. This uncommon malignancy has a similar proportion of men and women and is common in people over 40 years of age. The cause is unknown.

Plasma cell tumors most often affect the pelvis, spine, ribs, and skull. Occasionally, other areas are affected, especially the lungs and reproductive organs.

Abnormal plasma cells almost always produce a large number of abnormal antibodies, and the production of normal antibodies is reduced. As a result, patients with multiple myeloma are particularly vulnerable to infection.

Fragments of abnormal antibodies are often excreted by the kidneys and can damage the kidneys and sometimes cause renal failure. Deposits of abnormal antibody fragments in the kidney or other organs can cause amyloidosis in another serious disease (see section 142). Abnormal antibody fragments in urine are called Ben-Chou proteins.

. Symptoms and diagnosis

Sometimes multiple myeloma can be diagnosed before the patient is symptomatic, for example, when X-rays are taken for other reasons, and the disease is typically diagnosed as a skeletal worm.

Multiple myeloma often causes bone pain, especially the spine and ribs, as well as causing bone fragility, which is prone to pathological fractures. Although bone pain is often the initial symptom, the disease can occasionally be diagnosed due to anemia (ie, too few red blood cells), repeated bacterial infections, or renal failure. Anemia is caused by abnormal plasma cells occupying the normal cells that produce red blood cells in the bone marrow. Bacterial infection is because abnormal antibodies are not effective in preventing infection. Renal failure is caused by fragments of abnormal antibodies (ie, Ben-Chou's protein) that damage the kidneys.

In a small number of cases, the blood supply to the skin, fingers, toes, and nose is affected due to thick blood (hyperviscosity syndrome). Insufficient blood supply to the brain can cause neurological symptoms such as confusion, visual abnormalities, and headaches.

Some hematology experiments can help diagnose the disease. A comprehensive blood count can detect anemia and abnormal red blood cell morphology. The rate of red blood cell sedimentation (erythrocyte sedimentation), which reflects how quickly red blood cells settle at the bottom of the test tube, is usually abnormally elevated. One third of patients with this disease have elevated blood calcium due to calcium release into the blood due to skeletal lesions (see section 137). However, the most critical diagnostic experiments are serum protein electrophoresis and immunoelectrophoresis, which can be used to find and identify abnormal antibodies that best explain the problem. 85% of patients with this disease can find this abnormal antibody. In addition, urine electrophoresis and immunoelectrophoresis can detect Ben-Chou protein in 30% to 40% of patients with multiple myeloma.

X-ray examinations often show reduced bone density (osteoporosis) and skeletal erosion. Take a bone marrow specimen with a fine needle and a syringe for examination under a microscope, that is, a bone marrow biopsy (see section 152). It can show that a large number of plasma cells are arranged in flakes and clusters with abnormal plasma cell morphology.

Treatment

The purpose of treatment is to prevent and reduce symptoms and complications, kill abnormal plasma cells, and delay disease progression.

Strong painkillers and radiation therapy for affected bones help reduce severe bone pain. Patients with multiple myeloma, especially those with Ben-Chou's protein found in the urine, need to drink a lot of water to dilute the urine and prevent dehydration, which may aggravate renal failure. Staying active is very important, prolonged bed rest will only increase osteoporosis and make fractures more likely. However, because patients have weak bones, running and weight-bearing activities should be avoided.

Patients with infections such as fever, chills, or skin redness should see a doctor immediately because antibiotics are needed. Although erythropoietin, a drug that stimulates the production of red blood cells, is effective in treating anemia in some patients, patients with severe anemia need red blood cell transfusions. Hypercalcemia can be treated with prednisone and intravenous infusions, and sometimes with calcium-lowering drug bisphosphate. Allopurinol is beneficial for patients with hyperuricemia.

Chemotherapy delays the progression of multiple myeloma by killing abnormal plasma cells. The most commonly used chemotherapy drugs are melphalan and cyclophosphamide. Since chemotherapy kills abnormal cells and reduces the number of normal cells, blood monitoring should be closely monitored. When the decrease in the number of normal white blood cells and platelets is too obvious, the dose of the chemotherapy drug should be adjusted. Corticosteroids such as prednisone or dexamethasone can also be used as part of chemotherapy drugs. For patients who respond well to chemotherapy, interferon can make the response longer lasting.

High-dose chemotherapy combined with radiation therapy is still experimental. Because the toxicity of combination therapy is too large, hematopoietic stem cells should be collected from the patient's blood or bone marrow before treatment, and then returned to the patient after treatment. Generally, this treatment is reserved for patients under 50 years of age.

At present, there is no way to cure multiple myeloma. However, the above treatments can delay the progression of more than 60% of patients. Patients who respond to chemotherapy after diagnosis of this disease are expected to survive 2 to 3 years, sometimes longer. Occasionally patients with multiple myeloma who have been successfully treated for many years have developed leukemia or fibrosis in the bone marrow. Such advanced complications may be related to chemotherapy and often cause severe anemia and increased susceptibility to infection in patients.

Plasmacytosis macroglobulinemia

Macroglobulinemia (also known as Waldenström's macroglobulinemia) is a disease in which a large number of macroglobulins (ie, giant antibodies) produced by plasma cells are accumulated in the blood. Macroglobulinemia results from abnormal tumorous lymphocytes and clonal proliferation of plasma cells. More men than women, the average age of 65 years. The cause is unknown.

. Symptoms and diagnosis

Most patients with macroglobulinemia have no symptoms. Others due to the large amount of macroglobulin in the blood, the blood becomes viscous (hyperviscosity syndrome), reduced blood supply to the skin, fingers, toes and nose, and various other symptoms, including), fatigue, weakness, headache, Dizziness and even coma. Sticky blood can also aggravate heart disease and cause increased intracranial pressure. The small blood vessels behind the eyes fill up and bleed, causing damage to the retina and vision.

Patients with macroglobulinemia can also develop lymphadenopathy, rash, liver and spleen growth, repeated bacterial infections, and anemia.

Macroglobulinemia often causes cryoglobulinemia, a disease characterized by cryoglobulin. Cryoglobulin-type abnormal antibodies, when cooled to normal body temperature, agglutinate in the blood (forming solid particles), and then dissolve after heating. Cryoglobulinemia patients are very sensitive to cold, and Raynaud's phenomenon can occur. Patients' hands and feet become very painful and pale when exposed to cold weather.

Hematology experiments can find abnormal manifestations in patients with macroglobulinemia. The number of red blood cells, white blood cells, and platelets decreases, and the rate of red blood cell sedimentation (erythrocyte sedimentation), which reflects how quickly red blood cells settle at the bottom of the test tube, usually increases. The blood coagulation test results are abnormal, and other experiments can detect cold globulin. Ben-Chou protein (fragment of abnormal antibody) can be detected in urine. But the most useful diagnostic tests are serum protein electrophoresis and immunoelectrophoresis, which detect a large number of abnormal macroglobulins in bleeding specimens.

X-ray examination showed a decrease in bone density (osteoporosis). Bone marrow specimens are collected with fine needles and syringes and examined under a microscope, a bone marrow biopsy, which can show an increase in the number of lymphocytes and plasma cells, which can help confirm the diagnosis of the disease.

. Prognosis and treatment

The course of this disease varies from person to person. Even without treatment, most patients can survive for 5 years or more.

Patients with bloody macroglobulinemia should immediately undergo plasmapheresis. Plasma exchange is a treatment that draws blood, removes abnormal antibodies, and returns red blood cells to the body. Tumorine, a drug commonly used in chemotherapy, can slow the growth of abnormal plasma cells, but cannot cure the disease. Melphalan, cyclophosphamide, and other drugs can also be used alone or in combination.