Monoclonal gammopathy is a collective concept that combines a number of diseases, the appearance of which is based on a violation of the efficiency of B-lymphocytes, leading to persistent pathological secretions of one clone of immunoglobulins or their constituent chains.
Benign and malignant nature of the disease
So, monoclonal gammopathy can be benign when the clonal populations of cells that secrete abnormal immunoglobulins do not tend to multiply and grow uncontrollably or to chaotically increase the production of abnormal proteins.
Pathology can also be malignant, when clonal populations producing an abnormal protein are prone to uncontrolled constant growth, and at the same time to reproduction. As a consequence, the secretion of this protein usually increases.
Malignant forms of monoclonal gammopathy include, for example, Waldenström's macroglobulinemia, a diseaselight chains, etc. The malignant form of the disease is generally less sensitive to chemotherapy compared to most other hemoblastoses.
Causes of pathology
The incidence of this disease increases with age (from one percent in people who are aged 25 to four percent in people over seventy). Monoclonal gammopathy occurs in combination with other pathologies in which the production of the M-protein is caused by antibodies formed in large quantities in response to a prolonged antigenic stimulus.
It is worth noting that benign forms of monoclonal gammopathy often develop as a consequence of chronic overstimulation. The latter just leads to increased reproduction of some clones of plasma cells. For example, this is the nature of benign gammopathy, which is observed after bone marrow transplantation. Much less often, this is fixed immediately after tissue transplantation or in the presence of some chronic infections.
Symptoms
Monoclonal gammopathy is often asymptomatic in humans, although peripheral neuropathies can also occur. Despite the fact that most examples of the disease are benign, in 25 percent of cases this disease can progress to B-cell tumors, and in addition, to myeloma or macroglobulinemia.
Symptoms of monoclonal gammopathy should not be ignored.
Diagnosis
The serum immunoglobulin content is assessed by electrophoresis. Immunoglobulins can move in an electric field at different speeds and form a fairly wide peak in the gamma globulin zone. With the development of monoclonal gammopathy (ICD-10 code - D47.2), the content of gamma globulins in the serum usually increases in humans, and a sharp peak is found on the electropherogram in this area, which is called the M-gradient. Less commonly, it may appear in the area of beta or alpha globulins. The threshold of sensitivity of this method is five grams per liter. The monoclonal form of the M-gradient is confirmed by the detection of one type of heavy and light chains during immunoelectrophoresis. Thus, the M-gradient is evaluated quantitatively (using electrophoresis) and qualitatively (using immunoelectrophoresis).
In the event that the monoclonal nature of secretion has been proven, then it is reasonable to use only electrophoresis in the future. The value of the M-gradient reports the mass of the tumor. The M-gradient is a reliable but mass-specific tumor marker. It occurs not only in monoclonal gammopathy, but also in various lymphoproliferative pathologies. For example, this is observed when a patient has chronic lymphocytic leukemia and cellular lymphoma. It is also fixed against the background of malignant neoplasms in the form of chronic myeloid leukemia, breast and colon cancer, and in addition, against the background of a number of autoimmune pathologies (rheumatoid arthritis, myasthenia gravis, autoimmune hemolytic anemia with coldantibodies). And also with other diseases (cirrhosis of the liver, sarcoidosis, parasitic diseases, pyoderma gangrenosum, Gaucher's disease).
A rare skin disease called Gotgron's scleromyxedema is also usually accompanied by monoclonal gammopathy. With this disease, positively charged immunoglobulin, which carries lambda chains, can be deposited in the dermis. It is not excluded that these antibodies can be directed against some elements of the dermis.
The nature of the M-gradient in different gammopathy is not the same. It represents normal immunoglobulins, abnormal or their fragments. The secretion of individual chains is not excluded: light or heavy. In twenty percent of myeloma cases, only light chains are secreted, which appear in the urine in the form of Jones protein. Some plasma cell tumors (especially solitary bone and soft tissue plasmacytomas) secrete a monoclonal protein in less than a third of all cases.
During the diagnostic process, doctors note that the frequency of secretion of immunoglobulins in the presence of multiple myeloma is proportional to their normal content in the serum.
Treatment
Therapy for monoclonal gammopathy (ICD-10 disease code D47.2) is usually not required, however, given the increased risk of hemoblastoses, patients with this paraproteinemia should be examined regularly. In 47 percent of patients, paraproteinemia can persist for life (but does not cause death). Among sixteen percent of patientsmyeloma develops, and ten percent of the paraprotein level can increase to values that exceed three grams.
It is also worth noting that three percent of patients develop primary amyloidosis along with Waldenström's macroglobulinemia, and other hemoblastoses are observed in the same number of patients. Hemoblastoses can develop in seventeen percent of patients ten years later. They develop in 33 percent twenty years immediately after the diagnosis of the presence of a benign monoclonal gammopathy. Sometimes patients are treated with chemotherapy.
Thus, the primary benign, chronic and asymptomatic condition does not require specific treatment for monoclonal gammopathy. But patients need long-term monitoring of the amount of monoclonal immunoglobulin in the blood. That is, all treatment in this case comes down to waiting and observing.
Monoclonal gammopathy of unknown origin
This gammopathy is often characterized by a potentially malignant tumor of the blood system. The following are the features of this type of pathology:
- With an unclear genesis, the patient may have a benign condition that will be precancerous.
- Risks of the transition of pathology into a tumor depend on the properties of the amount and type of paraprotein produced, and in addition, on the ratio of heavy and light chains.
- The condition can occur as a result of mutations in B-lymphocytes, which are cells that normally produce immunoglobulins, that is, proteins thatthat protect against infections.
- Usually, after twenty years, gammopathy of unknown origin can turn into a tumor in forty percent of patients.
- This type of gammopathy is never treated with chemotherapy.
Characteristics and features of gammopathy of unknown origin
So, we are talking about a biochemical state when there is an abnormal M-protein in the blood, which is an incorrect fragment of immunoglobulin or its light chain, synthesized by one line of plasmacytic cells in the bone marrow. It is called incorrect, since it does not perform any functions useful for the body, acting as a marriage in protein production. In the normal state, its concentration in the blood should be minimal.
In most situations, M-protein levels are low and do not increase over time. But in some situations, it can critically increase, turning into multiple myeloma or other monoclonal gammopathy.
Pathology, which is characterized by an unclear genesis, is characterized by slow division of the plasmacyte clone and the release of M-protein in a low amount. Also, against the background of this disease, there are no signs of multiple myeloma, AL-amyloidosis or other lymphoproliferative ailments.
The frequency of this pathology in the population is about one percent and increases, as a rule, with age. After fifty years, the disease is found in three percent of the population, and among men who are over eighty, every twelfth. Monoclonal gammopathy of uncertain significance accounts for sixty percent of all pathologies of this kind.
Reasons
The causes of this form of gammopathy, as the name suggests, are unfortunately unclear. Only the following risk factors are known:
- First of all, this is age, since the older it is, the higher the likelihood of developing an ailment.
- This disease predominantly affects males.
- Contact with pesticides, meaning agricultural workers are particularly at risk.
- Presence of multiple myeloma or monoclonal gammopathy of unknown origin among close and direct relatives.
To date, it is not exactly established, as a result of which a tumor forms. There is a working hypothesis about a sequential change in the genes that code for the formation of immunoglobulin and the appearance of the M protein. Directly between monoclonal gammopathy and multiple myeloma lies a long path of genetic rearrangement in the plasma cell. Pathology with an unclear genesis suggests a single line of B-lymphocytes that produce more M-protein. Multiple myeloma is called a clone of tumor cells, which is initially only in the bones, and then spreads to other organs.
Classification of pathology
Monoclonal gammopathy of unknown origin in medicine is divided into the following variations:
- Lymphoplasmacytic gammopathy, which very rarely can turn intomultiple myeloma, but can transform into macroglobulinemia or other non-Hodgkin's lymphomas.
- Plasmacytic gammopathy, which is a clonal proliferation of plasma cells.
Diagnosis
As part of the study for monoclonal gammopathy of uncertain MGUS and laboratory tests, patients must undergo the following procedures:
- Compulsory blood test to detect low hemoglobin.
- Renal sampling. Most patients are tested for creatinine to assess kidney function.
- Study of blood trace elements, namely, calcium is analyzed, which is an indicator of bone tissue destruction.
- Performing blood protein electrophoresis along with protein immunofixation.
- Determination of immunoglobulins in the blood.
- Establishment of free light chains in the blood.
- Determination of the amount of beta-2-microglobulin.
Instrumental examinations
As an instrumental study, attention is paid to the following procedures:
- X-ray of the bones of the skeleton, thus, the study of the spine, skull, pelvic bones, hip and knee joints and so on.
- Performance of magnetic resonance examination, which is the gold standard in the diagnosis of bone changes in monoclonal gammopathy. It is worth noting that if pain occurs in any of the bones, magnetic resonance imaging is required.
- Computed tomography firstthe queue is aimed at early detection of other blood tumors into which this disease can progress.
- Performing a sternal puncture or trephine biopsy. This procedure is necessary if you have an abnormal kappa-lambda index or one of the symptoms.
- Carrying out densitometry, that is, assessing bone density.
How is monoclonal gammopathy of unknown origin treated? This pathology does not require treatment. However, sometimes this state of "incomplete he alth" turns into a more serious disease, so you need to be regularly monitored by a hematologist. It may take years of observation before such a transition occurs.
In children
The pathology in question is a localized and usually self-limiting disease in children who are between the ages of five and ten and young adults up to thirty. Often the affected organs in monoclonal gammopathy in children are the bones, and in addition, the lungs. Bone involvement is often prevalent, but involvement of the endocrine glands is often observed. This disease is extremely unfavorable in children who are under the age of two.
Back pain
Back pain with monoclonal gammopathy often occurs in those patients who have tumor growth in the vertebra or in the region of the paravertebral soft tissues. Similar discomfort can also occur in the presence of signs of compression of the roots or spinal cord. As part of the study forto eliminate discomfort, patients are given magnetic resonance imaging, which allows to detect damage to the spinal cord, and in addition, to assess the severity of the pathological condition of the spine.
Reviews of doctors and patients
In reviews regarding support for patients with this disease, doctors write that protein fraction electrophoresis is an indispensable tool for screening and diagnosing malignant forms of monoclonal gammopathy associated with immunoproliferative diseases.
In the comments of patients about this disease, it is noted that it is very important to carry out its early diagnosis and prevention. Specialists emphasize that the widespread use of biochemical tests and blood electrophoresis has led to the possibility of early detection of the disease.
Can you live with monoclonal gammopathy? According to patients, if a person is diagnosed with this disease, as well as after confirming such a diagnosis in accordance with modern requirements, it is recommended to adhere to a certain algorithm for monitoring a specialist. If the patient has no complaints during the first year, a study of the amount of paraprotein is carried out, which must be done every three months. A magnetic resonance study, according to patients, is done every six months. If no increase in the paraprotein is detected, then further studies are carried out every twelve months.
Thus, monoclonal gammopathy (and theiralso called immunoglobulinopathies or paraproteinemia) are a heterogeneous category of diseases characterized by the proliferation of lymphoid cells that secrete immunoglobulins. The main distinguishing feature of such diseases is the production of monoclonal immunoglobulin, which is determined in blood serum or urine.
