GLOBULINS: LOW, CAUSES, SYMPTOMS AND TREATMENT - MEDICINE - 2025

The globulins are proteins in the human body that help protect it. Some are made in the liver, while others are made by the immune system. The normal globulin concentration in human blood is 2.6-4.6 g / dL.

Low globulins represent a heterogeneous group of diseases in which the globulin fraction of plasma proteins does not reach the minimum values ​​to exert their functions. Globulins are a group of proteins with specific functions that represent 20% of total plasma proteins, the remaining 80% being albumin.

Globulins can be divided into several types, each with a specific role, so a deficiency of a particular globulin will lead to the development of a specific clinical syndrome.

What are globulin tests used for?

There are two main types of blood tests to measure globulins:

-Total protein test: measures globulins and albumin.

-Electrophoresis of serum proteins: measures gamma globulins, in addition to other proteins in the blood.

Globulin tests can diagnose:

• Liver damage or disease.
• Nutritional problems
• Autoimmune disorders
• Certain types of cancer.

Globulin classification

Globulins are divided into different groups, according to their chemical structure and their biological function.

Alpha globulins 1

They include antitrypsin, whose function is to limit the activity of lysosomal enzymes; thyroglobulin, responsible for fixing thyroid hormones; and to the retinol-binding protein, whose function is to transport retinol.

Alpha 2 globulins

They include various types of proteins, among which are alpha 2 macroglobulin, responsible for neutralizing certain proteolytic enzymes; ceruloplasmin, where copper is fixed and transported; haptoglobin, which is involved in the metabolism of the Hem group; and prothrombin, a key protein in the coagulation cascade.

Beta globulins

In this group are hemopexin, which also takes part in the metabolism of the Hem group; and transferrin, essential to fix serum iron and, therefore, essential in the hematopoiesis process. In addition, in this group is the complement C3 complex, a key element in inflammatory processes.

Gamma globulins

This group includes all antibodies secreted by the B cells of the immune system. Also known as immunoglobulins, these proteins are of different types (IgA, IgE, IgG, IgM and IgD), each with specific and clearly differentiated functions in the processes of acquired immunity and immune memory.

Low globulins: associated diseases

By carrying out the proteinogram (fractionated plasma protein levels) it can be determined whether globulin levels are within normal ranges (approximately 20% of plasma proteins).

When this does not happen, it is usually due to a decrease in some of the plasma globulins, which causes a specific syndromic complex according to the committed globulin.

In view of the wide variety of proteins that make up this group as well as their diverse functions, it is impossible to summarize all the diseases associated with globulin deficiencies in a single article.

Therefore, only the most frequent diseases will be mentioned, making a detailed explanation only of the most dangerous condition known as hypogammaglobulinemia.

Thus, in addition to hypogammaglobulinemia (also known as agammaglobulinemia), there are also other clinical conditions associated with a deficiency of a specific globulin, such as:

- Chronic anemia (decrease in transferrin levels).

- Complement C3 complex deficiency disease (extremely rare, manifested by chronic problems related to humoral immunity).

- Alpha 1 antitrypsin deficiency (a life-threatening condition that can lead to the development of pulmonary emphysema and cirrhosis).

- Factor II deficiency of coagulation (this can be congenital or acquired and is associated with hemorrhages derived from the total or partial absence of prothrombin, which affects the normal functioning of the coagulation cascade).

These are just some of the most common conditions associated with globulin deficiency; the list is much longer and exceeds the scope of this entry.

Here is a detailed explanation of one of the most serious medical conditions associated with globulin deficiency: hypogammaglobulinemia.

Hypogammaglobulinemia

As its name implies, it is gamma globulin deficiency or, what is the same, immunoglobulin deficiency.

By not producing enough antibodies, the affected person has problems with acquired immunity, which is manifested by recurrent infections as well as opportunistic and infrequent infections.

This condition is classified as an immunodeficiency, which can be both congenital and acquired.

Causes

In cases of congenital immunoglobulin deficiency (which includes several different types) there are problems with the genetic material that make the B cells unable to produce antibodies.

In these cases, hypogammaglobulinemia appears from the first months of life, the most frequent manifestations being severe and recurrent infections.

On the other hand, acquired hypogammaglobulinemia cases are secondary to other diseases that condition the loss of immunoglobulins, as in the case of non-selective glomerular proteinuria.

Acquired cases can also be due to insufficient synthesis of immunoglobulins due to compromise of the cells responsible for doing so, such as in chronic lymphoid leukemia (CLL) and multiple myeloma.

Symptoms

Hypogammaglobulin deficiency has no specific symptoms of its own. Instead, the cardinal clinical manifestation is the appearance of recurrent infections, often severe and sometimes associated with atypical microorganisms.

Sometimes it can be an asymptomatic and even transitory condition that can go unnoticed, although most cases present with recurrent infections without an obvious cause, which makes the medical team suspicious of the presence of humoral immunity problems.

Diagnosis

The diagnosis of hypogammaglobulinemias is complex and is based on a combination of a detailed medical history, including family history that can guide the diagnosis, combined with specialized laboratory tests, among which are:

- Specific antibody levels.

- Analysis of lymphocyte subpopulations and quantification of NK cells.

- Delayed hypersensitivity tests to known antigens to which the patient has been exposed.

- Evaluation of the humoral function in vitro.

- In vitro cell function studies.

Treatment

The treatment of hypogammaglobulinemia depends on whether it is primary or secondary and, in the second case, on its cause.

Whenever the cause of secondary hypogammaglobulinemia can be corrected, an attempt should be made to do so, which should solve or at least improve the problem.

When it is not possible to do so, as in cases of primary hypogammaglobulinemia, different therapeutic strategies are available, ranging from the parenteral administration of human immunoglobulins, through the transfusion of antibodies through fresh plasma, to the administration of monoclonal antibodies.

Even in selected cases, patients can benefit from bone marrow transplantation.

Each case must be individualized in order to determine the best available treatment depending on the cause of hypogammaglobulinemia and the particular clinical conditions of each patient.

References

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3. Smithies, O. (1957). Variations in human serum β-globulins. Nature, 180 (4600), 1482.
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