The term “immunocompromised” defines a health condition with weakened immunity. Immunocompromised patients, such as cancer patients or human immunodeficiency virus (HIV)-positive patients, have a higher susceptibility to acquiring infections and other diseases.

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What are the factors responsible for an immunocompromised condition?

An immunocompromised condition can be induced by many factors and diseases, including cancer, HIV infection, diabetes, certain genetic disorders, malnutrition, organ transplantation, immunosuppressive medicines, and chemotherapy/radiotherapy.

Malignancies

In cancer patients, immunosuppression generally occurs because of a reduction in the number and/or functionality of white blood cells, which are vital immune cells needed to eliminate infections. This can subsequently lead to impaired detection and elimination of abnormal cells. These conditions are particularly common in patients with leukemia, lymphoma, or multiple myeloma.

HIV infection

In HIV-positive patients, immunosuppression is associated with many factors, including impaired innate immune signaling and reduced T cell count and functions. These factors collectively lead to the absence of antibody-mediated neutralization of the virus and effective T-cell memory.

Autoimmune diseases

Autoimmune diseases, such as rheumatoid arthritis and type 1 diabetes, can also induce immunocompromised conditions by modulating the immune system to attack the body’s own healthy cells, tissues, or other components.

Diabetes

In patients with uncontrolled type 2 diabetes, hyperglycemia (high blood glucose level) and insulin deficiency can impair a wide range of immune functions, including cytokine production, leukocyte recruitment, pathogen recognition, complement activation and antibody production, and activation of innate immune cells (neutrophils, macrophages, and natural killer cells).

Collectively, these conditions can significantly increase the susceptibility of diabetic patients to severe infections.

Therapeutic interventions

Radiation therapy and chemotherapy used to destroy cancer cells can induce an immunocompromised condition in patients. Chemotherapy used to prepare cancer patients for stem cell transplantation can significantly suppress the functions of the immune system, making the patients highly vulnerable to infections.

Medicines to treat autoimmune diseases are primarily designed to suppress the immune system and prevent self-attacking. Thus, patients receiving these medicines are expected to have an immunocompromised health condition.

Organ transplantation

Patients undergoing organ transplantation are provided with immunosuppressants to avoid rejection of the transplant by immune cells. These medicines can induce long-lasting immunocompromised conditions. Patients undergoing bone marrow transplantation can also experience immunosuppression in the first few weeks because of the absence of white blood cells.

Age

The functions of the immune system gradually decline with age. Elderly people often experience shrinkage in immune tissues (lymphoid tissue) and a reduction in the number and activity of white blood cells.

Protein-calorie malnutrition

Severe protein deficiency is one of the major causes of immunosuppression. It affects 50% of the socioeconomically deprived population in developing countries. In people with protein-calorie malnutrition, a reduction in protein levels causes a proportional reduction in the number and function of T cells. This makes people highly susceptible to diarrhea and respiratory infections.

How to diagnose an immunocompromised condition?

There is no specific test to detect an immunocompromised condition. A mild form of immunodeficiency can remain unnoticed for years. However, some laboratory tests can be performed to diagnose a possible cause of secondary immunodeficiency.

Antibody test

This test is generally performed to detect the levels of IgA, IgG, and IgM antibodies in the serum. The results are subsequently compared with the antibody levels of age-matched healthy controls to determine the level of immunosuppression.

Antibody production tests are also performed to diagnose immunosuppression. In this case, the patient’s response to common protein antigens (tetanus or diphtheria toxoid) or carbohydrate antigens (Hemophilus influenza type b or pneumococcal vaccine) is determined after immunization.

Blood samples are collected immediately before and about four weeks after immunization and the ability of the immune system to produce antibodies against the tested antigen is determined.

Flow cytometry is performed to estimate the levels of different types of lymphocytes in the blood, including antibody-producing B lymphocytes.

T cell test

The complete and differential blood count is performed to determine the reduction in T lymphocyte (T cells) numbers in the blood. This is an easy and reasonable test to determine T cell deficiency.

Cell-based tests are performed to determine the functions of T cells. In these tests, T cell response to certain types of stimuli (mitogens, tetanus toxoid) is determined by examining the growth and cytokine-producing ability of T cells.

Neutrophil count

Differential white blood cell counts are performed serially to determine the absolute number of neutrophils in the blood. A reduction in absolute neutrophil count (neutropenia) is the most common indicator of immunosuppression.

How to treat an immunocompromised patient?

Treatment of the primary condition is the most useful way to resolve secondary immunodeficiency. The most commonly used treatments against immunodeficiency include lymphocyte infusion and medicines to stimulate white blood cell production.

In patients with HIV infection, antiretroviral therapy is used to improve the number and functions of T cells. This treatment is highly effective in increasing life expectancy and reducing immunodeficiency in patients.

Drug-induced immunodeficiency generally resolves soon after completion of the therapy. Immunosuppressants used to treat organ transplant patients generally have a global impact on the immune system, inducing severe immunodeficiency. With the advancement in medical science, new-generation medicines called biologics have been developed to treat transplant patients.

These medicines, including monoclonal antibodies, have more targeted activity than conventional medicines, and thus, do not affect non-targeted immune cells.

References:

• Demarco, C. (2020). What does it mean to be immunocompromised? MD Anderson Cancer Center. Available at: https://www.mdanderson.org/cancerwise/what-does-it-mean-to-be-immunocompromised-covid-19.h00-159387468.html
• Immunodeficiency. (2017). British Society for Immunology. Available at: https://www.immunology.org/policy-and-public-affairs/briefings-and-position-statements/immunodeficiency
• Berbudi, A., et al. (2020). Type 2 Diabetes and its Impact on the Immune System. Current Diabetes Reviews. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475801/
• Elfaki, MG. (2014). Immunosuppression Induced by HIV Infection. Biology and Medicine. https://www.longdom.org/open-access/immunosuppression-induced-by-hiv-infection-0974-8369.1000e111.pdf
• Laboratory tests. (2013). Immune Deficiency Foundation. Available at: https://primaryimmune.org/about-primary-immunodeficiencies-diagnosis-information/laboratory-tests

Further Reading

• All Immunology Content
• What is Immunology?
• Classical Immunology
• Clinical Immunology
• Developmental Immunology

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.