Nucleic acid, antigen, antibody, what are they?

Author: Guo Pengfei, Shanghai Tenth People's Hospital

Reviewer: Yu Lei, Deputy Chief Technician, Shanghai Tenth People's Hospital

I believe that the three-year COVID-19 pandemic has left a mark on everyone's heart. We have become familiar with the processes of nucleic acid collection and antigen testing, and have been exposed to the concepts of nucleic acid and antigen.

In addition, people often encounter the test of "×× antibody" in the diagnosis of colds, fevers and some diseases. So, what are nucleic acids, antigens and antibodies? What do negative and positive results mean? Let's learn about it together.

1. Nucleic Acid: Carrier of Biological Genetic Information

Nucleic acid is the "code book" of life and a biological macromolecule. It is divided into two major families: deoxyribonucleic acid and ribonucleic acid. Their English abbreviations are the familiar DNA and RNA.

DNA is the genetic material of most organisms, and contains the genetic information of organisms. In the world of viruses, many viruses use RNA as their genetic material, which can be used to divide viruses into DNA viruses and RNA viruses.

Microorganisms that cause human infectious diseases are mainly bacteria and viruses, which use DNA or RNA as their genetic material. Therefore, when detecting these microorganisms, people often use the general term "nucleic acid". The figure below lists the genetic material types of some well-known viruses.

Figure 1 Copyright image, no permission to reprint

2. Antigens: Enemies Recognized by the Immune System

All the components that are identified as "foreign invasion" or "non-self" by the immune system are antigens. Antigens are the "originators" that trigger immune responses. The word "original" means "the first, the beginning".

Under normal circumstances, when bacteria and viruses invade the human body, they will be recognized as antigens by the immune system, which will generate an immune response to eliminate the invaders. Sometimes the immune system cannot correctly identify and respond appropriately, and various problems will arise at this time. For example, low immune function leads to susceptibility to infection, excessive immune response leads to allergies, and even the immune system mistakenly recognizes its own normal components as antigens and reacts, leading to autoimmune diseases.

It can be seen that antigens can be any substance from outside the body or from the body, including "antibodies" produced by the immune system to resist antigens, and can also become "antigens" and be resisted by the immune system, producing "anti-antibodies". In reality, only those substances that can be recognized by the immune system and produce immune responses are qualified to be "antigens".

3. Antibodies: Trained Warriors of the Immune System

When antigens enter the human body, they stimulate the immune system to respond, one of which is to produce antibodies. This antibody only responds to the antigen that stimulates it, and does not respond to other antigens. The combination of antibodies and antigens is like a key accurately inserted into the corresponding keyhole. However, this combination itself cannot eliminate the invader. If the purpose of eliminating the invader is to be achieved, the antibody needs to "call for support" and summon other helpers to eliminate the invader.

Therefore, antibodies are substances produced by the human body itself that can target specific antigens. If a certain antibody, such as a specific antibody against the coronavirus, appears in the human body, it means that the coronavirus has or has invaded the human body.

There are different types of antibodies. During the infection process, the first type of antibody produced by the immune system is immunoglobulin M (IgM), because this type of antibody has superior capabilities and strong combat effectiveness, and is the "vanguard" in the antibody army. The next type of antibody produced is immunoglobulin G (IgG), which is the largest in number and is the well-deserved "main force" in the antibody army.

As the body recovers, the battle between antibodies and antigens ends, and the first antibodies to disappear are also IgM, while the level of IgG antibodies will gradually decrease or even disappear, but generally a certain level of IgG antibodies will be retained for a long time. Some antibodies, such as syphilis-specific antibodies, will persist for life.

4. What do negative or positive nucleic acid, antigen, and antibody mean?

1. Negative or positive results of nucleic acid test

This is a nucleic acid test report for the new coronavirus. When the result is negative, it is like the "virus battlefield" in the body has not found any traces of the "enemy" for the time being, or the "enemy" is too cunning and well hidden, and the number is lower than the standard that can be detected (300 copies/ml). Once the result is positive, it means that the "virus army" has invaded.

Figure 2 Copyright image, no permission to reprint

2. Negative or positive results of antigen test

Take influenza virus as an example. Antigen testing is like looking for "clues" left by influenza virus. If the test result is positive, it means that we have found influenza virus. The clinical significance of negative and positive antigen test is very similar to that of nucleic acid test, and there is good consistency between them.

3. Negative or positive results of antibody test

For example, when Mycoplasma pneumoniae invades the human body, the immune system responds and then produces antibodies against Mycoplasma pneumoniae. The first to appear is the IgM type, and a positive result means that the body is in the infection period or has recovered soon (because IgM will last for a period of time after recovery). Doctors need to combine symptoms, signs, epidemiological characteristics, etc. to comprehensively judge whether it is in the infection period.

A positive Mycoplasma pneumoniae antibody IgG test means that a Mycoplasma pneumoniae infection has occurred before, so it cannot be used for the diagnosis or auxiliary diagnosis of symptomatic Mycoplasma pneumoniae infection.

Although specific antibody IgG is rarely used to diagnose current infections, it also plays a big role in diagnosing past infections. The figure below briefly summarizes the clinical significance of the combination of specific antibody IgG and IgM tests for a certain pathogen.

Figure 3 Copyright image, no permission to reprint

V. Summary

In the diagnosis of infectious diseases, nucleic acid and antigen tests directly detect components of pathogens and are direct evidence of infection; while antibodies are specific substances produced by the human immune system against invading bacteria and viruses and are indirect evidence of infection.

Nucleic acid testing is usually the first to show abnormalities due to its high sensitivity, but its reporting timeliness is slightly poor. Antigen testing is convenient and the results are rapid, making it suitable for initial screening in outpatient clinics and emergency departments. Antibody testing has a certain lag, but plays a huge role in the diagnosis of non-respiratory diseases. The three methods have their own advantages and disadvantages. Doctors will combine the actual situation in diagnosis and treatment and choose the appropriate method for testing and diagnosis.