What Are Primary Immunodeficiency Disorders?

The Immune System performs a highly-sensitive, highly-specialized and highly-coordinated set of activities. Any component that’s missing, malfunctioning or in short supply can have negative consequences.

Primary Immunodeficiency Disorders” (PID) is a class of disorders brought about by an absent, deficient or defective component of the immune system. These conditions, present at birth, are therefore considered “congenital immunodeficiencies.”

(PID is different from “secondary” immunodeficiencies like HIV-AIDS which are acquired during the lifetime.)

Babies with PID usually suffer from infections in the ears, skin, and lungs

Babies with PID usually suffer from infections in the ears, skin, and lungs

A baby born with the condition is said to be especially susceptible to infections from normally harmless pathogens. Recurrent infections, unusual in their severity, coupled with a prolonged time for recovery are signs of an immunological deficit. Babies with PID usually suffer from infections in the ears, skin, and lungs.   

A study looking into U.S. healthcare databases from 2001-2007 saw a significant increase in the prevalence of the diagnosis of PID. This increase may be partly attributed to the public’s growing awareness of the condition.

According to the National Center for Biotechnology Information, there are around 130 identified congenital immunodeficiencies or PID’s. Other medical organizations, such as the American Academy of Asthma, Allergy, and Immunology, peg this number as high as 300.

Causes & Symptoms

This type of weakened immune system is not caused by malnutrition, drugs, viruses or bacteria. And one can’t catch PID like a cold.

PID is genetic and hereditary in nature.

It may run in families when a parent passes a mutated gene to his or her offspring. A person with some form of PID may have family members or relatives who suffer from the same or similar condition. At times, genes would spontaneously mutate without any known or established triggers. The genetic anomaly then expresses itself in the abnormal development or functioning of certain elements of the immune system.

Because PID is present at birth, symptoms normally appear very early on in life—that is, several months after birth.

Clinical presentations would depend on the relevant immunological deficits. But generally, the unusual susceptibility to infections is a major bellwether.

According to the Jeffrey Modell Foundation (JMF), a leading organization for PID, signs of the condition include:

  • 8 or more ear infections within one year

  • 2 or more serious sinus infections in one year

  • 2 or more cases of pneumonia in one year

  • 2 or more deep-seated infections (like septicemia or meningitis)

  • 2 or more months of antibiotic treatment, with little or no improvement

  • Recurrent deep skin or organ abscesses (like in the lungs or liver)

  • Persistent fungal infection in the mouth or somewhere on the skin

  • The need for intravenous antibiotics to clear said infections.

  • Insufficient weight gain and growth of the baby

  • Family history of PID

If the baby has 2 or more of these symptoms, a specialized testing for PID is highly warranted.        

Classification of PIDS

The body has basically two types of immunity: Innate Immunity and Adaptive Immunity.

These two functions are performed by the different types of white blood cells (WBC’s or leukocytes)—blood components that are produced in the bone marrow, and that are either free-moving in the blood stream or stored in the lymph tissues.  

Innate Immunity

Innate immunity is the fast-acting, first line of defense that includes the WBC’s called phagocytes and macrophages. These are non-specific killer cells that simply neutralize foreign objects that enter the body. They work by engulfing bacteria and viruses. Once inside, these WBC’s destroy potential pathogens by releasing an acidic enzyme that “digests” the foreign entities.

The body’s innate immunity is perpetually primed to ward off any generalized threat.

It would be untenable to list all the various deficiency cases here, but some important illustrative examples include: 

Chronic Granulomatous Disease (CGD)

This is a condition where the patient’s immune system lacks the ability to form oxygen compounds that are necessary for fighting off certain pathogens. The most common form of the disease is said to be “X-linked,” that is, they often only affects boys.

Hyper-IgE Syndrome   

This is characterized by elevated levels of immunoglobulin E (IgE). The condition, whose clinical presentations include frequent bouts with pneumonia and eczema, is caused by a mutation in the gene (STAT3) that controls the production of the protein responsible for the maturation of the cells of the immune system.   

Interferon-γ and Interleukin-12 defect

This genetic condition is characterized by a susceptibility to tuberculosis and salmonella infections. The disease is basically a signaling problem, where the innate immune system fails to effectively communicate with an adaptive immune system. This results in the body’s inability to mount effective responses to specific viral and bacterial attacks. 

Treatment of Innate Immunity Disorders

There is considerable variation in the clinical presentations of the different disorders and therefore, the specifics of the treatment shall also vary accordingly. But in general, antibiotic therapy is used to treat the infection.   

Antibiotic prophylaxis and Antifungal prophylaxis can also be used. These are proactive and preventative approaches that keep patients from developing opportunistic infections.

Interferon-gamma therapy is a synthetic/manufactured substance that can stimulate the immune system as well as fight the viruses themselves. This can be given as a shot in the arm or thigh 3x a week and can be used to treat diseases like Chronic Granulomatous Disease (CGD)

Adaptive Immunity

The second type of immunity employs “immunological memory” in order to mount the most effective response. Persons that have been previously exposed to certain diseases are either immuned from future infections or have faster recovery time. It is said that their immune systems have “learned” to combat the disease. This type of acquired immunity is slower acting and more purposeful than innate immunity.

B-cells and T-cells are the mainstays of this form of immunity. B-cells work through the antibody-mediated pathway while T-cells are cell-mediated in nature.    

Again, the relevant deficiencies may be too many to individually enumerate, but illustrative examples include:

Wiskott-Aldrich Syndrome

This is a consequence of a mutation of the gene responsible for producing the protein that plays a major role in blood clots. The syndrome is characterized by low platelet count, petechiae, bruising and bloody diarrhea.

DiGeorge Syndrome

DiGeorge Syndrome is a deficiency in the number of T-cells in the body. This is caused by abnormal fetal development which leads to a small part of “Chromosome 22” missing. In addition to frequent infections, the syndrome’s clinical presentations include facial features like wide-set eyes, low-set ears and undeveloped chin.

Bruton’s Agammaglobulinemia

The disease is characterized by the absence of mature B-cells in the body, said to be caused by mutations of the BTK gene. The gene is responsible for the development and maturation of B-cells. Without healthy and functioning B-cells, the body is susceptible to a host of complications from streptococcus and enterovirus infections. 

Severe Combined Immune Deficiency (SCID)

This is considered to be one of the most serious PIDs where there is a combined absence of B-cells and T-cells in the body. It is also called the Bubble Boy disease, made famous by David Vetter in the 1970s.  He had to deal with the disease by living in sterile “bubble” conditions free from pathogens that may cause infections. 

Treatment of Adaptive Immunity Disorders

The specifics of the treatment will depend on the specific disorder being addressed. But in general, antibiotics, antibiotic prophylaxis, and antifungal prophylaxis are used. In cases of established infections, aggressive treatment may be employed.

Immunoglobulin replacement may also be ordered by a specialist. The antibodies will be infused intravenously through a “drip” session that lasts from 2-4 hours. Treatment may be needed every 3 weeks or so.

In some cases, a bone marrow transplant may be recommended. This is a procedure where a patient’s defective bone marrow is replaced with healthy bone marrow stem cells that can produce the necessary components that can fight off diseases and infections.     

Prognosis for PID

The long term outlook for persons with Primary Immunodeficiency Disorders will depend on the form and severity of the disease. Many have been able to lead normal and productive lives.

Early diagnosis is paramount so that supportive and definitive therapies can alleviate the condition as well as prevent further damage and complications. Because PID is congenital, babies have them at birth. Maternal immunoglobulin, the passive immunity passed down from mother to child, lasts only around 6-12 months. As this form of immunity wanes over time, the baby will be increasingly left to her own immune system for defense against infections. It is therefore vital to determine any immunological issue as early as possible.     

 

If your baby exhibits at least two of the symptoms of PID listed earlier, he or she might need to undergo specialized testing to ascertain his or her health condition. BloodWorks Lab provides you with the most reliable diagnostic tools, offering a range of immunological tests that help diagnose PID and other related diseases.

We are also proud to be the first laboratory in the Philippines to offer the Anti NMDA Receptor Antibody Test and the Anti Acetylcholine Receptor (lgG) Antibody Test.

BloodWorks Lab is your one-stop shop for all your blood test needs. Our branches are in Alabang and Katipunan.