Inherited Immune Disorders, also called Primary Immunodeficiencies (PI), include more than 450 rare diseases where the body’s immune system is either missing vital parts or does not work properly due to genetic flaws. These conditions are present from birth, not acquired later, and result in the body having a reduced ability to fight off infections. 

Some conditions that may be more familiar to people are Common Variable Immune Deficiency (CVID), Bubble Boy Syndrome or Severe Combined Immunodeficiency (SCID), and Hyper IgM.  

What causes PI? 

Click image to open a larger version in a separate window

The genetic flaws that lead to various forms of PI cause one or more problems in the functioning of the immune system. We inherit our immune system from our biological parents (half from each parent) and the system has two parts: the innate immune system that prevents infections from the time we are born, and the adaptive immune system that learns about pathogens as they are encountered during our lives and adapts to fight them. Different parts of the immune system are affected depending on the specific condition. 

People can be born with a malfunctioning immune system in three ways. “Autosomal” refers to any of the 22 non-sex-related genes, while "X-linked" refers to genetic conditions determined by the X chromosome. There are no primary immunodeficiencies linked to the Y chromosome. Genetic screening before attempting pregnancy can help couples identify any risks.

• Autosomal Dominant: A person of either sex inherits an autosomal dominant gene where a single copy of the gene from one parent results in disease. 
• Autosomal Recessive: A person of either sex inherits two autosomal recessive genes, one from each parent, that results in disease. In this case, two copies of the gene are required for the disease to affect the child. 
• X-linked Recessive: A male child inherits one copy of an X-linked recessive gene from a parent that results in disease. Because two copies of the recessive gene are needed to cause illness in female children, it is extremely rare for girls to be affected by X-linked recessive conditions.  

How does PI affect people? 

PI may affect a single part of the immune system, or multiple components, and there is a wide range of symptoms. Some diseases are life-threatening, while others are mild. People with a mild PI may not even realize it, while a severe PI can reduce life expectancy or require continuous, lifelong medical care. 

Infections due to PI can occur in many parts of the body – skin, ears, nose and throat, sinuses, internal organs or intestinal tract, brain or spinal cord, or other areas. When infections occur, they are difficult to clear up and may recur or become severe, or may be caused by organisms that do not normally make people ill. 

The immune system protects the body from cancer, so those with PI are more susceptible to having certain cancers, such as lymphoma and breast cancer. 

PI can be diagnosed through laboratory testing, genetic testing, and routine screening of newborns. 

Why is a blood stem cell or bone marrow transplant a possible cure for PI? 

Because many functions of the immune system begin in the bone marrow, where blood cells and immune cells (like white blood cells, B cells, and natural killer cells) are produced, replacing diseased bone marrow with healthy hematopoietic stem cells from a donor can generate a new immune system that functions normally. A donor’s hematopoietic stem cells can be collected from either the circulating blood or the bone marrow. 

A successful transplant relies on the donor and recipient having a matching immune system. About 30% of patients can find a donor within their family, while 70% of patients must rely on marrow registries to search for an unrelated match.  

Matching factors are inherited, similar to the way we inherit hair and eye color from our parents and ancestors, so the best chance of a match is with someone of similar ethnicity or genetic heritage. Those of minority ancestry face more difficulty in finding donors due to lower representation in the worldwide registry. Minority donors are urgently needed to join the registry and help save lives. 

What can I do to help? 

If you are 18 to 35 and in general good health, please join the registry. Click here to order a swab kit sent to your home. Follow the instructions to complete the kit and return it to Gift of Life in the prepaid envelope. Your swabs will be tissue typed and your profile added to the worldwide registry with an anonymous ID number. Your privacy is protected the same as when you visit your doctor.  Those 36 to 60 may join the registry for a $60 processing fee; this allows us to focus our financial resources on the 18 to 35 demographic who are most likely to be asked to donate.   

We encourage you to hold a recruitment drive at your school or college, synagogue or church, or community event. Gift of Life will provide you with the training, supplies, and marketing materials to get started. Learn more about how you can run a drive.   

Gift of Life is also seeking volunteers to help us at fundraising events, making educational presentations, at recruitment tables, at our annual 5k run and walk, and in our office.  Learn more about volunteering with Gift of Life, just complete the form and someone will reach out to you.    

Sources 

•    https://primaryimmune.org/ 
•    https://www.niaid.nih.gov/diseases-conditions/types-pidds
•    https://www.cdc.gov/genomics/disease/primary_immunodeficiency.htm
•    https://hyperigm.org/ 
•    https://immunodeficiency.ca/primary-immunodeficiency/primary-immunodeficiency-pi/ 
•    https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/x-linked-recessive-inheritance