Resources
Articles / Journals
Niaid.nih.gov
Webmd.com
Mayoclinic.org
Aaaai.org
Primaryimmune.org
Medicinenet.com
Piduk.org
Gallo, Vera, Laura Dotta, Giuliana Giardino, Emilia Cirillo, Vassilios Lougaris, Roberta D’Assante, Alberto Prandini et al. “Diagnostics of primary immunodeficiencies through next-generation sequencing.”
Frontiers in immunology 7 (2016): 466.
Clinical Updates
Jindal, Ankur Kumar, Rakesh Kumar Pilania, Amit Rawat, and Surjit Singh. “Primary immunodeficiency Disorders in india—A situational review.”
Frontiers in immunology 8 (2017): 714.
Videos
What are Primary Immune Deficiencies?
Primary Immune Deficiencies (PID) or Primary Immune Disorders are a group of rare, genetic disorders (with more than 350 types) which cause dysfunction in the immune system. With a dysfunctional immune system, children and adults with PID are exposed to chronic, life-threatening infections in the respiratory system, ears, eyes, skin, lymphatic system, joints, spinal cord and other internal organs. Depending on the severity, PID is usually diagnosed in infancy, early childhood or adulthood. In some cases, PID can be fatal if the infection is left untreated.
- PIDs are classified into six groups based on the part of the immune system affected:
- B cell (antibody) deficiencies
- T cell deficiencies
- Combination B and T cell deficiencies
- Defective phagocytes
- Complement deficiencies
- Unknown (idiopathic)
- Wiscott-Aldrich Syndrome
- Severe Combined Immunodeficiency Disease (SCID)
- DiGeorge Syndrome
- Ataxia-telangectasia
- Chronic Granulomatous Disease
- Transient Hypogammaglobulinemia Of Infancy
- Agammaglobulinemia
- Complement Deficiencies
- Selective Iga Deficiency
- Isolated Igg2 Subclass Deficiency
- Transient Hypogammaglobulinemia Of Infancy
- Familial Hemophagocytic Lymphohistiocytosis (Hlh)
- Autoimmune Lymphoproliferative Syndrome
- Neutropenia
- Leukocyte Adhesion Defect (Lad)
- Disorders of IFNγ-IL12 Pathway
- X-Linked Agammaglobulinemia (XLA)
- Wiskott-Aldrich Syndrome
- Severe Combined Immune Deficiency (SCID) caused by mutations in the common gamma chain
- Hyper IgM Syndrome caused by mutations in CD40 ligand
- X-Linked Lymphoproliferative Disease
- Chronic Granulomatous Disease (CGD)
- Severe Combined Immune Deficiency
- Chronic Granulomatous Disease
- Ataxia-Telangiectasia
- Some of the PIDs can be inherited in an autosomal dominant pattern (50% chance of each child inheriting the disease) where one parent has the disorder:
- Hyper IgE Syndrome caused by mutations in STAT3 (Jobs syndrome)
- Hypogammaglobulinemia
- DiGeorge Syndrome
An infant who is born with PID is likely to develop symptoms within a few months. Many babies present with common cold which turns into more severe bronchitis or pneumonia. Some of the signs and symptoms of PIDs include:
- four or more infections in a year in the eyes, ears, lungs, skin, mouth and genitals
- infections do not clear up without IV antibiotics
- severe infections like septicemia and other bacterial infections
- chronic thrush in the mouth and throat
- frequent bouts of pneumonia
- blood tests – to check for normal levels of infection fighting protein (immunoglobulins). Blood tests can also check if the body is producing antibodies which kill bacteria and viruses
- next-generation sequencing (NGS) and whole exome sequencing (WES) is used when PID is difficult to diagnose because of complex and atypical symptoms
- Immunoglobulin therapy comprises antibody proteins required for the immune system to fight infections. Usually this is in the form of an IV drip and needs to be given every 2-3 weeks
- Gamma interferon therapy is used to treat chronic granulomatous disease. This is a substance which can fight viruses and stimulate immune system cells. This can be given as an intramuscular injection three times a week
- Growth factors are used when the immune system lacks white blood cells. Stimulating the production can help prevent and fight infections
Gene therapy has the potential for a permanent cure for PIDs.Gene therapy research for the PIDs began as early as 1990. In gene therapy, the defective genes causing PID are replaced with healthy genes using a vector for delivery. The patient’s stem cells are extracted and the same corrected cells are infused back into the patient. Some form of conditioning with chemotherapy may be required prior to the procedure. The biggest advantage of gene therapy is there is no chance of rejection like in the case of bone marrow/stem cell transplant.
Some of the gene therapy trials for PIDs have cured around 20 children with X-linked severe combined immunodeficiency (X-SCID). In 2000, 14 patients with X-linked chronic granulomatous disease (CGD) underwent gene therapy in centres in the US, Europe and Korea. Currently gene therapy trials for Wiskott–Aldrich syndrome (WAS), X-linked lymphoproliferative disorder (XLP) and two forms of hemophagocytic lymphohistiocytosis (HLH) are in the research phase.
Children and adults with PID can participate in all life activities and must be encouraged to go to regular schools, colleges and participate in social activities. Genetic counselling and psychosocial counselling must be made available whenever required with other supportive measures. While one needs to be careful and avoid unnecessary infections, it does not mean that individuals cannot participate in most life activities.
Individuals with PID must maintain good hygiene at all times by regular bathing and washing of hands with soap and water. A healthy, balanced diet, physical activity, sufficient sleep and avoiding stress can prevent unnecessary infections. All individuals with PID must check with their doctor before taking any vaccinations.
If there is a known case of PID in the family, it is absolutely essential for closest relatives like siblings, uncles, aunts and cousins to test for carrier status.
If a woman with a carrier status is pregnant, prenatal test is essential to determine if the fetus has the disease mutation.