Inborn errors of immunity (IEI) are a diverse group of genetic conditions that impact the immune system’s ability to function correctly. Unlike contagious diseases, IEIs are inherited or occur spontaneously and are present from birth. These disorders are also known as primary immunodeficiencies (PID), a term still widely used interchangeably with IEI.
Understanding Inborn Errors of Immunity
IEIs stem from defects in specific genes, leading to a faulty immune system that cannot properly identify and fight off pathogens. This disruption can affect various components of the immune system, including antibodies, T cells, B cells, and complement proteins. The dysfunction caused by IEIs can manifest in several ways. Some individuals experience immunodeficiency, where the immune system is underactive, leading to frequent, severe, or unusual infections. In other cases, the immune system might be dysregulated, causing it to mistakenly attack healthy body tissues, resulting in autoimmune diseases or chronic inflammation. Over 485 different IEI types have been identified, each with a specific genetic cause, highlighting the complexity and heterogeneity of these conditions.
Recognizing the Signs
Individuals with IEI, particularly children, often experience recurrent, severe, or unusual infections that do not respond well to standard treatments. Examples include repeated episodes of pneumonia, ear infections, sinus infections, or deep skin abscesses. These infections might require intravenous antibiotics to resolve, indicating a compromised immune response.
Infants might show failure to thrive, meaning they do not gain weight or grow as expected. Autoimmune features, where the immune system attacks the body’s own tissues, can also be present, leading to symptoms like arthritis, skin rashes, or low blood cell counts. Unexplained inflammation, lymphoproliferation (enlarged lymph nodes or spleen), or certain malignancies can also be manifestations of an underlying IEI.
Diagnosis and Testing
Diagnosis typically begins with a healthcare provider’s suspicion based on a patient’s medical history and observed symptoms. A comprehensive review of recurrent infections, autoimmune conditions, inflammatory processes, and family history can guide the diagnostic pathway. Initial screening tests often include basic blood work, such as a complete blood count (CBC) to assess white blood cell levels, and immunoglobulin levels to measure antibody concentrations.
Following initial screenings, more specialized tests are employed to pinpoint the specific immune defect. Flow cytometry is a technique used to analyze different populations of immune cells, such as T cells and B cells, and assess their numbers and function. Genetic testing, including targeted gene sequencing panels, whole exome sequencing (WES), or whole genome sequencing (WGS, often with trio analysis of the patient and both parents), is increasingly used to identify the specific gene mutations responsible for the IEI. Early and accurate diagnosis is important for guiding treatment decisions and improving patient outcomes.
Treatment Approaches
Treatment for inborn errors of immunity is highly individualized, depending on the specific type of IEI and its manifestations. One common approach for individuals with antibody deficiencies is immunoglobulin replacement therapy (IgRT). This involves administering antibodies, usually intravenously or subcutaneously, to supplement the body’s missing or dysfunctional antibodies, helping to prevent infections.
For individuals prone to bacterial or viral infections, prophylactic antibiotics or antivirals may be prescribed to prevent recurrent illnesses. In some severe cases, hematopoietic stem cell transplantation (HSCT) may be considered. This procedure replaces the patient’s faulty immune cells with healthy cells from a donor, offering a potential cure. Emerging therapies also include targeted treatments like small molecule inhibitors or biologics that address specific immune dysregulation pathways, as well as gene therapy, which aims to correct the underlying genetic defects.
Living with the Condition
Living with an inborn error of immunity often involves ongoing medical care and specific lifestyle adjustments. Regular follow-up appointments with immunologists and other specialists are important to monitor the condition and adjust treatment as needed. Infection prevention strategies, such as meticulous hand hygiene and avoiding exposure to sick individuals, are routinely recommended.
Depending on the specific IEI, some live virus vaccines might be avoided, and immunization schedules may need careful consideration and monitoring of antibody responses. Patient advocacy groups and a multidisciplinary care team, often including immunologists, geneticists, and primary care physicians, play a supportive role in managing the condition. While challenges exist, advancements in diagnosis and treatment mean that many individuals with IEIs can lead full and productive lives with proper management. Approximately 70% of individuals with IEI can achieve a normal or near-normal quality of life with appropriate care.