An immune system gone wrong, the new era of inborn errors of Immunity.

Patients presenting with an increased susceptibility to infections, autoimmunity, autoinflammation, severe allergies or malignancy may suffer from inborn errors of immunity (IEI). These are the five major manifestations of IEI, some of which may be present simultaneously or follow in no specific order. Inborn errors of immunity are a heterogeneous group of disorders that may affect the development, quantity and quality (function) of cells of the immune system. A total of 485 IEI have been described and the clinical presentation is highly variable. Inborn errors of immunity are estimated to occur in one in 1 000 to one in 5 000 individuals. Many of these patients present at their primary health care provider, and general practitioners need to familiarise themselves with some of the most common diagnoses. The early diagnosis and management of a patient with an IEI is critical to avoid life-threatening complications, preserve organ function, improve quality of life and reduce healthcare costs. Inborn errors of immunity may present at any age. Their accurate and timely diagnosis requires a high index of suspicion and appropriate laboratory evaluation.

Case study: Coeliac disease and IGA deficiency.

Coeliac disease is an immune mediated multisystem inflammatory disorder triggered by the consumption of gluten (found in wheat, rye and barley) in genetically predisposed people. Coeliac disease affects people of all ages, but is more commonly seen in females. The genetic predisposition is well established to be in the HLA gene – HLA DQ2 and HLA DQ8.5 Most adults (>95%) will present with non-classical symptoms and the diagnosis is often delayed (refer to Table 1). A histological assessment of the small bowel is almost always necessary to evaluate the degree of villous atrophy and inflammatory infiltration .

Component-resolved allergy diagnostics.

Allergic disease is a common condition worldwide, but unfortunately diagnosing the offending allergen is not always straightforward. An allergy is a hypersensitivity reaction initiated by the immune system. Allergic reactions could be IgE (antibody)- or non-IgE-mediated (cell-mediated). Refer to Table 1 for more information. Reactions not initiated by the immune system are not classified as an allergy, and cannot be detected by allergy tests, e.g. lactose intolerance, sensitivity to caffeine and other food intolerances such as to gluten.

Case illustration: Metal allergy

The incidence of metal hypersensitivity in the general population is on the rise, likely attributed to chronic low-level environmental exposure and an increase in joint replacement surgeries. Allergic reactions to the metals used in joint replacement prosthetics fall under type IV (delayed or cell-mediated) hypersensitivity reactions. These reactions occur when metal ions form complexes with endogenous proteins, acting as allergens that trigger activation and the proliferation of memory T lymphocytes. The symptoms of type IV hypersensitivity can manifest within days or even weeks after surgery.  

A critical approach to systemic connective tissue diseases

The systemic connective tissue diseases (CTD) include conditions such as rheumatoid arthritis, systemic lupus erythematosus (SLE), systemic sclerosis, Sjögren syndrome, polymyositis, dermatomyositis, ANCAassociated vasculitis, mixed connective tissue disease (MCTD) and undifferentiated connective tissue disease. Autoantibodies are a hallmark finding. Their analysis is an essential part of classification, diagnosis and monitoring of CTDs. The clinical assessment guides diagnostic testing for specific autoantibodies and a sound knowledge of the diagnostic criteria is required to formulate a differential diagnosis.

Autoimmunity in the nervous system

Autoimmune disorders of the nervous system have become more frequently suspected in the differential diagnosis of neurological disease. This is largely due to greater understanding of the underlying pathogenesis, underscored by the ever-evolving discoveries of targeted autoantigens. This has revolutionised the laboratory work-up of patients suspected of having autoimmune-mediated neurological disease.


Health Professions Council of South Africa


3 Clinical


Attempts allowed: 2

70% pass rate


For any additional information please visit the AMPATH Website

Enquire Now

Ampath Laboratories DxINSIGHTS - Issue 5 - November 2023