From the Guidelines
Diagnosis of immunodeficiency disorders requires a systematic approach beginning with a thorough clinical evaluation followed by appropriate laboratory testing. The initial assessment should include a detailed medical history focusing on recurrent infections, their frequency, severity, and causative organisms, as well as family history of immunodeficiencies 1. Physical examination should look for signs of chronic infections, lymphoid tissue abnormalities, and characteristic features of specific syndromes. Laboratory testing typically follows a tiered approach, starting with complete blood count with differential to assess for neutropenia, lymphopenia, or other cytopenias. Immunoglobulin levels (IgG, IgA, IgM, IgE) should be measured to identify antibody deficiencies, along with specific antibody responses to vaccines. Lymphocyte subset analysis by flow cytometry helps quantify T cells, B cells, and NK cells. Functional immune testing may include lymphocyte proliferation assays, neutrophil function tests, and complement pathway evaluation. For suspected primary immunodeficiencies, genetic testing is increasingly important, with next-generation sequencing panels or whole exome/genome sequencing helping identify specific mutations 1.
Some key points to consider in the diagnostic criteria for immunodeficiency disorders include:
- Recurrent infections, particularly those caused by opportunistic pathogens or those that are severe, persistent, or recurrent
- Family history of immunodeficiency or early death from infection
- Failure to thrive or growth retardation
- Autoimmune or inflammatory disorders
- Malignancy, particularly lymphoma or other hematologic cancers
The diagnostic approach should be tailored to the individual patient's presentation and may involve a combination of laboratory tests, including:
- Complete blood count with differential
- Immunoglobulin levels (IgG, IgA, IgM, IgE)
- Lymphocyte subset analysis by flow cytometry
- Functional immune testing (lymphocyte proliferation assays, neutrophil function tests, complement pathway evaluation)
- Genetic testing (next-generation sequencing panels or whole exome/genome sequencing)
A definitive diagnosis is crucial for implementing appropriate treatment strategies and preventing complications, and often requires collaboration between immunologists, infectious disease specialists, and geneticists to interpret complex results and establish a definitive diagnosis 1.
From the Research
Diagnostic Criteria for Immunodeficiency (ID) Disorders
The diagnostic criteria for Immunodeficiency (ID) disorders involve a combination of clinical evaluation, laboratory tests, and genetic testing. The following are some of the key diagnostic criteria:
- A careful history to delineate the pattern of infectious organisms and other complications is important to guide the workup of these patients 2
- Initial workup of suspected immune deficiencies should include:
- Complete blood counts
- Serologic tests of immunoglobulin levels
- Vaccine titers
- Complement levels 2
- Laboratory evaluation involves quantitative and functional classic testing, such as:
- Leukocyte counts
- Serum immunoglobulin levels
- Specific antibody titers in response to vaccines
- Enumeration of lymphocyte subsets 3
- Genetic testing, including individual gene evaluation via Sanger sequencing or unbiased evaluation based on next-generation sequencing, is also essential for diagnosing primary immunodeficiency disorders 3
- Advanced research techniques, such as flow cytometric-based assays, may be necessary to validate genetic or other findings 2
- Screening tests, including clinical chemistry, bacteriological, serological, and radiological investigations, and skin tests with recall antigens, can help detect primary B cell defects with humoral antibody deficiency syndromes 4
Laboratory Tests for Evaluating the Immune System
Laboratory tests for evaluating the immune system in patients with primary immunodeficiency disorders include:
- Lymphocyte subset counts
- Immunoelectrophoresis
- Bone marrow biopsy
- IgG subclass defects
- Granulocyte dysfunction and complement defects 4
- T cell function tests 4
- Flow cytometric-based assays to test immune cell function, intracellular cytokine production, cellular signaling pathways, and protein expression 2
Importance of Early Diagnosis
Early diagnosis is essential for referral to specialized care centers and the prompt initiation of appropriate therapy 5. Timely diagnosis can improve outcome and reduce morbidity and mortality in primary immunodeficiency diseases 6.