A: Severe combined immunodeficiencies (SCID)
Definition
Combined immunodeficiency syndromes are a heterogeneous group of disorders arising from a disturbance in the development and function of both T and B cells (cellular and humoral immunity) and may also involve natural killer (NK) cells. Combined immunodeficiencies are termed “severe” when they lead to early death from overwhelming infection, typically in the first year of life. Severe combined immunodeficiency (SCID) can be categorized as typical SCID or, if less severe, leaky SCID based upon the severity of T cell qualitative and quantitative deficiency.
B: Combined Immunodeficiencies (CID)
Definition
Several genetic mutations lead to variable immune defects of humoral and cell-mediated immunity. Combined immunodeficiency syndromes are somewhat arbitrarily distinguished from severe combined immunodeficiency (SCID) in that they do not characteristically lead to death from overwhelming infection in the first year of life. The most frequent forms of CIDs are associated with genetic defects in development of T and/or B lymphocytes. These defects are classified according to presence or absence T, B and natural killer cells (NK cells)
Panel test
1. CD4+ T cell Recent Thymic Emigrants (RTEs)
2. Lymphocyte subset
Test enumerates the percent and absolute cell count of lymphocyte subsets in whole blood for:
CD3 (total T cells)
CD4 (helper T cells)
CD45RA (naive helper T cells)
CD45RO (memory helper T cells)
CD8 (cytotoxic T cells)
CD4:CD8 ratio
CD19 (B cells)
Natural killer (NK) cells
3. Natural Killer Cell and Natural Killer T cell subset
Pct CD3-CD16-/+CD56br/dim (total NK cells)
Abs CD3-CD16-/+CD56br/dim (total NK cells)
Pct CD3-CD16+CD56dim (cytotoxic NK cells)
Abs CD3-CD16+CD56dim (cytotoxic NK cells)
Pct CD3-CD16-CD56br (cyto secreting NK)
Abs CD3-CD16-CD56br (cyto secreting NK)
Pct CD3-CD57+ (CD57 NK cells)
Abs CD3-CD57+ (CD57 NK cells)
Pct CD3+CD56+ (CD56 NKT cells)
Abs CD3+CD56+ (CD56 NKT cells)
Pct CD3+CD57+ (CD57 NKT cells)
Abs CD3+CD57+ (CD57 NKT cells)
Pct CD45+CD3+ (T cells)
Abs CD45+CD3+ (T cells)
Pct CD45+CD3- (Non T cells)
Abs CD45+CD3- (Non T cells)
Natural killer T-cell panel interpretation
4. B cell memory and Naïve
Measures B cells (CD19+)
Total memory B cells (CD19+/CD27+)
Class-switched memory B cells (CD19+/CD27+/IgD-)
Nonswitched/marginal-zone memory B cells (CD19+/CD27+/IgD+)
Naive B cells (CD19+/CD27-/IgD+)
5. Quantitative Immunoglobulins (IgA, IgG, IgM)
6. Toll like receptor function
7. Lymphocyte Antigen, Mitogen, anti CD3, anti CD28 and IL-2 Proliferation
References
Guidelines
- Picard C, Gaspar B, Al-Herz W, Bousfiha A, Casanova J, Chatila T, Crow YJ, Cunningham-Rundles C, Etzioni A, Franco JL, Holland SM, Klein C, Morio T, Ochs HD, Oksenhendler E, Puck J, Tang ML, Tangye SG, Torgerson TR, Sullivan KE. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. J Clin Immunol. 2018; 38(1): 96-128. PubMed
- Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, Keller M, Kobrynski LJ, Komarow HD, Mazer B, Nelson RP, Orange JS, Routes JM, Shearer WT, Sorensen RU, Verbsky JW, Bernstein DI, Blessing-Moore J, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph CR, Schuller D, Spector SL, Tilles S, Wallace D, Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the Joint Council of Allergy, Asthma & Immunology. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015; 136(5): 1186-205.e1-78. PubMed
- Diagnostic & Clinical Care Guidelines for Primary Immunodeficiencies. Immune Deficiency Foundation. Towson, MD [Accessed: Dec 2017]
- IDF SCID Newborn Screening Campaign. Immune Deficiency Foundation. Towson, MD [Accessed: Dec 2017]
C: Predominantly Antibody deficiencies:
a) hypogammaglobulinemia
Definition
Hypogammaglobinemia is a primary immunodeficiency disease (PID), characterized by an early blockage of B-cell development in the bone marrow, resulting in a low or absence of serum antibodies and low or absence of circulating B cells (1).
b) other antibody deficiencies
AID deficiency
UNG deficiency
INO80
MSH6
Selective IgA deficiency
Transient hypogammaglobulinemia of infancy
IgG subclass deficiency with IgA deficiency
Isolated IgG subclass deficiency
Specific antibody deficiency with normal Ig levels and normal cells
Ig heavy chain mutations and deletions
Kappa chain deficiency
CARD11 GOF
Panel tests
1 serum quantitative IgA, IgG, and IgM
2 Immunoglobulin G Subclasses (1, 2, 3, 4)
3 B-Cell Memory and Naive Panel
· Measures B cells (CD19+)
· Total memory B cells (CD19+/CD27+)
· Class-switched memory B cells (CD19+/CD27+/IgD-)
· Nonswitched/marginal-zone memory B cells (CD19+/CD27+/IgD+)
· Naive B cells (CD19+/CD27-/IgD+)
4 Lymphocyte Subset Panel
percentage and absolute counts for:
· CD2, CD3 (total T cells)
· HLA-DR, CD4 (helper T cells)
· CD45RA (naive helper T cells)
· CD45RO (memory helper T cells)
· CD8 (cytotoxic T cells)
· CD19 (B cells)
· NK cells
· CD4:CD8 ratio
5 Lymphocyte Antigen and Mitogen Proliferation Panel with Cytokine Response
References
Guidelines
- Diagnostic & Clinical Care Guidelines for Primary Immunodeficiencies. Immune Deficiency Foundation. Towson, MD [Accessed: Dec 2017]
- Picard C, Gaspar B, Al-Herz W, Bousfiha A, Casanova J, Chatila T, Crow YJ, Cunningham-Rundles C, Etzioni A, Franco JL, Holland SM, Klein C, Morio T, Ochs HD, Oksenhendler E, Puck J, Tang ML, Tangye SG, Torgerson TR, Sullivan KE. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. J Clin Immunol. 2018; 38(1): 96-128. PubMed
- Bousfiha A, Jeddane L, Picard C, et al. The 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies. J Clin Immunol 2018; 38:129.
