X-linked Severe Combined Immunodeficiency (SCID): Pathogenesis & clinical findings
Abbreviations:
• Ig: Immunoglobulin
• IL: Interleukin
• NK: Natural Killer
• Th2: T helper 2 cell
• Treg: T regulatory cell
↓ IL-15 signaling ↓NK cell differentiation
and proliferation
↓ or absent NK cells in the blood, bone marrow and peripheral lymphoid tissues
Impaired innate immune system
Chronic Stress Response
Mutation of the IL2-RG gene encoding the interleukin receptor common gamma chain located on the X-chromosome
↓ IL-2 signaling ↓T cell
proliferation
Sequence analysis shows mutated, duplicated or deleted IL2-RG gene
↓ IL-7 signaling Global ↓ in
lymphocyte survival
Absent thymic shadow on X-ray
↑ susceptibility to fungal infections
Complete defect in cell mediated and humoral immunity
↓ antibody responses to vaccinations
↑ susceptibility to extracellular pathogens, most notably bacteria
Authors: Kyo Farrington Reviewers: Paul Adamiak Jessica Tjong Louis Girard* *MD at time of publication
↓ IL-4 signaling ↓Th2
differentiation
↓T cell help for B cell activation and class switching
Dysfunctional B cells
Genetic Predisposition
↓ Treg development
↑ risk of developing an autoimmune disease
↓ T cell response to mitogens or
anti-CD3 stimulation
↓ or absent T lymphocytes in the blood, bone marrow and peripheral lymphoid tissues
↑ susceptibility to viral infections (often gastrointestinal ones like rotavirus and/or enterovirus)
Chronic diarrhea
Hypoplastic lymphoid tissues (I.e. tonsils, adenoids, lymph nodes)
Hypermetabolic State
Failure to thrive
↓ antibody production in response to antigen exposure
↓ IgA, IgM and IgG serum concentrations
Note: IL2-RG gene encodes the interleukin receptor common gamma chain, which is a sub-unit common to the receptor complexes for IL-2, IL-4, IL-7, IL-9,
IL-15 and IL-21. The bolded/italicized cytokines contribute most to the pathophysiology of X-linked Severe Combine Immunodeficiency (SCID).
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Re-Published October 12, 2019 on www.thecalgaryguide.com