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Chapter 14: Immunology

Katie Kennedy; Juhee Lee; Soma Jyonouchi

APPROACH TO PRIMARY IMMUNODEFICIENCY

Clinical Red Flags for Immunodeficiency:

  • Frequent infections (respiratory, GI, or skin)

  • Severe or unusual infections

  • Unusual pathogen (Pneumocystis jirovecii, Burkholderia cepacia, Serratia marcescens, Aspergillus spp.)

  • Hospitalization for a common pathogen

    • ✓ Sepsis with an encapsulated organism (Streptococcus pneumoniae, Haemophilus influenzae)

    • ✓ Neisseria spp. infection

    • ✓ EBV or CMV

  • Persistence of a common pathogen that is usually cleared (Candida spp., HPV, molluscum)

  • Recurrent fevers without a source

  • Multisystem or early-onset autoimmunity

Recurrent urinary tract infections or streptococcal pharyngitis are not typically associated with immunodeficiency.

MAJOR CATEGORIES

Major categories of primary immune deficiencies reflect various parts of the immune system (Table 14-1).

Table 14-1Features and Diagnostic Approach for Primary Immunodeficiencies
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Table 14-1 Features and Diagnostic Approach for Primary Immunodeficiencies

Category

Select Conditions

General Features

Diagnostic approach

B-cell (antibody/humoral) disorders

  • X-linked agammaglobulinemia

  • Common variable immunodeficiency

  • Specific antibody deficiency

  • Transient hypogammaglobulinemia of infancy

  • IgA deficiency

  • Usually present after 3–6 months of age, after maternal antibodies decrease

  • Predisposition for infections of the upper and lower respiratory tract with encapsulated bacteria

Quantitative measures:

  • Serum immunoglobulin levels (IgG, IgA, IgM)

  • B-cell counts (CD19, CD20)

Functional measures:

  • IgG responses to vaccinations—Pneumococcus, tetanus, and diphtheria antibody titers

T-cell and combined (T- and B-cell) disorders

  • SCID

  • 22q11.2 deletion syndrome

  • Wiskott–Aldrich syndrome

  • Ataxia—telangiectasia

  • STAT3

  • DOCK8 deficiencies

  • Present at birth or in early infancy

  • FTT, chronic diarrhea

  • Prolonged and severe respiratory viral infections

  • Predisposition for fungal and opportunistic infections

  • Association with autoimmune diseases (ITP, hemolytic anemia)

Quantitative measures:

  • Absolute lymphocyte count on CBC with differential (80% of the ALC is comprised of T cells)

  • T cell counts (CD3, CD4, CD8)

  • TREC assay on SCID newborn screen

Functional measures:

  • Mitogen proliferation assay

Phagocyte disorders

  • Chronic granulomatous disease

  • Leukocyte adhesion deficiency

  • Severe congenital neutropenia

  • Present in early childhood

  • Predisposition to skin infections, pneumonia, lymphadenitis, and osteomyelitis

  • Poor wound healing, delayed separation of the umbilical cord, and omphalitis

Quantitative measures:

  • Absolute neutrophil count on CBC with differential

Functional measures:

  • Neutrophil oxidative burst (DHR assay)

Complement disorders

  • C1–C9 deficiencies

  • Extremely rare

  • Early complement component defects (C1, C4, C2): predisposition for lupus

  • C3 defects: predisposition for recurrent infections with encapsulated organisms

  • Terminal complement component defects (C5–C9): predisposition for recurrent meningococcal disease

  • CH50

  • AH50

  • Individual complement levels (if CH50 or AH50 abnormal)

Immune dysregulation disorders

  • IPEX syndrome

  • APECED

  • Polyendocrinopathies

  • Early-onset autoimmunity

  • Chronic diarrhea and/or FTT (IPEX)

  • Candidiasis (APECED)

  • FOXP3 gene sequencing (IPEX)

  • Autoimmune regulator gene sequencing (APECED)

APECED = autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy; CBC = complete blood count; FTT = failure to thrive; IPEX = immunodysregulation, polyendocrinopathy, enteropathy, X-linked; TREC = T-cell receptor excision circles.

HUMORAL IMMUNODEFICIENCIES: DIFFERENTIAL DIAGNOSIS

  • Immunoglobulin loss: Nephrotic syndrome or renal failure, severe burns, intestinal lymphangiectasia, chylous loss, severe enteropathy

  • Drug-induced: Antimalarial agents, captopril, carbamazepine, glucocorticoids, rituximab, phenytoin, sulfasalazine

  • Malignancy: Chronic ...

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