Page 546 - Clinical Immunology_ Principles and Practice ( PDFDrive )

524 Part four Immunological Deficiencies

TABLE 37.1 Infection Susceptibility of Select Primary Immunodeficiencies
Immunodeficiency Genetic Defect functional Defect Infection Susceptibility
Chronic granulomatous disease Gp91 phox , p22 phox , p40 phox , Defect in nicotinamide adenine Catalase positive bacteria (e.g.,
p47 phox , p67 phox dinucleotide phosphate (NADPH) Staphylococcus aureus, Burkholderia,
oxidase leading to abnormal serratia, Nocardia) and filamentous molds
superoxide production
Leukocyte adhesion disorder-1 β 2 integrin Neutrophil migration Bacteria, typically S. aureus, gram-negative
(LAD-1)
Severe congenital neutropenia HAX1, ELANE Neutropenia Bacteria, typically streptococci, S. aureus,
gram-negative
X-linked agammaglobulinemia Bruton tyrosine kinase (BTK) Absence of B cells, antibody Encapsulated bacteria, enterovirus,
production Helicobacter, and related species
CD40 ligand deficiency CD40 ligand Impaired B-cell class switching Encapsulated bacteria, Pneumocystis
jiroveci, Cryptosporidium
Severe combined Multiple genes, such as IL2RG, T-cell lymphopenia, variable B- and Bacteria, virus, P. jiroveci, Candida, Bacille
immunodeficiency (SCID) RAG1/2, ADA, JAK3, etc. natural killer (NK)-cell expression Calmette-Guérin (BCG)
DiGeorge syndrome Deletion of chromosome 22q11 Thymic hypoplasia or aplasia Viruses, opportunists infrequent
in majority
Autosomal dominant hyper-IgE Signal transducer and activator Impaired T-helper-17 (Th17) cell S. aureus, Candida, dimorphic fungi;
syndrome (Job’s syndrome; of transcription 3 (STAT3) differentiation secondary infection of pneumatoceles
AD-HIES) with molds, gram-negative bacteria and
nontuberculous mycobacteria
Dedicator of cytokinesis 8 DOCK8 T-cell lymphopenia, defect still S. aureus, Candida, Molluscum
(DOCK8) deficiency being delineated contagiosum, human papillomavirus
(HPV), herpes viruses
Interleukin-12 (IL-12)/interferon IFN-γR1, IFN-γR2, IL-12, IL-12R, Failure of signal transducer and Mycobacteria, Salmonella, dimorphic fungi
(IFN)-γ axis defects NEMO, STAT1 activator of transcription 1 (STAT1)
activation, intracellular killing
Complement C5–9 defects Specific complements Impaired membrane attack complex Neisseria species
killing

KEY CoNCEPtS
Infection Risks in Primary Immunodeficiencies

• Neutrophil defects present primarily with bacterial and fungal
infections.
• Humoral immunodeficiencies present with impaired antibody formation
and primarily sinopulmonary infections with encapsulated
organisms.
• Severe primarily T-cell defects usually present with opportunists, such
as Pneumocystis.
fIG 37.1 Chest computed tomography (CT) scan of a Nocardia • Abnormalities of the interleukin-12 (IL-12)/interferon (IFN)-γ axis com-
monly present with nontuberculous mycobacteria (NTM) infections.
pneumonia in a 17-year-old man with chronic granulomatous • Cytokine autoantibody syndromes are being increasingly recognized
disease. with infection susceptibility dependent on the involved cytokine.

warts are not infrequent. Fungal infections are unusual. Little is neutropenia. Benign ethnic neutropenia is seen primarily in
known about antimicrobial prophylaxis for LAD-1, but typically individuals of African descent and is usually asymptomatic.
prophylaxis with some coverage for oral flora, S. aureus, and Secondary causes of neutropenia also include antineutrophil
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GNB is provided, such as with amoxicillin/clavulanate. Other antibodies and hypersplenism with sequestration.
rare neutrophil defects, including Chediak-Higashi and Griscelli Infections associated with neutropenia relate to the etiology as
syndromes, also are characterized by recurrent pyogenic infections. well as the degree and duration of neutropenia. Cyclic neutropenia
may be largely asymptomatic, with self-limited fevers and oral
Quantitative Phagocyte Defects ulcers or cervical lymphadenopathy, as opposed to the severe
Neutropenia is the most common quantitative defect of phago- chronic neutropenia of infancy that has more serious infections.
cytes and typically results from cytotoxic agents, as discussed Neutropenia is most frequently associated with bacterial infections,
later in this chapter. Autosomal recessive defects in HAX1 cause often localized to the mouth, cervical lymph nodes, lungs, and
Kostmann syndrome, a type of severe congenital neutropenia, perianal area, with both gram-positive bacteria (GPB) and GNB.
which typically presents in infancy with recurrent bacterial Fungal infections are more frequent in the prolonged and severe
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infections. Autosomal dominant defects in the neutrophil elastase neutropenias associated with hematological malignancies and
gene ELANE cause severe congenital neutropenia and cyclic hematopoietic transplantation. Fever in the setting of neutropenia