Congenital Immunodeficiency
 Primary Immunodeficiency
Prevalence
 1 in 2000
Severe Cases
 Sx between 6 months and 2 years
Less Severe
 Sx present in Childhood
Warning Signs of Primary Immunodeficiency
 >4 New Ear Infections in One Year
 >2 Serious Sinus Infections in One Year
 >2 months of antibiotics with little
effect
 >2 Pneumonias within one year
 Failure of the infant to grow or gain
weight (failure to thrive)
 Recurrent, deep skin/organ abscesses
 Need for IV antibiotics to clear
infections
 > 2 Deep-Seated Infections
 Family History of Immunodeficiency
Combined Immunodeficiencies
Vaccines: Do NOT give LIVE Vaccines
GIVE: Pneumococcal, Hib
Adenosine Deaminase SCID
Cause
 ADA breaks down adenosine from food
for nucleic acid formation
o Deficiency can cause
pulmonary inflammation,
thymic cell death, defective T
cells
 Accumulation of Toxic Metabolites are
thought to cause SCID
Prone to: ADHD and Neurocognitive Impairment
Treatment:HSCT and Gene Therapy
 Enzyme Replacement Therapy-
ADAPEG
 ○
CD40L Deficiciency: Hyper IgM Type 1
Cause:
 X-Linked CD40L Deficiency
Presentation
 Low IgA, IgE, IgG; Hyper IgM
 Neutropenic
 Lack of Germinal Centers
Treatment
 Curative
 HSCT
 Supportive Care
 IVIG/SCIG
 Pneumocystitis Jiroveci
Pneumonia: Bactrim
 Granulocyte Colony
Stimulating Factor
Job’s Syndrome (Hyperglobulin E Recurrent
Infection Syndrome)
Prevalence: 1: 1,000,000
 Connective Tissue Disease
Organisms Related to Deficiencies
● Bacteria: Ab deficiency; combined deficiency;
phagocyte defect; complement deficiency
● Mycobacteria and Fungi: Combined Deficiency;
Phagocyte Defect
● Viruses: Antibody Deficiency; Combined
Deficiency
● Protozoa: Antibody Deficiency; Combined
Deficiency
Antimicrobial Prophylaxis
 Aggressive Treatment of Acute Infections
Gene Therapy
 Pedgemase Bovide ADA (ADAPEG)
Enzyme Replacement Therapy
IVIG/SCIG
● IVIG
○ Dosing: 400mg/kg IV q 3-4 weeks
○ Trough Goal: 500-1000 mg/dL
● SCIG
○ Dosing: 100mg/kg weekly → raises IgG Gradually
○ Reaches levels >500mg/dL after 3-4 weeks → Steady State after 6 months
○ Loading Dose: 100mg/kg daily x5 days → 5o0mg/dL is reached within one week
Severe Combined Immunodeficiency
Cause
● Genetic defects resulting in the
abnormal development of both B
and T cells
○ May also affect NK Cells
Prevalence: 1 in 58,000
Screening: T-Cell Receptor Excision Circle
(TREC)  Beta Actin Normal <25
Presentation:
 Diarrhea
 (Augmentin)
Recurrent Severe Infections
 Failure to Thrive
Categorization
 Categorized by the presence of NK
Cells
 Divided by Genetic Firms of
Patient
Phagocyte Deficiencies
 Give: Pneumococcal
AVOID: Live Vaccines
Clinical Presentation:
 Increased risk for infections
 Cold Absecesses, Eczema/Pruritic Dermatitis,
 Pneumonia
 STAT3 defect with pneumatoceles: may have
scoliosis >10 degrees
 DOCK8 without pneumatoceles: may have
neurologic symptoms and vasculitis
Hematopoietic Stem Cell Transplant Antibody Deficiencies: Introduction
 IV administration of usually allogenic stem cells (from matched) donor to restore cell IgG Characteristics
making function ● Infant IgG significantly increases after 3 months of age.
 5 year survival after HSCT: 70% ● Majority is Maternal IgG prior to 3 months of age
 90% of death occurs within the first two years Antibody Deficiency Characteristics
●
 Risk of Death: Disorders characterized by an inability to produce clinically effective immunoglobulin response
o Autoimmune Reactions ● Present with:
o Graft vs. Host Disease ○ Severe infections of the Ears, Respiratory Tract, Sinuses, and/or infection from Giardia spp.
o Poor Nutrition ● Diagnosis:
 Monitoring ○ Pts 30-40 years of age
o Immune System: Immune Globulin Counts, Cell Counts ○ Sometimes diagnosed younger
o Endocrine: TSH, Cortisol, GH ● Risks:
o Pulmonary: PFT, Spirometry ○ Higher risk for autoimmune disease (rheumatoid arthritis and IBD)
o Growth ○ Lymphoid and GI cancers
Concerns of IVIG Common Variable Immunodeficiency Bruton’s Agammaglobulinemia
● Sugar Content Prevalence Cause
○ Used as a stabilizer for aggregate ● 1 in 25,000 ● X-linked and Autosomal recessive defect
formulation prevention Cause in the Bruton Tyrosine Kinase Gene
○ No sugar in SC formulations ● Caused by a collection of genetic defects ○ This leads to the failure of B Cell
● IgA Content that impair B cell differentiation, which Development and Low IgG, IgM,
○ 0-720mcg/mL leads to primary IgA
■ Caution with patients hypogammaglobulinemia Sx
who are IgA deficient → Sx: ● 6-9 months of Age
Anaphylactic Reaction ● Recurrent Sinus and Middle Ear Infections ● Recurrent Sinopulmonary Infections
● Reduction in IgG (>2SD below the mean) ○ Failure to thrive
Treatment Ataxia-Telangiectasia and possibly a reduction in another Ig ○ Small or Absence of Lymph
Curative Treatment: Cause (IgA,IgE, IgM) Nodes/Tonsils
 HSCT, Gene Therapy, Enzyme Replacement  Autosomal Recessive Gene AT which is ● Failure to mount significant Ab response Treatment
Therapy found on chromosome 1122q.3 which after vaccination or natural infection ● NO curative therapy
Supportive Care results in defective DNA repair ● Some patients have normal Ab numbers, ● Supportive Care
 IVIG Detection but with impaired Ab function ○ IVIG/SCIG
Treatment ○ Antimicrobial Prophylaxis
 Antimicrobial Prophylaxis  Newborn Screening for TREC
● IVIG/SCIG ■ ~50% of patients
o Pneumocystitis Jiroveci (PJP): Reduction
● Antimicrobial Prophylaxis: ~50% of ■ Bactrim
Bactrim (Sulfamethoxazole-  Reduced T cells, IgA, IgG2, and other IgG
patients require (Sulfamethoxazole-
Trimetophrim) subclasses
○ Amoxicillin/Clavulanate Trimethoprim)
o Candida : Fluconazole Presentation
o Varicella, Cytomegalovirus: Acyclovir  Progressive neuronal loss (Atrophy of the
○ Amoxicillin
During RSV: Palivizumab Cerebellum)
○ Penicillin
 Ataxia, and eventually wheelchair bound
at 10-20 years of age
DiGeorge Syndrome Vaccines: Pneumoccoccal and Hib
 Patient is at a higher risk for cancer
Cause and Symptoms: CATCH22 Avoid: LIVE VACCINES
o 85% risk for Leukemia and
● Cardiac abnormalities (congenital heart
Lymphomas
Chediak Higashi Syndrome disease) Diagnosis
 Hypersensitive to ionizing
Cause ○ Most common: tetralogy of ● Dependent on the severity of the
radiation/chemotherapeutic options that
 Autosomal Recessive Variant in CHS1/LYST break DNA strands
Fallot, ventricular septal defect, diagnosis (Most Severe= BIRTH)
Gene pulmonary atresia ● Diagnosed by Fluorescent in-situ
 Hypoplastic thymus, lung disease, ocular
Prevalence ● Abnormal facial features: low set ears, hybridization analysis (FISH)
telangiectasia, malignancy
 <5oo cases small jaw, loss of bow-shaped lip Treatment
 Immunodeficiency presents with ●
Clinical Presentation Thymus abnormalities: higher risk for ● Symptom specific
sinopulmonary infections fungal and bacterial infections
 Partial Hypopigmentation of Skin, Iris, and Treatment
○ Hypocalcemia
Hair ● Cleft palate (delayed speech, feeding ■ Vitamin D and Calcium
 NO curative therapy issues)
 Pyogenic Infections of Skin, Urinary Tract ○ Cardiac Abnormalities
 Supportive Care ● Hypocalcemia/hypoparathyroidism ■ Surgery
and Mucous Membranes
o IVIG/SCIG ● 22 microdeletion (22q11.2) ○ Cleft Palate
Disease Accelerated by Epstein-Barr Virus
o Aggressive Antibiotic Therapy ■
Treatment Surgery
● Curative ○ Thymus Abnormalities
HSCT ■ Thymus Transplant
● Supportive Care ■ HSCT
○ Granulocyte-Colony Stimulating ●
Factor
○ Antimicrobial Prophylaxis
■ S. Aureus
● Sulfamethoxazole-
Trimethoprim
(Bactrim)
■ Fungal
● Itraconazole,
Voriconazole,
Posaconazole