Aileen Ancla Elorde, MD, MCHM, DPPS, DPSAAI

Child and Adult Allergy, Asthma, and Immunology

 Overview of the immune system
 Hallmarks of immunodeficiency
 Clinical manifestations of immunodeficiency
 Approach to diagnosis of immunodeficiency
 Management

 Specific immunodeficiencies
 B cell
 T Cell
 NK Cell
 Phagocytes
 Complement
 Immune system = organs, cells and molecules that
mediate resistance to infections

 Immune response = collective and coordinated

response to the introduction of foreign substances in
an individual mediated by the cells and molecules of
the immune system
 Defense against microbes

 Defense against the growth of tumor cells

 kills the growth of tumor cells

 Homeostasis
 destruction of abnormal or dead cells
(e.g. dead red or white blood cells, antigen-
antibody complex)
 adenoids
 Thymus
 Lymph nodes
 Spleen
 Peyer’s patches
 Lymphatic vessels
 Bone marrow
 Lymphocytes
 T-lymphocytes
 B-Lymphocytes, plasma cells
 natural killer lymphocytes
 Monocytes, Macrophage
 Granulocytes
 neutrophils
 eosinophils
 basophils
 Antibodies
 Complement
 Cytokines
 Interleukines
 Interferons
Progenitor

Progenitor
Two types of immunity:
Innate & Adaptive
Types of adaptive immunity
 Loss or inadequate function of various components
of the immune system

 Can occur in any part or state of the immune system

 physical barrier, phagocytes, B lymphocytes, T
lymphocytes, complement, natural killer cells

 The immuno-compromised host

 has an impaired function of immune system
 is at high risk for infection
 Congenital (primary) immunodeficiency
 genetic abnormality

 Acquired (secondary) immunodeficiency

 results from infections, nutritional deficiencies or
treatments
▪ AIDS, chronic leukemia
 1:10,000 live births
Notarangelo. JACI 2010

 Age and Sex

 Age of onset varies from syndrome to
syndrome
 40% - diagnosed on the first year of life
 40% - at 5 years
 15% - 16 years
 5% - adulthood
 Male/female ratio: 1.4:1 to 2:1

 family history of a similar deficiency:

25% of patients

 X-linked recessive, autosomal recessive,

autosomal dominant and sporadic
inheritance patterns are observed
E.R. Stiehm, Immunologic Disorders in Infants and
Children
Recurrent keeps coming back

Persistent won’t completely

clear up or clears up very slowly

Severe requires hospitalization

or intravenous antibiotics
 Absolute lymphocyte count

Lymphopenia : suggested if < 2000

cells / ml
present if < 1500 cells/ ml
Thus most patients most patients are asymptomatic in the first few months of life and begin to have recurrent infections between 4 and 12 m

IgG Antibody Levels

Anti Hepatitis B antibody titer
Cell Mediated Immunity Test:
Candida, Tetanus , PPD
High index of suspicion:
1. Recurrent infection despite adequate antimicrobial Tx
2. Infection with unusual or opportunistic organisms
3. Non response/poor response despite appropriate antimicrobial Tx

Detailed History and PE

Infections confined to a single organ system?

YES NO

LOCALIZED SYSTEMIC
 LOCALIZED SYSTEMIC

Consider: Identify presence of concurrent

conditions which
a. Anatomic/structural predispose to immune
abnormality (immotile deficiency
cilia: absence/poor quality
of secretions, obstruction:
structural defects)
PRIMARY SECONDARY
a. Chronic
irritation/inflammation on
site (e.g. allergic disease) 1. Treat underlying
disease
Identify specific defect 1. Find out specific
part of immune
system affected
 Identify specific defect
History
Identify pathogens (current and past)

Recurrent bacterial/pyogenic
infections

Staphylococcus; skin
abscess; Serratia,
Aspergillus

Suspect
phagocytic
defect
 Deep-seated abscesses due to Staphylococcus
aureus or mixed flora
 Skin infections (cold abscesses)
 High Absolute neutrophil count
 Delayed separation of umbilical cord
 Identify specific defect
History
Identify pathogens (current and past)

Recurrent bacterial/pyogenic
infections

Staphylococcus; skin Neisseria,

abscess; Serratia, Pneumococci;
Aspergillus H. flu, etc

Suspect Suspect
phagocytic complement
defect defect
 Recurrent pyogenic Meningococcal sepsis
infections and meningitis

 CH50 activity
 C3 level
 C4 level
 Identify specific defect
History
Identify pathogens (current and past)

Recurrent bacterial/pyogenic Recurrent fungal/viral/protozoal

infections mycobacterial infections

Staphylococcus; skin Neisseria,

abscess; Serratia, Pneumococci;
Aspergillus H. flu, etc

Suspect Suspect
phagocytic complement
defect defect

Suspect
T-cell defect
Mycobacterial infections

Severe viral infections

Candida or other fungal infections
No oral thrush

 CMI test is negative

 T cell enumeration is abnormal
 Identify specific defect
History
Identify pathogens (current and past)

Recurrent bacterial/pyogenic Recurrent fungal/viral/protozoal

infections mycobacterial infections

Staphylococcus; skin Neisseria,

abscess; Serratia, Pneumococci;
Aspergillus H. flu, etc

Suspect Suspect
phagocytic complement
defect defect
Other bacterial pathogens, esp
encapsulated; eg Haemophilus;
Suspect
Streptococcus; Pneumococcus; Gram (-) T-cell defect
Recurrent sinopulmonary infections
Low serum Immunoglobulin
Abnormal isohemagglutinins
 General
 Specific
 Comprehensive pediatric care
 Immunology
Clinic

Adolescent Pulmunology
Clinic Clinic

Genetics
PID GIN Clinic
Clinic

Infectious
Disease
ORL Clinic
Clinic
 Maintain general health and nutrition
 Prevent emotional problems
 Protect from unnecessary exposure to
infection
 Home treatment plan for those with chronic
pulmonary disease
 Precautions
 Blood products
▪ CMV negative and irradiated blood products

 Surgery

 Corticosteroids and immunosuppressive drugs

 Immunizations
 Avoid live vaccines in severe antibody and cellular
immunodeficiencies
▪ Vaccine-related polio infections – occurred in
immunodeficient patients
▪ BCG  disseminated infection

 Yearly influenza vaccine

 Recommended
 Also for family members
 Antibiotics
 Pneumocystis jirovecii prophylaxis
▪ T cell defects
▪ CD4 count : < 1500 (<12 months)
< 750 ( 12 – 23 months)
< 500 ( 2 to 5 years)
< 200 ( > 5 years old)
 Continuous antibiotics
 Prophylaxis : dental or surgical procedures

 Antivirals
 Human immunoglobulin
 The primary goal: prevent infections and to
minimize damage to the lungs (Bronchiectasis)

 Therapy should be started as soon as the diagnosis

is made

 Initial target therapy of 400-500 mg/kg every 3-4

weeks

 Target to keep trough IgG levels >800 mg/dl (some

studies suggest >1,000 mg/dL

Orange J, Clin of Immuno 2010

 Indicated for CVID, XLA, HIM, SCID, or functional
antibody deficient patients

 Anaphylactic infusion reactions can occur in the rare

patient who has IgE antibodies against IgA

 Gammagard and Polygam both contain trace

amounts of IgA, whereas others can have large
quantities of IgA
 Common
 Back and abdominal aches/pain
 Chills/fever
 Myalgias
 Headache

 Less common:
 Anaphylactic reaction
 Aseptic meningitis
 Renal dysfunction
 Live virus vaccines - diminished
immunogenicity when given shortly before or
during several months after receipt of IG

2006 Report of the Committee on Infectious

Diseases
 Plasma
 Leucocyte transfusions – phagocytic defects
 Enzyme replacement – Adenine deaminase
 Cytokines – interferon gamma in CGD
 Stem cell transplants
 HLA-matched related marrow grafts are the
treatment of choice for all variants of SCID;
 however, 75% to 80% of patients lack such a donor

 Transplantation of HLA haplotype–disparate

parental marrow depleted of T cells by using
soybean agglutinin/sheep red blood cells
Gene therapy

 polyethylene glycol adenosine deaminase

(PEG-ADA) enzyme replacement therapy

for the treatment of adenosine deaminase

(ADA)–deficient SCID

JACI 2008.
 requires prior identification of the disease-causing
mutation in the family

 carriers usually do not develop clinical findings related to

the disorder
 Newborn Screening Program for Severe
Combined Immunodeficiency (SCID) by T-
Cell Receptor Excision Circles (TRECs)

 TRECs - present in naïve T cells

 use of real time PCR quantitate the number of TRECS in DNA

extracted from punches of dried blood spots on newborn
screening cards
JACI .
February2009
 Overview of the immune system
 Definition of Primary Immunodeficiency (PID)
 Warnings signs of PID
 Diagnosis
 Management
 Prognosis
 Summary
 Cellular and combined PID : poorest
prognosis
 Chronic tissue damage may not be prevented