Specific antibody deficiency

Specific Antibody
Deficiency
Jintana Chataroopwijit
28 April 2017

Outline
 Introduction
 Pathophysiology
 Epidemiology
 Natural history
 Clinical manifestation
 Diagnostic evaluation
 Management
 Prognosis

Introduction
 Impaired polysaccharide responsiveness (IPR)
 Selective polysaccharide antibody deficiency
 Definition
 failure of response to polysaccharide antigens
 setting of recurrent infection
 normal immunoglobulin isotype
 normal serologic response to protein antigens
 age : ≥ 2 years old
Journal of Immunotoxicology 2008
Practice Parameter 2015
Immunology Allergy Clinical North America 2015

Pathophysiology
 No single immunologic mechanism
 Delayed physiologic maturation of
immune system

Immunodeficiency associated
with impaired vaccine response

Epidemiology
 Not well establish in general population
 In 2006, 15% of children with recurrent infection
 In UK 2012, 58% of children with chronic cough
 In 2011, 12% in adult with refractory chronic
rhinosinusitis

 Symptoms and immunologic finding may improve with
age
 50% resolution within 3 years
 Permanent sequelae or organ damage secondary to
infection : rare
 In adult
 Attention to permanent sequelae and organ damage
 Progression to severe form of PIDD
Natural History

Clinical manifestation
 Similar to antibody deficiency syndrome
 Chronic and recurrent otitis media, sinusitis, bronchitis,
pneumonia
 More frequent, severe, prolonged than normal host
 Pattern : partial or temporary improvement with
antibiotic therapy but rapid return of infection on
discontinuation of antibiotic  need antibiotic
prophylaxis

 In USA, relatively absence of life-
threatening infection
 Not appropriately identified and treated 
bronchiectasis or severe refractory sinusitis

 Pattern of otitis media in SAD
 Early onset of infection : 3-4 months of age
 Recurrence of infection of antibiotic treatment
 Recurrence after tympanostomy tube placement
 Need for replacement of tympanostomy tubes
multiple times
 Other atopic disease
 55% rhinitis
 58% asthma

Clue for suspected antibody defect in
patient with presumed allergic
rhinosinusitis/asthma

Diagnosis Evaluation
 Detailed history
 Physical examination
 Focused on
 Pattern of infection
 Documentation of pathogens previously isolated
 Consideration if any permanent sequelae

Diagnosis Evaluation
 Laboratory investigation
 Complete blood count with differential
 Immunoglobulin isotypes
 Baseline pneumococcal serotype-specific IgG antibody
titers
 Optional : immunization with PPV23

Laboratory considerations regarding
antipneumococcal antibody titers
 Young children : completion of PCV13 before
challenge with PPV23 is recommended
 Evaluation of PPV23 response : Measurement of
PPV23-exclusive serotypes

Serotypes
contained
in
pneumo
coccal
vaccine

 IgG serotype-specific antipnuemococcal
antibody assessment
 Standard method : ELISA
 Developing method : using Luminex
Laboratory considerations regarding
antipneumococcal antibody titers

 > 0.35 microgram/milliter
 against invasive infection
 > 1.3 microgram/milliter
 against mucosal infections
 threshold response to PPV23
Protective level of serotype-specific titers

Interpretation of the Pneumococcal
polysaccharide Response
 Age > 2 years of age : mostly developed protective titers
to at least some serotypes in response to natural
infection
 Absence of protective antibodies to all serotypes tested
at baseline  unusual

 Recently, low antibody concentrations following natural
infection or PCV administration  not specifically
define a SAD phenotype
 Previously, Serotype-specific antibody concentrations
 Compare preimmunization to postimmunization : normal
to be a 4-fold increase in the concentration
 Other sources : 2-fold increase.

 Pitfalls
1. If the baseline > 4 mg/mL  may not produce a
significant increase in titer on vaccine challenge
2. If a baseline titer exceedingly low and increase of
several fold  not protective range

 Now, percentage of serotype-specific titers measured
(titers to serotypes included in PPV23) within the
protective range post-PPV23
 Protective value ≥ 1.3 mg/mL and focused on PPV23-
exclusive serotypes
Acceptable percentage of protective serotypes
Age < 6 years of age 50%
Age ≥ 6 years of age 70%

 Patients who are PCV naïve:
 All PPV23 serotype titers measured : the percentage of
these serotypes that are in the protective range post-
PPV23 is considered the percentage response
 Patients who have previously received PCV:
 At least 7 PPV23-exclusive serotypes should be measured.
 Evaluation based on the PPV23-exclusive serotypes

 Based on antibody response to individual
PPV23 serotype
 All phenotypes assume an abnormal pattern
of infection
Diagnosis of Specific Antibody
Deficiency Phenotypes

Diagnosis of Specific Antibody
Deficiency Phenotypes

Management
 Based on severity of infections
1. Additional immunization
2. Antibiotic prophylaxis and treatment
3. Immunoglobulin therapy

Immunization
 In memory phenotype
 Reimmunization with PPV23
 Repeated administration of polysaccharide vaccines :
limited data
 Most recommendation
 waiting > 1 year before administration of a second dose of
PPV23
 administration only transient initial response groups

Immunization
 Multiple, repeat PPV23 administration : not
likely to be effective and recommended
 Patients who fail to respond to the initial
challenge with PPV23 may respond to the
conjugated vaccine
 80 - 90% in SAD : strong serologic response
to PCV

Immunization
 PCV13 : recommended
 Evidence of PCV may prime the response to a
subsequent dose of PPV23
 If patients have failed to respond to PPV23 :
reimmunization with PPV23 after 1 year may
produce a better response by taking advantage
of the priming effect of the conjugate vaccine

Antibiotic
 Antibiotic prophylaxis : especially in young
patients who are likely to outgrow
 Type of antibiotic : trimethoprim-
sulfamethoxazole or amoxicillin and intranasal
mupirocin ointment for adjunct therapy

Antibiotic
 Treatment with high doses of antibiotics for
a period of at least 2 weeks
 Prevents infectious complications
 Complicated chronic sinusitis
 Bronchiectasis

Immunoglobulin Replacement Therapy
 In mild, moderate, or memory phenotypes with
persistent infections despite appropriate management
 In severe phenotype
 Patients who have already developed permanent
organ damage

 May prevent complications
 Hearing loss
 Sinus damage
 Bronchiectasis
 Significantly affecting quality of life
 Reducing the need for excessive medical
visits and missed work/school

 Recommended immunoglobulin starting dose : 400 -
600 mg/kg/ month by intravenous or subcutaneous
 Patients who experience repeated breakthrough
infections or have bronchiectasis require higher doses
and/or shorter intervals between doses
 Treatment will be discontinued after a period of 1 - 2
years : should be scheduled during the spring or
summer seasons

 Reevaluation immune response 4 - 6 months after
discontinuation of immunoglobulin replacement
 Some need to receive immunoglobulin infusion
indefinitely
 Adults and adolescents with the severe phenotype
 Patients with permanent organ damage

 6 months after the final immunoglobulin dose 
evaluation of antibody- mediated immunity
 If pneumococcal titers are low  administered additional
dose of PPV23 and measuredt post-PPV23 titers 4 weeks
after immunization
 Many children do not require further immunoglobulin
replacement therapy
 Some continue to have persistent infections and need to
resume the infusions without waiting 6 months for the
repeat laboratory evaluation

Prognosis
 Immunologic phenotypes may be transient or
permanent
 Transient forms : children 2 - 5 years of age
 Permanent form : good prognosis with proper
management
 Undiagnosed or improperly treatment  permanent
sequelae

Prognosis
 Outgrow SAD : continue to be monitored at
least annually and educated to contact the
immunologist if an abnormal pattern of
infection returns
 Older patients : monitored closely, may
eventually develop common variable
immunodeficiency

Conclusion
 Antibody defects
 Failure of immunologic response to polysaccharide
antigens with otherwise intact immunity
 Recurrent sinopulmonary infections
 Wide spectrum of clinical and immunologic phenotypes
 Permanent organ damage : bronchiectasis is possible

Conclusion
 Strongly advised regarding the approach to patients
who may fit a mild phenotype, or have a borderline
diagnosis, but manifest a significant pattern of
infections
 Immunologic severity does not correlate with clinical
severity in many patients
 Treatment should be tailored based on the clinical
manifestations

Specific antibody deficiency

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