ANTIBODY DEFICIENCY SYNDROMES

doi:10.1016/S0031-3955(05)70269-8

Pediatric Clinics of North America

Volume 47, Issue 6, 1 December 2000, Pages 1225-1252

https://doi.org/10.1016/S0031-3955(05)70269-8 Get rights and content

Antibody deficiencies are, by far, the most commonly reported immunodeficiencies worldwide.20, 24, 40, 41, 69 The spectrum of antibody deficiencies ranges from severe deficiencies of all immunoglobulins (i.e., agammaglobulinemia) to milder, but clinically relevant, deficiencies of specific antibodies in patients with normal immunoglobulin concentrations. The prevalence of antibody deficiency syndromes typically increases with decreasing severity. IgA deficiency, which occurs in some asymptomatic individuals, is the commonest immunodeficiency.²² The various types of antibody deficiency are best understood after a brief review of the development and function of antibody-mediated immunity.

Section snippets

DEVELOPMENT OF ANTIBODY-MEDIATED IMMUNITY

B cells mature in an antigen-independent manner from stem cells undergoing different phases of maturation (Fig. 1). Various stages of differentiation are recognized by the appearance of immunoglobulin chains within the cell and later by complete cell-surface immunoglobulins with heavy and light chains expressed on the cell surface.¹¹ The development of an immature B cell to the mature form is dependent on the normal activity of a specific B cell tyrosine kinase (Btk).

Further proliferation and

GENERAL EVALUATION OF ANTIBODY-MEDIATED IMMUNITY

Immunologic methods can be classified as those identifying (1) phenotypic abnormalities and (2) genetic and molecular defects (Fig. 3):

Phenotype evaluation
- Serum immunoglobulin levels
- IgG subclasses
- Specific antibodies
  - Antiprotein antibodies
    Tetanus and diphtheria antibodies
    H. influenzae antibodies
  - Antipolysaccharide antibodies
    Isohemagglutinins
    Pneumococcal polysaccharide antibodies
  - Antibacteriophage antibodies
- B-cell enumeration
- Evaluation of

RELATIONSHIP BETWEEN DIFFERENT FORMS OF ANTIBODY DEFICIENCY

IgA deficiency and CVID may occur in multiple members of involved families, and serum immunoglobulin concentrations may increase or decrease over time, leading to changes from IgA deficiency to CVID.¹⁸ In these families, IgA and CVID may represent the polar ends of a clinical continuum of immune abnormalities.²¹

Several forms of antibody deficiency are transient, and the phenotype of other types of antibody deficiency change over time5, 18, 32, 37:

Age-related transient deficiencies

SUMMARY

Antibodies have a crucial role in protecting against infections, and antibody deficiencies are the commonest primary and secondary immunodeficiencies. Antibody deficiencies may be the only abnormality present in a patient, or they may be present and aggravate the symptoms of various other conditions.28, 44 Because the presence of an antibody deficiency is difficult to predict from clinical presentation, physicians should perform an evaluation of antibody-mediated immunity, even knowing that, in

ACKNOWLEDGMENT

The authors thank our editorial consultant in the Division of Allergy/Immunology, Louisiana State University Health Sciences Center, Patricia A. Giangrosso, for her invaluable help in preparing the manuscript.

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Cited by (72)

Specific antibody deficiency with normal immunoglobulin concentration in children with recurrent respiratory infections
2015, Allergologia et Immunopathologia
Citation Excerpt :
This set of syndromes share certain common characteristics, such as most patients have completely normal cellular immunity, phagocytic function, and complement levels; the illnesses are characterised by recurrent bacterial respiratory infections (rhinosinusitis, otitis, bronchitis, and pneumonia); their molecular basis is poorly known; very few require intravenous immunoglobulin; and the long-term prognosis is generally favourable.8 Children over two years of age who suffer repeated respiratory infections (otitis media, sinusitis, pneumonia) due to capsular pathogens, requiring frequent antibiotic treatment, should be tested for defective anti-polysaccharide antibody response to screen for specific antibody deficiency if they have normal immunoglobulin and IgG subclass levels and no other identified immunodeficiency.9 The objective of this study is to evaluate the response to polysaccharide capsular pneumococcal antigens, in order to screen for selective antibody deficiency with normal immunoglobulin (SAD) in children with recurrent respiratory infections.
Response to polysaccharide antigens is a test to evaluate the immunological competence of children with recurrent respiratory infections (RRI) of unknown cause and no other immune system abnormality. In order to detect specific antibody deficiency (SAD), a group of children with RRI without other immunodeficiency were prospectively studied.
We included 20 children (12 male), age range 3–14 years, with six or more annual episodes of respiratory infections (RI); one or more monthly episodes of RI during the winter months; or three or more annual episodes of lower RI. The children were immunised with 23-valent polysaccharide anti-pneumococcal vaccine, and ELISA was used to measure anti-polysaccharide IgG antibody levels for 10 pneumococcal serotypes at baseline (T0), and 45 days (T1) and one year post-immunisation (T2). Post-immunisation response above 1.3 μg/ml for more than 50% of the serotypes was considered normal for children 2–5 years, and for more than 70% of the serotypes in children older than 5 years.
At T1 19/20 children showed a normal response for their age, and only one patient showed a deficient response, suggestive of classic moderate SAD. At T2, 8/20 patients showed deficient responses, suggestive of impaired persistence of specific antibodies. There was a noteworthy association between deficient response and asthma and allergic rhinitis.
We propose first ruling out local or systemic causes, then performing serum immunoglobulin IgM, IgG, IgA, IgE and IgG subclass levels, and finally measuring response to polysaccharide pneumococcal antigens for detection of SAD.
Specific Antibody Deficiency with Normal Immunoglobulins
2014, Stiehm's Immune Deficiencies
Specific antibody deficiency (SAD) is a common antibody immunodeficiency defined as a poor antibody response to unconjugated pneumococcal polysccharides present in the 23-valent pneumococcal vaccine (PPV23). All immunoglobulin concentrations, including IgG subclasses, are normal, and antibody responses to protein antigens (e.g., tetanus toxoid, diphtheria toxoid) are also normal in most patients. In some patients with SAD, the response to the pneumococcal conjugate vaccines is also normal. The clinical manifestations of specific antibody deficiency include recurrent otitis media; sinopulmonary infections such as sinusitis; bronchitis; and pneumonia. In SAD patients these infections are more frequent or severe than infections observed in normal children or adults. There is not a single pathogenic mechanism for specific anti-polysaccharide antibody deficiencies. The variable conditions in which an inability to respond to polysaccharides is found suggest that many different immunologic phenotypes may lead to the same clinical phenotypic antibody deficiency. The interpretation of anti-pneumococcal antibody concentration results is based on increased post-immunization antibody concentrations over pre-immunization concentrations (immune response) and on the final post-immunization antibody concentrations, regardless of increase from pre-immunization concentrations (antibody concentration).
The management of SAD, including prevention and treatment of recurrent infections, can be classified into the following broad categories: additional immunization, antibiotic prophylaxis and treatment, and immune serum globulin therapy. The immunologic phenotypes of SAD may be transient or permanent. Even in permanent phenotypes, the natural history of SAD is usually benign with proper management of these patients. Further insights into the pathogenesis of this immunodeficiency will allow further understanding of the correlation between immunologic and clinical phenotypes of SAD.
Treatment of hypogammaglobulinemia in adults: A scoring system to guide decisions on immunoglobulin replacement
2013, Journal of Allergy and Clinical Immunology
Reduced serologic response to mumps, measles, and rubella vaccination in patients treated with intravenous immunoglobulin for Kawasaki disease
2013, Journal of Allergy and Clinical Immunology
When should immunologic explorations be carried out in children with suspicion of primary immunodeficiency?
2013, Archives de Pediatrie
L’identification d’un déficit immunitaire héréditaire est importante dans le pronostic et la prise en charge des patients atteints de ces maladies génétiques rares. Pour les diagnostiquer, des examens simples sont à réaliser en première intention devant des infections sévères, récurrentes ou inhabituelles. Ces examens de routine sont l’hémogramme, le dosage pondéral des immunoglobulines, les sérologies post-vaccinales ou post-infectieuses. Ils orientent le diagnostic avec l’analyse conjointe des antécédents infectieux et l’examen clinique. Ils permettent ensuite de guider la prescription et la réalisation d’examens de 2^e intention en fonction du type de déficit immunitaire héréditaire suspecté.
The identification of primary immunodeficiency is important in the prognosis and treatment of patients with these rare genetic diseases. For their diagnosis, simple screening explorations need to be carried out in case of severe, recurrent, and/or unusual infections. These include the whole blood cell count, plasmatic immunoglobulin levels, and postimmunization and/or post-infectious serologies. These examinations are used to guide the diagnosis with the joint analysis of patient's medical history, the clinical examination, and screening of biological results. They will then guide the prescription of more specific second-line explorations depending on the type of primary immunodeficiency suspected.
Assessment of functional immune responses
2013, Clinical Immunology: Principles and Practice: Fourth Edition

View all citing articles on Scopus

: Address reprint requests to Ricardo U. Sorensen, MD Division of Allergy/Immunology Department of Pediatrics Louisiana State University Health Science Center 1542 Tulane Avenue New Orleans, LA 70112–2822

^*: Division of Allergy/Immunology, Department of Pediatrics and the Allergy/Immunology Training Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana

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ANTIBODY DEFICIENCY SYNDROMES

Section snippets

DEVELOPMENT OF ANTIBODY-MEDIATED IMMUNITY

GENERAL EVALUATION OF ANTIBODY-MEDIATED IMMUNITY

RELATIONSHIP BETWEEN DIFFERENT FORMS OF ANTIBODY DEFICIENCY

SUMMARY

ACKNOWLEDGMENT

J Allergy Clin Immunol

J Allergy Clin Immunol

Clin Immunol Immunopathol

J Allergy Clin Immunol

Clin Immunol

Clin Immunol Immunopathol

Ann Allergy

Ann Allergy Asthma Immunol

Lancet

J Allergy Clin Immunol

J Pediatr

Blood

J Allergy Clin Immunol

Pediatr Clin North Am

An immunodeficiency characterized by impaired antibody responses to polysaccharide

N Engl J Med

Selective IgA deficiency: Presentation of 30 cases and a review of the literature

Medicine

Transient hypogammaglobulinemia of infancy with severe bacterial infections and persistent IgA deficiency

Isr J Med Sci

Reference ranges for IgG subclasses in preschool children

Arch Dis Child

Efficacy, safety and immunogenicity of heptavalent penumoccocal conjugate vaccine in children

J Pediatr Infect Dis

Current concepts. B lymphocytes: Normal development and function

N Engl J Med

Clinical and immunologic analyses of 103 patients with common variable immunodeficiency

J Clin Immunol

Selective IgA deficiency and neoplasia

Vox Sang

Incidence of cancer in 98 patients with common varied immunodeficiency

J Clin Immunol

Antibody response to pneumococcal vaccination in children younger than 5 years of age

J Infect Dis

Pulmonary manifestations of hypogammaglobulinaemia

Thorax

Selective deficiency in pneumococcal antibody response in children with recurrent infections

Ann Allergy Asthma Immunol

Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature

Medicine

Primary immunodeficiency disorders in Sweden: Cases among children, 1974–1979

J Clin Immunol

Genetic approach to common variable immunodeficiency and IgA deficiency

Selective IgA deficiency

Common variable hypogammaglobulinemia in children: Clinical and immunologic observations in 30 patients

Am J Dis Child

Primary immunodeficiency syndrome in Japan: I. Overview of a nationwide survey on primary immunodeficiency syndrome

J Clin Immunol

Primary hypogammaglobulinaemia: A survey of clinical manifestations and complications

Q J Med

Mutation screening of the BTK gene in 56 families with X-linked agammaglobulinemia (XLA): 47 unique mutations without correlation to clinical course

Pediatrics

Age-related changes in serum immunoglobulins in patients with familial IgA deficiency and common variable immunodeficiency (CVID)

Clin Exp Immunol