B Cell and Immunoglobulin Immunode

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B cell and immunoglobulin immunode
1\:500,000; characterised by recurrent infections.
X-linked agammaglobulinaemia\: X-linked recessive; mutations in Bruton tyrosine kinase gene; presents in infancy with
recurrent infections; smaller secondary lymphoid organs; lacks mature B cells; managed with lifelong IVIG.
Common variable immunode
with recurrent infections, autoimmune disease, and malignancy; normal B cell count; managed with IVIG and
multidisciplinary approach.
Hyper-IgM syndrome\: high IgM, low other antibodies; defect in class switching; opportunistic infections in
life; liver disease, malignancy; normal B cells; managed with IVIG, antibiotic prophylaxis, stem cell transplant.
IgA de
diagnosed if serum IgA \<7 mg/dL; managed by treating speci
Transient hypogammaglobulinaemia of infancy\: reduced IgG levels after 6 months of age; presents with respiratory,
gastrointestinal infections, allergies; monitored with IgG levels every 4-6 months; usually normalises by age
Laboratory features\:
X-linked agammaglobulinaemia\: low B cells, all immunoglobulins low
CVID\: normal B cells, all immunoglobulins low
Hyper-IgM syndrome\: normal B cells, high IgM, low IgG/IgA/IgE
IgA de
Transient hypogammaglobulinaemia of infancy\: normal B cells, IgG low, IgM/IgA normal or low
Management\:
X-linked agammaglobulinaemia\: lifelong IVIG, avoid live vaccines
CVID\: IVIG, avoid live vaccines, manage autoimmune disease
Hyper-IgM syndrome\: IVIG, antibiotic prophylaxis, stem cell transplant
IgA de
Transient hypogammaglobulinaemia of infancy\: monitor IgG levels, avoid infections, postpone live vaccines
Article 🔍
A comprehensive topic overview

Introduction

B cell and immunoglobulin immunode
The prevalence of primary immunode
population of the Western world, and B cell immunode1
In general, these
syndromes are characterised by recurrent infections.
This article will discuss the unique features and management of the di
immunodeX-linked agammaglobulinaemia
X-linked agammaglobulinaemia (or Bruton agammaglobulinaemia) is inherited most often in an x-linked recessive
pattern. It can be distinguished from other B-cell immunode
Aetiology
Mutations in the Bruton tyrosine kinase gene on the X chromosome are responsible for causing the disorder. This gene is
crucial in B cell development, and mutations in the gene result in a lack of mature B cells in circulation and a lack of
antibody production.
2,3
Clinical features
Most cases present in infancy after maternal IgG begins to disappear and recurrent infections develop in the
years of life. These infections are most often caused by staphylococcus, streptococcus, Haemophilus, and Giardia and can
3
include ear infections, respiratory tract infections, sinus infections, and diarrhoea .
A notable feature on examination of patients with x-linked agammaglobulinaemia is smaller than normal secondary
lymphoid organs (e.g. tonsils and lymph nodes) resulting from a lack of B cell development.
2
Laboratory features
X-linked agammaglobulinaemia is characterised by a lack of B cells in circulation, leading in turn to a reduction in the
number of immunoglobulins of every class in circulation.
2,3
Management
Patients with X-linked agammaglobulinaemia require lifelong intravenous immunoglobulin replacement. This is
successful in preventing infection in most cases. Live-attenuated vaccines must be avoided in these patients because of
the risk of infection.
3

Common variable immunode

Common variable immunode
preserved, antibody production is impaired, and there are low levels of immunoglobulins in the blood. Unlike other B cell
immunode
4
Aetiology
CVID results from impaired immunoglobulin production by plasma cells. The exact is unknown, however, in 10% of cases a
genetic basis has been established, and several genes involved in B cell development and class switching are theorised to
be a
4
Clinical features
CVID presents in early adulthood with recurrent infections. These are most often sinusitis, respiratory tract infections,
gastrointestinal infections causing diarrhoea, and infections caused by opportunistic organisms. CVID is also associated
with an increased incidence of autoimmune disease and malignancy.
5
Laboratory features
In CVID, a normal B cell and plasma count is observed. However, a reduced level of all immunoglobulin classes is seen.
5
Management
CVID patients require a multidisciplinary approach to manage both the infectious complications as well as the
autoimmune and malignant complications of the disease. They will require intravenous IgG infusions and must avoid live
attenuated vaccines for risk of infection.
5Hyper-IgM syndrome
Hyper-IgM syndrome is an immunode
defect in antibody class switching results in high levels of IgM antibodies and low levels of other antibody classes (IgG,
IgA, etc.).
Aetiology
Hyper-IgM syndrome occurs because of a defect in B cell class switching. Normally, the interaction between activated T-
cells and B cells will stimulate B cells to proliferate and switch from producing IgM to producing other immunoglobulins
including IgG and IgA antibodies.
De
cause hyper IgM syndrome. Inheritance patterns of mutations in these genes is x-linked for CD40L, and mostly autosomal
recessive for the rest.
4
Clinical features
Opportunistic infections within the
Histoplasma) are common in hyper-IgM syndrome. In particular, cryptosporidium infection and its associated
complications in the biliary system are often seen.
4,6
Other notable features common in patients with hyper IgM syndrome are liver disease resulting from cytomegalovirus and
hepatitis, mucosal diseases, and a higher incidence of malignancies.
4
Many patients with hyper-IgM syndrome will die in childhood or will develop malignancy and chronic complications in
adulthood.
6
Laboratory features
The typical laboratory
and reduced IgG, IgA, and IgE molecules.
Flow cytometry can be performed to identify the lack of cell surface markers that may cause hyper IgM syndrome (e.g.
lack of CD40L on T cells).
6
Management
Patients with hyper-IgM syndrome should receive IVIG replacement, trimethoprim/sulfamethoxazole antibiotics to prevent
P n e u m o c y s t i s j i r o v e c i i infection, and should take precautions to avoid exposure to cryptosporidium. The de
treatment is a hematopoietic stem cell transplant.
6

IgA de

IgA de
a secreted immunoglobulin, the reduction of IgA can result in gastrointestinal and respiratory infections. IgA de
the most common selective immunoglobulin de
Aetiology
The exact cause of IgA de
producing plasma cells may cause the disease.
4
Clinical features
Two-thirds of a
Common features of IgA de
illnesses (e.g. diarrhoea) and sinus infections. There is a high incidence of allergy and autoimmune diseases in children
with IgA decoeliac disease.
4,7
Rarely, IgA deanaphylactic reactions to blood transfusions from blood that contains IgA molecules.
7
Laboratory featuresFor a diagnosis of IgA de
immunoglobulins, as well as B and T cell counts, should be normal.
4
Management
Treatment should be aimed at the speci
autoimmune conditions). Patients with signi
course of prophylactic antibiotics. At present no suitable IgA replacement therapy exists.
The disease can range from mild to severe, and outcomes are di
7

Transient hypogammaglobulinaemia of infancy

Normally, a physiological nadir in immunoglobulins occurs between 3 and 6 months of age when the maternal
antibodies begin to disappear, and an infant begins producing their own antibodies.
Transient hypogammaglobulinaemia of infancy occurs when infants are found to have reduced levels of immunoglobulins
(mainly IgG) than what would be expected for an infant at greater than 6 months of age.
Aetiology
The cause is unknown. However, several proposed mechanisms include suppressive maternal antibodies persisting in the
infant circulation, abnormal B cells or T-cells failing to stimulate antibody production, and abnormal cytokine production.
8
Clinical features
Transient hypogammaglobulinaemia of infancy may present upper and lower respiratory tract infections, ear and sinus
infections, allergies, asthma, eczema, gastrointestinal di
various organs systems such as those mentioned above.
8
Laboratory features
By de
mean in the population. This typically equated to less than 400 mg/dL. IgM and IgA levels may also be reduced.
8
Imaging may show signs of infection in the respiratory tract, sinuses, or other organ systems depending on the speci
presentation.
A normal response to vaccines can be expected in children with transient hypogammaglobulinaemia of infancy.
Management
Patients can usually be monitored with IgG levels taken every 4 to 6 months. Reducing infective exposures and postponing
live attenuated vaccines until IgG levels normalise is usually enough to safely manage the condition.
In rare cases where children are failing to thrive due to recurrent infections, intravenous immunoglobulins may be
administered. Most children will attain normal IgG levels by
8

Summary tables

Table 1. Common features and management of primary B cell immunode
Clinical features Management
Transient
hypogammaglobulinaemia of
infancy
Age\: 3-6 years old
Respiratory, Gl, and sinus infections
Atopy
Check IgG levels every 4 months
Avoid infectious exposures
Postpone live vaccinesX-linked agammaglobulinaemia
Common variable immunode
(CVID)
Hyper-IgM syndrome
IgA de
Age\:
Staphylococcus, Streptococcus,
Haemophilus and Giardia infections
Smaller secondary lymphoid
organs
Age\: early adulthood
Opportunistic respiratory, GI and
sinus infections
Autoimmune disease
Age\:
Opportunistic infections (esp.
cryptosporidium)
Hepatic disease and malignancy
Age\: >4 years
Anaphylaxis to blood products
Respiratory, GI and sinus infections
Autoimmune disease
Lifelong IVIG
Avoid live vaccines
IVIG
Avoid live vaccines
Autoimmune disease management
IVIG
Antibiotic prophylaxis
De
transplant
Treatment speci
infections or autoimmune disease
Table 2. Laboratory
B cells IgM IgG IgA IgE
Transient
hypogammaglobulinaemia of
infancy
Normal/lo
Normal/lo
Normal Low
Normal/low
w
w
X-linked agammaglobulinaemia Low Low Low Low Low
Common variable
immunodeNormal Low Low Low Low
Hyper-IgM syndrome Normal High Low Low Low
IgA de

References

Knott L, Cox J. I m m u n o d e LINK]
National Institute of Allergy and Infectious Disease. X -l i n k e d a g a m m a g l o b u l i n a e m i a ( X L A ) . Last updated 2019. Available
from\: [LINK]
American Academy of Allergy Asthma and Immunology. X -l i n k e d a g a m m a g l o b u l i n a e m i a . 2022. Available from\: [LINK]
Smith T, Cunningham-Rundles C. P r i m a r y B-c e l l i m m u n o d e
[LINK]
Knott L, Cox J. C o m m o n v a r i a b l e i m m u n o d e LINK]
Fernandez J. H y p e r-I g M s y n d r o m e . Last reviewed 2021. Available from\: [LINK]
Immune DeLINK]
Immune DeLINK]Reviewer
Dr Anda Dumitrescu
Clinical Lecturer
Department of Paediatrics
University College Cork/Cork University Hospital

Related notes

Anaphylaxis
Hypersensitivity Reactions

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Contents

Introduction
X li k d l b li i
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