Biochemistry of hpogammaglobulinemia

1. HYPOGAMMAGL
OBULINEMIA

2. OUTLINE
• INTRODUCTION
• DEFINITION OF HYPOGAMMAGLOBULINEMIA
• METHOD OF INVESTIGATION
• CAUSES OF HYPOGAMMAGLOBULINEMIA
• TREATMENTS

3. INTRODUCTION
Gamma globulins are soluble, high molecular
weight globular proteins with a typical weight of
about 120 kDa and above.
The normal level of plasma gamma globulins
is 20-30g/l and they are the only plasma
proteins that do not originate from the liver.

5. DEFINITION OF
HYPOGAMMAGLOBULINEMIA
Hypogammaglobulinemia is a pathology
characterized by a decrease in the level of plasma
gamma globulins that results from deficiency in B
lymphocytes.

6. PLASMA PROTEINS INVESTIGATION

7. A patient with Hypogammaglobulinemia is
marked by a consequent decrease in the level of
gamma globulins as shown by the densitometer
scanning below.
As mentioned above
the main cause of this
decrease is the
reduction in the
number of B
lymphocytes produced
which may arise due to
different reasons.

8. CAUSES
- Hypogammaglobulinemia may be caused by primary
(congenital) or secondary (acquired) disorders.
- The primary (congenital disorders include:
A) X-linked agammaglobulinemia (XLA, Bruton
agammaglobulinemia)
This is a genetic disorder that affects mainly boys.
The symptoms start between the 7-9 months after a
significant decline in maternal antibodies and is
characterized by recurrent bacterial infections commonly
H influenzae B (HIB) and S pneumoniae.
This disorder has been attributed to mutation in
Tyrosine kinase gene and protein.

9. B) Autosomal recessive agammaglobulinemia (ARA)
The implicated molecules or genes include
IgM heavy chain, Ig alpha, surrogate light chain, B
cell linker protein (BLNK)
C) Specific antibody deficiency (SAD) or specific
polysaccharide antibody deficiency (SPAD)
SAD is characterized by total levels of IgG, IgA,
and IgM within the normal range, but with an
inability to make appropriate quantities of specific
antibodies and/or to retain memory of
polysaccharide vaccines.

10. D) Hyper-IgM syndromes (including deficiencies of
CD40 ligand (CD154), activation-induced cytidine
deaminase [AID], and uracil-nucleoside-glycosylase
[UNG]):
This is a heterogeneous group of disorders in
which normal or elevated IgM levels are found along
with low levels of IgA, IgG, and, sometimes, IgE.
E) Common variable immunodeficiency (CVID)
CVID is usually differentiated from XLA and
autosomal recessive agammaglobulinemia by the
presence of B-cells, visible tonsils or a history of
tonsillectomy, and palpable or even enlarged lymph
nodes.

11. F) Transient hypogammaglobulinemia of
infancy
This occurs when there is a delay in the production of IgG
in the baby after exhaustion of the maternal IgG around
the 6th month of age. The reason for this delay is still not
well understood but the child during this period remains
susceptible to different kinds of infections.
G) Wiskott-Aldrich syndrome
This defined by mutation of WAS protein on the
short arm of chromosome X and characterized by
eczema, petechiae, bruising or bleeding, recurrent severe
infections (including opportunistic infections)
autoimmune diseases, and B-cell lymphomas.

12. The secondary gamma globulinemia are present in:
- Nephrotic syndrome: Decreased levels of IgG can
appear with normal levels of IgA and IgM in the
nephrotic syndrome.
- Protein-losing enteropathy: This occurs because of
intestinal lymphatic blockade with resulting
leakage of lymphatic fluid and cellular components
into the lumen.
- Immunosuppressive therapy
- Lymphoproliferative malignancies (leukemia &
leukocytosis B-CLL cells inhibit Ig secreting plasma
proteins)
- Prematurity in infants:

13. TREATMENT
Immunoglobulin replacement therapy is the
most effective therapy against all forms of
Hypogammaglobulinemia and can be achieved
mainly by vaccination ( PASSIVE AND ACTIVE).
Other syndromes that can not be stabilized by
Vaccination e.g WAS are resolved mainly by
bone marrow transplantation,

14. THANKS FOR
YOUR ATTENTION