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APPENDIX VI
2. Systemic disease: diabetes mellitus, amyloidosis,
systemic lupus erythematosus
3. Neprotoxins and drugs: gold, mercury, penicillamine
4. Infections: poststreptococcal glomerulonephritis
5. Allergens, venoms, and vaccines
6
. Miscellaneous: toxemia of pregnancy, malignant
hypertension
The most common cause of primary nephrotic syn-
drome in adults is membranous nephropathy. It is char-
acterized by deposition of immune complex in the subep-
ithelial portion of glomerular capillary walls.
ß -Globulins
Quantitatively significant ^-globulins are composed
of transferrin,
^-lipoproteins,
complement
C3,
and
hemopexin. Transferrin, synthesized in the liver, has a
half-life of about
8 . 8
days and is an iron transport pro-
tein in serum that accounts for about 60% of the
ß
peak.
It is increased in iron deficiency anemia and pregnancy
(Chapter 29). Transferrin levels are decreased in metabolic
(e.g., liver, kidney) and neoplastic diseases. Transfer-
rin and transthyretin (Chapter 38) are both decreased in
protein-calorie malnutrition. A pattern often observed in
advanced cirrhosis is lack of separation of the
ß
peak with
the y region, described as
ß-y
bridging (Figure VI-1).
The pattern is presumably due to elevated levels of IgA.
Hypoalbuminemia is also found. Complement levels (C3
and C4) are decreased (owing to their consumption) in dis-
eases associated with the formation of immune complexes,
e.g., glomerulonephritis (acute and membranoprolifera-
tive), systemic lupus erythematosus.
-Globulins
The five major classes of immunoglobulins in descend-
ing order of quantity are IgG, IgA, IgM, IgD, and IgE
(see also Chapter 35). C-reactive protein migrates with the
/-globulins and is increased in trauma and acute in-
flammatory processes (discussed later). During an in-
tense acute inflammatory process, its concentration may
be highly elevated, giving rise to a sharp protein band that
may be mistaken for monoclonal gammopathy. Variations
in electrophoretic pattern due to /-globulins can be cate-
gorized into the following three groups.
1. Agammaglobulinemia and
hypogammaglobulinemia:
May be primary or
secondary. Secondary forms may be found in chronic
lymphocytic leukemia, lymphosarcoma, multiple
myeloma, the nephrotic syndrome, long-term steroid
treatment, and occasionally overwhelming infection.
2.
Polyclonal gammopathy:
A diffuse polyclonal
increase in /-globulin, primarily in the IgG fraction
(Figure Vl-If). Recall that in chronic stress
/-globulins are elevated. The major causes of
polyclonal gammopathy are listed below.
a.
Chronic liver disease:
An increase in polyclonal
IgG and IgA with a decrease in albumin levels is a
characteristic finding regardless of the cause. The
ß-y
bridging observed in cirrhosis is presumably
due to elevated levels of IgA that migrates to a
position between the
ß
and / region, increasing
the trough between these bands.
b.
Sarcoidosis:
The electrophoretic pattern shows a
stepwise descent of globulin fractions starting
from the /-globulins.
c.
Autoimmune disease:
This group includes
rheumatoid arthritis (increased IgA levels),
systemic lupus erythematosus (increased IgG and
IgM levels), and others.
d.
Chronic infectious disease:
This group includes
bronchiectasis, chronic pyelonephritis, malaria,
chronic osteomyelitis, kala-azar, leprosy, and
others.
3.
Monoclonal gammopathy:
Presence of narrow
protein band in the
ß-y
region may indicate the
F IG U R E V I-2
Serum electrophoretic protein patterns consisting of monoclonal
immunoglobulins identified by arrows. Normal serum pattern is identified
as 1.
