Cryoglobulins . Cryoglobulin Outline. I. Cryoglobulins Background II. Types of antibody classes associated with Cryoglobulins III. The diseases associated with Cryoglobulins IV. Cryoglobulin disease treatments V. The Cryoglobulin test principle.
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I. Cryoglobulins Background
II. Types of antibody classes associated with
III. The diseases associated with Cryoglobulins
IV. Cryoglobulin disease treatments
V. The Cryoglobulin test principle
VI. The Preparation of Specimen
VII. The Collection Procedure
VIII. The Cryoglobulin Test Procedure
IX. Quality Control Test
X. Test Results
precipitate reversibly at lowered temps.
Recent studies have shown that the temperature at which cryoglobulins precipitate varies with the total protein concentration. Higher concentrations of protein in a sample increases the temperature at which the cryoglobulins precipitate.
Cryoglobulins are made up of monoclonal
antibodies IgM or IgG, rarely IgA. IgM tends
to precipitate at lower temperatures than does
Occasionally, IgM macroglobulin is both cryo precipitable and capable of cold induced antibody mediated agglutination of red cells.These are referred to as cold agglutinins. Not all cryoglobulins are cold agglutinins because they do not share some of the antibody characteristics of cold agglutinins.
Cryoglobulins are classified into three types
based on their composition.
Type I - is made up of a monoclonal single
homogeneous immunoglobulin usually IgM or
IgG. The Cryoglobulin concentration is
usually high, greater than 5 mg/ml.
Type II - are classified as mixed cryoglobulins
Type III - are mixed cryoglobulins that lack
a monoclonal component.
Examples of Type I Cryoglobulins disorders
include Waldenstrom’s Macroglobulinemia,
Paroxysmal Cold Hemoglobinuria, and
Idiopathic Nonmalignant Monoclonal
Symptoms of Type I Waldenstrom’s
Macroglobulinemia include hyperviscosity of
the blood, cold urticaria, Raynaud’s
Phenomenon, Purpura, and Cutaneous
Vasculitis with or without ulcerative retinal
hemorrhage. These monoclonal antibodies
are IgM or IgG.
In the case of Waldenström's Macroglobulinemia, these types of cryoglobulins precipitate due to cold exposure and may induce partial or complete occlusion of small blood vessels.
Idiopathic nonmalignant monoclonal
cryoglobulinemia may be related to a unique
gene arrangement in certain individuals.
Studies have shown that this may relate to the
high rate of synthesis of cryoglobulins in
nonmalignant B cells.
Paroxysmal Cold Hemoglobinuria is caused by a Type I cryoglobulin that lyses red blood cells at 37 degrees Celsius. The key point is that compliment was attached at 0 - 4 degrees C. When the temperature rose, red blood cells lysed. The antibody specificity is directed against the red blood cell antigen P3.
Symptoms of (PCH) include, discoloration of
the area varying from pale gray to dark blue-
violet. Usually the areas are the fingers, toes,
earlobes, and the nose. Pain and numbness is
associated with PCH as well as anemia.
Age groups most susceptible for PCH are the elderly population between the ages of 60 - 80 years old.
Treatment for Type I Cryoglobulin disorders are designed to eliminate the immune complexes between Cryoglobulin antibodies and antigens. This can be done by prewarming of blood in transfusions, and administering of steroids. Splenectomy has been performed in selected idiopathic cases.
These disorders are associated with a major disorder called Essential Mixed Cryolobulinemia or (EMC).
The symptoms for the Type II Cryoglobulin
disorder, EMC include the following:
Note: Essential Mixed Cryoglobulinemia or EMC is slightly more common in females than males. In fact, females that are between the ages of 30 - 50 years of age are more susceptible.
Treatment for EMC have involved the following:
Type III Cryoglobulins are very rare occurrences and occur in low concentrations. They are usually resolved when the precipitate dissolves.
Cryoglobulins are abnormal immunoglobulins that form complexes and precipitate out of serum at low temperatures and redissolve upon warming or returning to room temperature. The Cryoglobulin test detects antibodies in the blood that may cause sensitivity to low temperatures.
The specimen required is whole blood. The sample is brought to the laboratory immediately after drawing. The specimen must not be refrigerated before the test.
. Tubes for collection should not be anticoagulated blood since the use of plasma may result in the development of cold-precipitable fibrinogen, (cryofibrinogen) or heparin-precipitable
A known positive patient sera may be used as
a positive control when available. There is no
commercial material available.
Positive test results of less than 1 mg/ml is
considered normal. Positive test results of
concentrations of Cryoglobulins greater than 1
mg/ml is indicative of disease. If positive, the
exact composition of protein is detected by
The test for detecting cryoglobulins is based
on the effects of temp and their solubility.