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Alpha 2-macroglobulin-kallikrein complexes detect contact system activation
in hereditary angioedema and human sepsis
N Kaufman, JD Page, RA Pixley, R Schein, AH Schmaier and RW Colman
Thrombosis Research Center, Temple University School of Medicine,
Philadelphia PA 19140.
Activation of the contact system has been documented in severe sepsis and
hereditary angioedema, but a sensitive, specific, and quantitative assay
for assessing the degree of involvement of this proteolytic enzyme cascade
is not yet available. We have developed a quantitative sandwich
enzyme-linked immunosorbent assay (ELISA) for the alpha 2-
macroglobulin-kallikrein (alpha 2M-Kal) complex using an F(ab')2 derivative
of a monospecific polyclonal antibody against alpha 2 M as the capture
antibody and a unique murine monoclonal antibody, 13G11, against the heavy
chain of kallikrein as the detector antibody. The assay does not detect
complexes in normal plasma but reacts with complexes generated by
activating normal plasma with dextran sulfate at 4 degrees C in a range of
5 to 375 nmol/L. A close correlation of the ELISA with an amidolytic assay
for alpha 2M-Kal was documented. Patients with sepsis syndrome but negative
bacterial blood cultures did not show elevated plasma complexes, whereas a
majority of those with positive blood cultures did show modest elevation
and a single patient with septic shock showed a very high level of alpha
2M-Kal complex. Similarly, a patient with classic hereditary angioedema
(HAE) showed increased concentration of complexes on three separate
occasions during attacks but normal levels between attacks. Two other HAE
patients did not show elevated levels at quiescent periods. The ELISA for
alpha 2M- Kal appears to be sensitive, specific, and quantitative, and it
can be used to reflect the degree of contact system activation in human
sepsis and in HAE attacks.
Volume 77,
Issue 12,
pp. 2660-2667,
06/15/1991
Copyright © 1991 by The American Society of Hematology
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