Immunoblotting of plasma in a pregnant patient with hereditary angioedema.
Hereditary angioedema (HAE), an autosomal disorder caused by a deficiency of C1 inhibitor, is characterized by attacks of localized swelling, laryngeal edema, or abdominal pain. Plasma samples from one pregnant patient were studied serially by functional and quantitative immunochemical assays as well as immunoblot assays for high molecular weight kininogen (HMWK) and/or prekallikrein/kallikrein (PK/K). An immunoblot of this patient's HMWK from plasma obtained before she became pregnant and when she was well revealed that it was mostly an intact protein of 120 kd, similar to immunoblot results of normal plasma HMWK. In plasma samples taken throughout her pregnancy, before, during, and after clinical attacks of angioedema, all of her plasma HMWK was shown to be cleaved into the 45 kd light chain form. After delivery of the infant the 120 kd form of intact plasma HMWK returned to her plasma. In comparison, immunoblot studies on 21 normal and abnormal pregnancies revealed that plasma HMWK was an intact protein at 120 kd. That this patient's plasma during her pregnancy was contact activated was determined by additional immunoblot studies for PK/K. Immunoblot assay for plasma PK/K revealed kallikrein-alpha 2-macroglobulin complexes and a 50 kd PK/K form seen only in activated plasma samples. The findings of kallikrein-alpha 2-macroglobulin complexes and a 50 kd PK/K form disappeared after delivery. These combined studies on this patient show that the structures of HMWK and prekallikrein as indicated by immunoblot assays were altered during pregnancy. Immunoblot assays for detection of changes in the structure of HMWK and prekallikrein may be objective laboratory studies for documenting clinical attacks of hereditary angioedema, their onset, and their resolution.
Chhibber
G
G
Department of Obstetrics and Gynecology, Albert Einstein Medical Center, Philadelphia, PA.
Cohen
A
A
Lane
S
S
Farber
A
A
Meloni
F J
FJ
Schmaier
A H
AH
D000328:Adult; D000799:Angioedema / Q000097:blood* / Q000235:genetics / Q000276:immunology; D003174:Complement C1 Inactivator Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007610:Kallikreins / Q000276:immunology / Q000378:metabolism; D007704:Kininogens / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood*; D000511:alpha-Macroglobulins / Q000276:immunology / Q000378:metabolism
D003174:Complement C1 Inactivator Proteins; D007704:Kininogens; D000511:alpha-Macroglobulins; D007610:Kallikreins