Anti-zeta antibody screening for alpha-thalassemia using dried filter paper blood.
The most common alpha-thalassemia in Southeast Asian or Southern Chinese populations is the (--SEA) double alpha-globin deletion. Couples heterozygous for (--SEA) have 25% risk for hydrops fetalis from loss of all four alpha-globin genes. The (--SEA) deletion spares the embryonic zeta-globin genes and causes traces of zeta-peptide to persist throughout life. A colorimetric monoclonal anti-zeta antibody test for raised zeta-peptide has detected the (--SEA) deletion in liquid blood samples, but not deletions of the entire alpha-globin region with loss of the zeta-globin genes. Eluates from dried blood spots had the same anti-zeta antibody color reaction as whole blood, even after storage at 4 degrees C for up to 77 days. The anti-zeta antibody test was positive in 24 of 91 microcytic samples (mean corpuscular hemoglobin < 24 pg), including four with iron deficiency; it was negative in 26 provisionally diagnosed alpha-thalassemia-1 heterozygotes and all 32 nonmicrocytic samples. Southern blot analysis and a specific SEA-polymerase chain reaction test confirmed that 18 anti-zeta antibody-positive samples and 1 anti-zeta antibody-negative sample had the (--SEA) deletion. Two anti-zeta antibody-negative microcytic samples had the (--Fil) total alpha-globin region deletion, 2 had single alpha-gene deletions, 22 others may also have had a total alpha-region deletion. Hence specificity was very high and sensitivity was 95%. The anti-zeta antibody test can detect the (--SEA) deletion in dried blood samples, even after prolonged storage. This simple inexpensive test can conveniently screen samples collected at a distance from a central laboratory.
Harada
F
F
Department of Genetics, University of Hawaii, Honolulu 96826.
Ireland
J H
JH
Hsia
Y E
YE
Chui
D H
DH
D000911:Antibodies, Monoclonal; D004247:DNA / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D005914:Globins / Q000235:genetics; D006801:Humans; D015160:Hydrops Fetalis / Q000175:diagnosis; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012698:Serologic Tests / Q000379:methods*; D017085:alpha-Thalassemia / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D005914:Globins; D004247:DNA