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 l 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. (C) 1994 Academic Press, Inc.