FUNCTION OF A RARE VARIANT OF ALPHA-1-ANTITRYPSIN, PHENOTYPE PI-E(FRANKLIN)-S, A POOR INHIBITOR OF HUMAN NEUTROPHIL ELASTASE

A 31-year-old woman with the rare alpha-1-antitrypsin (A1AT) phenotype Pi E(Franklin) S presented to this laboratory. Since little is known about the E(Franklin) protein, a study was established to investigate the biochemical properties of this glycoprotein, notably its inhibitor y activity against human neutrophil elastase (HNE), compared with that of the more common A1AT variants M and Z. The serum A1AT level of 1.8 g/l (reference range 0.8-2.2 g/l) and anti-neutrophil elastase capaci ty (ANEC) value of 28 mu M (reference range 15-42 mu M) of this varian t were normal. However, the association rate constant (AC) of the isol ated and purified E(Franklin) protein 2.7 (0.4)x10(6) M(-1) s(-1) at 2 5 degrees C was significantly lower com pared with that in the normal M variant 9.1 (0.9)x10(6) M(-1) s(-1), This implies that this form of A1AT is expressed at normal levels in serum but is functionally impair ed as an inhibitor of HNE, The in vivo serum inhibition time of HNE wa s estimated to be 66 ms for the purified E(Franklin) protein compared with 20 ms for the M protein. While this protein is not an efficient i nhibitor of HNE, there are sufficient molecules in the serum to achiev e 100% inhibition of HNE and to protect the lung against proteinase at tack. In conclusion, individuals who inherit the rare E(Franklin) vari ant in conjunction with the M or S A1AT molecules do not appear to hav e a high risk for the development of emphysema.