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Abstract: Poster Presentations |

DIFFERENCES IN MICROHETEROGENEITY AND NON-THERAPEUTIC PROTEIN CONTENT OF THREE COMMERCIAL PREPARATIONS OF PURIFIED HUMAN ALPHA1-PROTEINASE INHIBITOR FREE TO VIEW

Friedrich Kueppers, MD*; Utpal Patel, MS
Author and Funding Information

Temple University School of Medicine, Philadelphia, PA


Chest


Chest. 2005;128(4_MeetingAbstracts):262S. doi:10.1378/chest.128.4_MeetingAbstracts.262S
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Abstract

PURPOSE:  Three commercially available preparations of alpha1-proteinase inhibitor (A1-PI) are derived from human plasma but differ in the purification steps employed during manufacture, leading to differences in purity. As little is known about the effect of purification on biochemical composition of the final active substance, we compared their microheterogeneity and non-therapeutic protein content.

METHODS:  Zemaira® (ZLB Behring LLC) [Z], Prolastin® (Bayer Corporation) [P] and Aralast® (Baxter Inc) [A] were evaluated. Isoelectric focusing (Am J Hum Genet 1978; 30: 359-65) was performed to evaluate the relative proportion of different isoforms (M2, M4, M6) of A1-PI relative to historical values for normal serum (Scand J Clin Lab Invest 1969; 23: 97-103). Double diffusion experiments were performed to detect non-therapeutic serum proteins.

RESULTS:  The relative protein concentrations (SD) of the M2, M4 and M6 isoforms of Z were: 31.1 (4.2), 40.0 (5.0) and 19.8 (3.3) compared with 11 (2.3), 48.7 (1.5) and 40.4 (2.4) for normal serum. The corresponding values for P were: 12.6 (2.3), 39.1 (4.8), 48.3 (5.5) and those for A were: 13.0 (3.1), 48.0 (5.2) and 38.5 (4.2). Non-therapeutic serum proteins in all three preparations included alpha1-antichymotrypsin and antithrombin III. Albumin and transferrin were detected in A and P but not Z. Alpha1-acid glycoprotein was detected in Z but not A or P.

CONCLUSION:  Different purification processes appear to affect the microheterogeneity of A1-PI preparations: Z and P, but not A, displayed similar isoform content to that in normal serum. The absence of albumin in Z may account for its known high purity and solubility.

CLINICAL IMPLICATIONS:  The biochemical difference between isoforms of A1-PI is thought to reside in the carbohydrate portion, but other unidentified biochemical differences may lead to changes in isoelectric point. A1-PI glycoforms contain side chains with varying ratios of terminal moieties that could affect A1-PI tissue distribution and half-life. Long-term exposure to non-therapeutic proteins in A1-PI preparations may induce immune-mediated adverse events, as suggested by a previous study (Chest 2003; 123: 1425-34). Both findings warrant further investigation.

DISCLOSURE:  Friedrich Kueppers, Grant monies (from industry related sources) FK and UP have received funding from the Arlene Meth Fund, Baxter and ZLB Behring.

Wednesday, November 2, 2005

12:30 PM - 2:00 PM


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