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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Sep;81(18):5690–5693. doi: 10.1073/pnas.81.18.5690

Monoclonal antibody specific for the mutant PiZ alpha 1-antitrypsin and its application in an ELISA procedure for identification of PiZ gene carriers.

A Wallmark, R Alm, S Eriksson
PMCID: PMC391776  PMID: 6207528

Abstract

The PiZ genetic variant of alpha 1-antitrypsin in its homozygous form is associated with an increased risk for chronic lung and liver disease. About 5% of the population are carriers of one PiZ deficiency gene resulting in intermediate levels of plasma alpha 1-antitrypsin (PiMZ, PiSZ, PiPZ). We report the preparation of a hybridoma cell line, ATZ 11, produced by fusion of spleen cells from BALB/c mice immunized with a purified liver PiZ alpha 1-antitrypsin and Sp 2/0 Ag 14 mouse myeloma cells. ATZ 11 produces monoclonal antibodies (IgG1 kappa) specifically interacting with PiZ alpha 1-antitrypsin. These antibodies were used in an ELISA procedure permitting easy and accurate identification of PiZ gene carriers. The method is especially well-suited for studying large population samples concerning the putative relationship between intermediate alpha 1-antitrypsin deficiency and disease.

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Selected References

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  1. Berg N. O., Eriksson S. Liver disease in adults with alpha-1 -antitrypsin deficiency. N Engl J Med. 1972 Dec 21;287(25):1264–1267. doi: 10.1056/NEJM197212212872502. [DOI] [PubMed] [Google Scholar]
  2. Blobel G., Dobberstein B. Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J Cell Biol. 1975 Dec;67(3):835–851. doi: 10.1083/jcb.67.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carrell R. W., Jeppsson J. O., Laurell C. B., Brennan S. O., Owen M. C., Vaughan L., Boswell D. R. Structure and variation of human alpha 1-antitrypsin. Nature. 1982 Jul 22;298(5872):329–334. doi: 10.1038/298329a0. [DOI] [PubMed] [Google Scholar]
  4. Cox D. W., Huber O. Rheumatoid arthritis and alpha-1-antitrypsin. Lancet. 1976 Jun 5;1(7971):1216–1217. doi: 10.1016/s0140-6736(76)92163-2. [DOI] [PubMed] [Google Scholar]
  5. Eriksson S., Larsson C. Purification and partial characterization of pas-positive inclusion bodies from the liver in alpha 1-antitrypsin deficiency. N Engl J Med. 1975 Jan 23;292(4):176–180. doi: 10.1056/NEJM197501232920403. [DOI] [PubMed] [Google Scholar]
  6. Eriksson S. Studies in alpha 1-antitrypsin deficiency. Acta Med Scand Suppl. 1965;432:1–85. [PubMed] [Google Scholar]
  7. Galfre G., Howe S. C., Milstein C., Butcher G. W., Howard J. C. Antibodies to major histocompatibility antigens produced by hybrid cell lines. Nature. 1977 Apr 7;266(5602):550–552. doi: 10.1038/266550a0. [DOI] [PubMed] [Google Scholar]
  8. Goding J. W. Antibody production by hybridomas. J Immunol Methods. 1980;39(4):285–308. doi: 10.1016/0022-1759(80)90230-6. [DOI] [PubMed] [Google Scholar]
  9. Hartree E. F. Determination of protein: a modification of the Lowry method that gives a linear photometric response. Anal Biochem. 1972 Aug;48(2):422–427. doi: 10.1016/0003-2697(72)90094-2. [DOI] [PubMed] [Google Scholar]
  10. Hodges J. R., Millward-Sadler G. H., Barbatis C., Wright R. Heterozygous MZ alpha 1-antitrypsin deficiency in adults with chronic active hepatitis and cryptogenic cirrhosis. N Engl J Med. 1981 Mar 5;304(10):557–560. doi: 10.1056/NEJM198103053041001. [DOI] [PubMed] [Google Scholar]
  11. Jeppsson J. O. Amino acid substitution Glu leads to Lys alpha1-antitrypsin PiZ. FEBS Lett. 1976 Jun 1;65(2):195–197. doi: 10.1016/0014-5793(76)80478-4. [DOI] [PubMed] [Google Scholar]
  12. Larsson C., Eriksson S., Dirksen H. Smoking and intermediate alpha1-antitrypsin deficiency and lung function in middle-aged men. Br Med J. 1977 Oct 8;2(6092):922–925. doi: 10.1136/bmj.2.6092.922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lieberman J. Heterozygous and homozygous alpha-antitrypsin deficiency in patients with pulmonary emphysema. N Engl J Med. 1969 Aug 7;281(6):279–284. doi: 10.1056/NEJM196908072810601. [DOI] [PubMed] [Google Scholar]
  14. Morse J. O., Lebowitz M. D., Knudson R. J., Burrows B. Relation of protease inhibitor phenotypes to obstructive lung diseases in a community. N Engl J Med. 1977 May 26;296(21):1190–1194. doi: 10.1056/NEJM197705262962102. [DOI] [PubMed] [Google Scholar]
  15. Novis B. H., Young G. O., Bank S., Marks I. N. Chronic pancreatitis and alpha-1-antitrypsin. Lancet. 1975 Oct 18;2(7938):748–749. doi: 10.1016/s0140-6736(75)90728-x. [DOI] [PubMed] [Google Scholar]
  16. Pierce J. A., Jeppsson J. O., Laurell C. B. alpha-1 Antitrypsin phenotypes determined by isoelectric focusing of the cysteine-antitrypsin mixed disulfide in serum. Anal Biochem. 1976 Jul;74(1):227–241. doi: 10.1016/0003-2697(76)90327-4. [DOI] [PubMed] [Google Scholar]
  17. Rogers J., Kalsheker N., Wallis S., Speer A., Coutelle C. H., Woods D., Humphries S. E. The isolation of a clone for human alpha 1-antitrypsin and the detection of alpha 1-antitrypsin in mRNA from liver and leukocytes. Biochem Biophys Res Commun. 1983 Oct 31;116(2):375–382. doi: 10.1016/0006-291x(83)90532-6. [DOI] [PubMed] [Google Scholar]
  18. Shulman M., Wilde C. D., Köhler G. A better cell line for making hybridomas secreting specific antibodies. Nature. 1978 Nov 16;276(5685):269–270. doi: 10.1038/276269a0. [DOI] [PubMed] [Google Scholar]
  19. Vaughan L., Lorier M. A., Carrell R. W. alpha 1-Antitrypsin microheterogeneity. Isolation and physiological significance of isoforms. Biochim Biophys Acta. 1982 Mar 4;701(3):339–345. doi: 10.1016/0167-4838(82)90237-0. [DOI] [PubMed] [Google Scholar]

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