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Serum protease inhibitory capacity

Recent knowledge on α1-antitrypsin deficiency

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Ricerca in clinica e in laboratorio

Summary

The molecular structure and the serum levels of α1-antitrypsin, the major antiprotease of human serum, are controlled by a series of codominant alleles at a single chromosomal locus, known as the Pi (protease-inhibitor) locus. The congenital deficiency of this inhibitor is known to be associated with the development of lung emphysema in early adulthood and chronic liver disease in childhood. Less frequent associations have been reported, such as rheumatoid arthritis, membranoproliferative glomerulonephritis and mosaicism for sex chromosomes. The identification of several suballeles of the Pi system, which was accomplished by means of a refinement of the isoelectric focusing technique, has promoted research concerning their possible pathogenic implications. The studies so far performed have often led to contradictory results, but nevertheless they strongly ascribe the property of controlling the quantitative levels of α1-antitrypsin to certain M subtypes. Intermediate M3 subtype has recently been associated with the development of chronic obstructive lung disease in adulthood. Should this finding be confirmed by further evidence, a new approach to the prevention of lung disease could be considered, given that 30% of the individuals are carriers of the M3 suballele. In Italy, the incidence of congenital deficiency of α1-antitrypsin appears to be greater in the northern regions, where 15–20 out of every 100,000 individuals are affected by the severe (ZZ) form of the deficiency.

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References

  1. Allen R. C., Harley R. A., Talamo R. C.: A new method for the determination of α1-antitrypsin phenotype using isoelectric focusing on polyacrylamide gel slabs — Amer. J. Path.62, 732, 1974.

    CAS  Google Scholar 

  2. Arnaud P., Burdash N. M., Wilson G. B., Fudenberg H. H.: Alpha-1-antitrypsin (Pi) types in Down’s syndrome — Clin. Genet.10, 239, 1976.

    PubMed  CAS  Google Scholar 

  3. Arnaud P., Galbraith R. M., Faulk W., Black C., Hughes G. V.: Alpha-1-antitrypsin in adult rheumatoid arthritis — Lanceti, 1236, 1979.

    Article  Google Scholar 

  4. Auconi P., Biagini R., Donnini R., Fabiano A., Ragusa A., Massi G.: Diagnosi neonatale di delezione parziale di un allele Pi (genotipo S−) — Riv. ital. Pediat.7, 257, 1981.

    Google Scholar 

  5. Bencze K., Sacke L., Fruhman L.: PiM subtypes: do they play a role in development of chronic obstructive pulmonary disease? — Chest77, 761, 1980.

    Article  PubMed  CAS  Google Scholar 

  6. Camus L., Gley E.: Action du sérum sanguin sur quelques ferments digestifs — C.R. Soc. Biol. (Paris)49, 875, 1897.

    Google Scholar 

  7. Charlionet R., Martin J.-P., Sesboué R., Ropartz C.: Is there a relationship between alpha-1-antitrypsin PiMZ phenotype and hepatic hepatoma? — Biomedicine25, 125, 1976.

    PubMed  CAS  Google Scholar 

  8. Charlionet R., Sesboué R., Morcamp C., Lefebvre F., Martin J.-P.: Genetic variants of serum alpha-1-antitrypsin (Pi types) in Normans — Hum. Hered.31, 104, 1981.

    Article  PubMed  CAS  Google Scholar 

  9. Constants J., Viau M., Gouillard C.: PiM4: an additional PiM subtype — Hum. Genet.55, 119, 1980.

    Article  Google Scholar 

  10. De Montis G., Martin J.-P.: États allergiques de l’enfant: rôle des sous-types PiM de l’alpha-1-antitrypsine — Nouv. Presse méd.44, 3875, 1979.

    Google Scholar 

  11. Di Nardo C., Sabatino G., Bucci E., Midulla C., Mancinelli R., Midulla M.: Serum alpha-1-antitrypsin in children with bronchitis — Lanceti, 1216, 1978.

    Google Scholar 

  12. Eriksson S., Hagerstrand I.: Cirrhosis and malignant hepatoma in α1-antitrypsin deficiency — Acta med. scand.195, 451, 1974.

    PubMed  CAS  Google Scholar 

  13. Gadek J., Keogh B., Crystal R. G.: Opportunities for the specific therapy of destructive lung disease — Bull. europ. Physiopath. resp.16 (Suppl.), 389, 1980.

    Google Scholar 

  14. Hadchouel M., Gautier M.: Histologic study of the liver in the early cholestatic phase of α1-antitrypsin deficiency — J. Pediat.89, 211, 1976.

    Article  PubMed  CAS  Google Scholar 

  15. Harada S., Miyake K., Suzuki H., Oda T.: New phenotypes of serum α1-antitrypsin in Japanese detected by gel slab isoelectric focusing — Hum. Genet.38, 333, 1977.

    Article  PubMed  CAS  Google Scholar 

  16. Hodges H., Millward G., Barbatis C., Wright R.: Heterozygous MZ α1-antitrypsin deficiency in adults with chronic active hepatitis and cryptogenetic cirrhosis — New Engl. J. Med.304, 557, 1981.

    PubMed  CAS  Google Scholar 

  17. Hood J., Koep L., Peters R.: Liver transplantation for advanced liver disease with α1-antitrypsin deficiency — New Engl. J. Med.302, 275, 1980.

    Google Scholar 

  18. Jeppsson J.-O.: Amino acid substitution Glu-Lys in α1-antitrypsin PiZ —Febs Letter65, 195, 1976.

    Article  CAS  Google Scholar 

  19. Jeppsson J.-O., Cordensius E., Gustavii B., Sveger T.: Prenatal diagnosis of α1-antitrypsin deficiency by analysis of fetal blood obtained at fetoscopy — Pediat. Res.15, 254, 1981.

    Article  PubMed  CAS  Google Scholar 

  20. Klasen E. C., D’Andrea F., Bernini L. F.: Phenotype and gene distribution of α1-antitrypsin in a North-Italian population — Hum. Hered.28, 474, 1978.

    Article  PubMed  CAS  Google Scholar 

  21. Larson C., Eriksson S., Dirksen M.: Smoking and intermediate α1-antitrypsin deficiency and lung function in middle aged men — Brit. med. J.ii, 922, 1977.

    Google Scholar 

  22. Laurell C.-B., Eriksson S.: The electrophoretic α1-globulin pattern of serum α1-antitrypsin deficiency — Scand. J. clin. Lab. Invest.15, 132, 1963.

    Article  CAS  Google Scholar 

  23. Martin J.-P.: Further examples confirming the existence of Pi-null (Pi− — Path. et Biol.23, 521, 1975.

    CAS  Google Scholar 

  24. Massi G., Auconi P.: Unpublished data.

  25. Massi G., Cotumaccio R., Auconi P., Patriarchi P., Mirabella A., Rizzo G.: PiM subtypes in COPD — Chest 1982. (In press).

  26. Massi G., Fabiano A., Ragusa D., Auconi P.: Characterization of α1-antitrypsin by isoelectric focusing on ultrathin polyacrylamide gel layer — Hum. Genet.53, 91, 1979.

    Article  PubMed  CAS  Google Scholar 

  27. Massi G., Fabiano A., Ragusa D., Auconi P., Biagini R., Farinato M. A., Bandelloni R.: Alpha-1-antitrypsin phenotypes and PiM subtypes in Italy — Bull. europ. Physiopath. resp.16 (Suppl.), 301, 1980.

    Google Scholar 

  28. McDonagh D. J., Nathan S. P., Knudson R. J., Lebowitz M. D.: Assessment of alpha-1-antitrypsin deficiency heterozygosity as a risk factor in the etiology of emphysema — J. clin. Invest.63, 299, 1979.

    Article  PubMed  CAS  Google Scholar 

  29. Mittman C.: The PiMZ phenotype: is it a significant risk factor for the development of chronic obstructive lung disease? — Amer. Rev. resp. Dis.118, 649, 1978.

    PubMed  CAS  Google Scholar 

  30. Miyake K., Oka N., Oda T., Harada S.: Distribution of alpha-1-antitrypsin phenotypes in Japanese: description of PiM subtypes by isoelectric focusing — Jap. J. hum. Genet.24, 55, 1979.

    Article  CAS  Google Scholar 

  31. Moroz S., Cutz E., Balfe W., Sass-Kortass A.: Membranoproliferative glomerulonephritis in childhood cirrhosis associated with α1-antitrypsin deficiency — Pediatrics57, 232, 1976.

    PubMed  CAS  Google Scholar 

  32. Morse J. O.: Medical progress: α1-antitrypsin deficiency. I. — New Engl. J. Med.299, 1045, 1978.

    PubMed  CAS  Google Scholar 

  33. Morse J. O.: Medical progress: α1-antitrypsin deficiency. II. — New Engl. J. Med.299, 1045, 1978.

    PubMed  CAS  Google Scholar 

  34. Musiani P., Tomasi B.: Isolation, chemical and physical properties of α1-antitrypsin — Biochemistry15, 798, 1976.

    Article  PubMed  CAS  Google Scholar 

  35. Odievre M., Martin J.-P., Hadchouel M., Alagille D.: Alpha-1-antitrypsin deficiency and liver disease in children: phenotypes manifestation and prognosis — Pediatrics57, 226, 1976.

    PubMed  CAS  Google Scholar 

  36. Owen M. C., Carrell R. W.: Alpha-1-antitrypsin: molecular abnormality of S variant — Brit. med. J.i, 131, 1976.

    Google Scholar 

  37. Piantelli N., Auconi P., Musiani P.: Alpha-1-antitrypsin phenotypes in newborns from Central and Southern Italy — Hum. Hered.28, 468, 1978.

    Article  PubMed  CAS  Google Scholar 

  38. Reintoft I., Hagerstrand I.: Alpha-1AT and hepatoma. Does the Z gene variant of alpha-1-antitrypsin predispose to hepatic carcinoma? — Hum. Path.10, 419, 1979.

    Article  PubMed  CAS  Google Scholar 

  39. Schumacher G.: Alpha-1-antitrypsin in genital secretions — J. reprod. Med.5, 13, 1970.

    Google Scholar 

  40. Schyldower M., Waxman S., Patterson P.: Coexistence of deficiency in alpha-1-anti-trypsin and growth hormone — New Engl. J. Med.300, 366, 1979.

    Google Scholar 

  41. Sharp H. L.: The current status of α1-antitrypsin, a protease inhibitor, in gastrointestinal disease — Gastroenterology70, 611, 1976.

    PubMed  CAS  Google Scholar 

  42. Sharp H. L., Bridges R. A., Krivit W., Freier E. F.: Cirrhosis associated with α1-antitrypsin deficiency: a previously unrecognized inherited disorder — J. Lab. clin. Med.73, 934, 1969.

    PubMed  CAS  Google Scholar 

  43. Sizaret P., Clerc M., Esteve J., Frants R. R., Billot J.: M2 alpha-1-antitrypsin phenotype and primary liver cancer — Brit. J. Cancer226, 228, 1981.

    Google Scholar 

  44. Sveger T.: Liver disease in alpha-1-antitrypsin deficiency detected by screening of 200,000 infants — New Engl. J. Med.294, 1316, 1976.

    PubMed  CAS  Google Scholar 

  45. Thompson W., Boyd S., McCoy A., Home C.: Serum protein changes associated with alpha-1-antitrypsin deficiency — Biomedicine29, 124, 1978.

    PubMed  CAS  Google Scholar 

  46. Vance J., Hall W., Schwartz R., Hyde R., Roghmann R., Mudholkar G.: Heterozygous alpha-1-antitrypsin deficiency and respiratory function in children — Pediatrics60, 763, 1977.

    Google Scholar 

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Authors and Affiliations

  1. Istituto di Anatomia e Istologia Patologica, Università Cattolica del Sacro Cuore, Roma

    Guido Massi

  2. Divisione di Pediatria, Ospedale Generale Provinciale di Arezzo, Via Curtatone 54, 52100, Arezzo, Italia

    Giovannella Bruscalupi & Pietro Auconi

Authors
  1. Guido Massi
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  2. Giovannella Bruscalupi
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  3. Pietro Auconi
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Massi, G., Bruscalupi, G. & Auconi, P. Serum protease inhibitory capacity. La Ricerca Clin. Lab. 12, 449–458 (1982). https://doi.org/10.1007/BF02909396

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  • DOI: https://doi.org/10.1007/BF02909396

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