Immunohistochemical and genetic characterization of the M Cagliari α-1- antitrypsin molecule (M-like α-1-antitrypsin deficiency)

C. Sergi, G. G. Consalez, G. Fabbretti, M. Brisigotti, G. Faa, V. Costa, G. Romeo, F. Callea

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Genetic α-1-antitrypsin (AAT) deficiency may be due to defective secretion, intracellular degradation, or lack of synthesis. Defective secretion results in hepatocytic storage and liver disease. These two events occur only with the common deficiency variant, Z AAT, and with a few rare deficiency variants, called M-like. Hepatocytic storage of AAT (either Z or M-like) can be demonstrated in tissue sections by specific immunostaining with a polyclonal anti-AAT antibody, that recognizes all variants of AAT. A monoclonal antibody capable of selectively and exclusively reacting with Z AAT has been generated and successfully used in both serum and tissue studies. EXPERIMENTAL DESIGN: To determine whether a new M-like variant, M Cagliari, carries a mutation different from Z AAT, we have compared antigenic properties and DNA sequences of the two variants. Liver tissue sections from PiZ and PiM Cagliari patients were stained with both polyclonal anti-AAT and monoclonal anti-Z AAT antibodies. DNAs were polymerase chain reaction-amplified with AAT-specific primers and sequenced. RESULTS: Liver tissue sections from PiZ livers were positively stained with either the polyclonal or the monoclonal antibody. The PiM Cagliari liver sections reacted with the polyclonal antibody, but not with the monoclonal anti-Z AAT, thus indicating a difference in antigenicity from Z AAT. Accordingly, DNA analysis ruled out a Z mutation and revealed a microdeletion in exon II, identical with M Malton. CONCLUSIONS: A simple immunohistochemical assay based upon the application of both polyclonal and monoclonal antibodies represents a reliable test to distinguish Z and nonZ AAT deficiencies, thus assisting in the selection of cases worthy of more time-consuming analyses such as DNA sequencing. The same approach may be used for the characterization of as yet undefined PiM cases with AAT liver storage.

Original languageEnglish
Pages (from-to)130-133
Number of pages4
JournalLaboratory Investigation
Issue number1
Publication statusPublished - 1994


  • Genetic variants
  • Immunohistochemistry
  • M Cagliari
  • Phe deletion

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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