Alpha-1 antitrypsin deficiency alleles and severe cystic fibrosis lung disease
a Respiratory Medicine Unit, Department of Medicine and
Department of Haematology, University of Cambridge, Cambridge, UK, b Department of Pathology, c Adult Cystic Fibrosis Unit, d Papworth Hospital, Cambridge, UK
Correspondence to: Dr R Mahadeva, Department of Haematology, University of Cambridge, MRC Centre, Hills Road, Cambridge CB2 2QH, UK.
Received 11 March 1998; Returned to authors 14 May 1998; Revised version received 8 July 1998; Accepted for publication 10 July 1998
BACKGROUND
Alpha-1 antitrypsin
(
1-AT) is the most abundant proteinase inhibitor
within the lung. We have recently reported the surprising observation
that cystic fibrosis patients with mild to moderate deficiency of
1-antitrypsin have significantly better pulmonary function than non-deficient patients. This study may have been biased
as it did not include the most severely affected patients who have died
in childhood or those who have undergone orthotopic lung
transplantation. The prevalence of 1-antitrypsin
deficiency alleles in this most severely affected group of patients
with cystic fibrosis was therefore assessed.
METHODSDNA was obtained from neonatal blood spots
from children with cystic fibrosis who had died from pulmonary disease
and from formalin fixed lung tissue from transplanted cystic fibrosis
patients. The common S and Z deficiency alleles of 1-AT
were sought by amplification mutagenesis of the appropriate region of
the 1-AT gene followed by restriction enzyme digestion
with Xmn I and Taq I, respectively.
RESULTSSeventy nine patients were identified
(seven dead, 72 transplanted). Two patients (2.5%) were heterozygous
for the Z allele of 1-AT and four (5.1%) were
heterozygous for the S allele. This is not significantly different from
the incidence in the normal population of 4% and 8% for the S and Z
alleles, respectively.
CONCLUSIONSThese data support previous findings
that deficiency of 1-AT is not associated with more
severe pulmonary disease in cystic fibrosis and may be associated with
milder lung disease. Further work is needed to clarify the mechanisms
underlying the progressive lung damage in cystic fibrosis.
1-antitrypsin;
cystic fibrosis;
1-proteinase inhibitor;
serpins;
bronchiectasis
© 1998 by Thorax
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