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- Elzouki, A N, et al.
(author)
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Is there a relationship between abdominal aortic aneurysms and alpha1-antitrypsin deficiency (PiZ)?
- 1999
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In: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1532-2165 .- 1078-5884. ; 17:2, s. 149-154
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine if the frequency of alpha 1AT deficiency (PiZ) is increased in patients with abdominal aortic aneurysm (AAA), and, to investigate whether aneurysmal stiffness and other clinical characteristics differ in AAA patients with and without alpha 1AT deficiency. METHODS: We identified alpha 1AT-deficient individuals by a monoclonal-antibody ELISA technique, in 102 consecutive patients with AAA. Positive ELISA samples were further phenotyped by isoelectric focusing to differentiate between the heterozygosity (PiZ) and homozygosity (PiZZ) state. Aneurysmal diameter and stiffness was measured using echotracking sonography and blood pressure measurements. RESULTS: The frequency of heterozygous alpha 1AT deficiency (PiZ) in patients with AAA was similar to that in the general population (6.8% and 4.7%, respectively, p > 0.3). The frequency of popliteal and femoral aneurysm was similar in male PiZ-carriers and non-carriers with AAA, as were age at diagnosis of AAA, aneurysmal diameter, aneurysmal stiffness, and presence of factors that may be associated with AAA (i.e. smoking, hypertension, diabetes mellitus, and family history of AAA). Occurrence of ischaemic heart disease was more frequent in male non-PiZ-carriers than in male PiZ-carriers with AAA (p = 0.03). CONCLUSIONS: The frequency of alpha 1AT deficiency (PiZ) was not increased in our series of patients with AAA and patients in whom the two disorders coexisted did not appear to have different clinical characteristics except for the lower occurrence of ischaemic heart disease among the PiZ-carriers.
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| 2. |
- ELZOUKI, A.-N., et al.
(author)
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Strong link between the alpha1‐antitrypsin PiZ allele and Wegener's granulomatosis
- 1994
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 236:5, s. 543-548
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Journal article (peer-reviewed)abstract
- Abstract. Objectives. To ascertain whether a relationship exists between the PiZ alpha1‐antitrypsin (α1AT) variant and antineutrophil cytoplasm antibodies (ANCA)‐positive vasculitis in a large group of Swedish patients, and whether analysis for the presence of the PiZ variant might be useful for diagnostic or prognostic purposes. Design. Retrospective cross‐sectional study. Setting. The Department of Internal Medicine, Malmö General Hospital, and the Department of Nephrology, University of Lund, Sweden. Subjects and main outcome measures. Serum samples from 105 proteinase 3‐ANCA‐positive patients were analysed using an elisa with a monoclonal antibody specific for the PiZ‐gene product. Complete clinical data were retrieved for 84% (88/105) of the patients, for diagnosis and survival analysis. Results. We identified 17 heterozygotes and one homozygote (P < 0.0001). All 88 patients with available clinical data were considered to have some form of microscopic vasculitis including 66 (75%) diagnosed as having Wegener's granulomatosis (WG), of whom 15 (23%) were PiZ heterozygotes (odds ratio 6.0, 95% confidence interval 3–10). There were no significant differences between PiZ carriers and noncarriers in sex distribution, mean age at onset of disease, interval between onset and inclusion in the study, or in median duration of follow‐up (P > 0.2 for all comparisons). During follow‐up, 38% (6/16) of the PiZ heterozygotes died, compared with 17% (11/66) of noncarriers of the variant (P = 0.02), which suggests that PiZ heterozygosity may be a marker of poor prognosis. PiZ heterozygotes with systemic vasculitis would not appear to be identifiable by their pretreatment plasma α1AT concentrations, as all such patients in the present study had concentrations within or above the normal range. Conclusion. We conclude that heterozygotes for the PiZ variant of the α1AT gene are at greater risk of than the general population of developing WG. Knowledge of such a genetic factor may not only aid our understanding of the mechanism involved in this illness but may also serve as significant prognostic factor in following the course of the disease. 1994 Blackwell Publishing Ltd
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| 3. |
- Mazodier, P., et al.
(author)
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Systemic necrotizing vasculitides in severe alpha1-antitrypsin deficiency
- 1996
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In: QJM - Monthly Journal of the Association of Physicians. - : Oxford University Press (OUP). - 0033-5622. ; 89:8, s. 599-611
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Journal article (peer-reviewed)abstract
- We describe the clinical presentation and outcome in a series of eight patients with systemic necrotizing vasculitis and severe alpha1-antitrypsin (AAT) deficiency followed up at three Swedish hospitals during 1968-92. We also review six other cases reported in the literature during the same period. Diagnosis of severe AAT deficiency was based on the presence of the PiZZ phenotype, or low plasma total trypsin inhibitory capacity, or a low plasma AAT concentration (10-40% of the normal mean value) and presence of the PiSZ- or PiFZ phenotype. The diagnosis of systemic vasculitis was biopsy-verified in all eight patients. Pretreatment laboratory findings, treatment protocol, and outcome were reviewed in each of the 14 patients. Of the eight patients in the Swedish series, six had systemic vasculitis of the microscopic polyangiitis form, one had Wegener's granulomatosis, and another had Henoch-Schonlein purpura. In the series as a whole (n = 14), median age at diagnosis was 48 years (range 44-84), the median number of affected organs was eight, and all 14 patients had skin involvement, and either renal or joint involvement (in most cases both); 71% (10/14) had emphysema; 57% (8/14) had hepatic abnormalities (two having cirrhosis, two fibrosis, and one multiple aneurysms in hepatic arteries); one patient who presented with acute ulcerative colitis developed manifest vasculitic syndrome three years later; and 64% (9/14) died, the major cause of death being renal failure. This syndrome, characterized by multiple organ involvement and fatal outcome, has been underdiagnosed. Physicians should be alert to the presence of the PiZ AAT deficiency gene in patients with systemic vasculitis, especially when the course is progressive or when the patient also has emphysema or cirrhosis. Awareness of those features may aid prompt recognition and enable early treatment.
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