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Alpha 1-antitrypsin activity is markedly decreased in Wegener’s granulomatosis

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Abstract

Alpha 1-antitrypsin (A1AT) is the most abundant proteinase inhibitor in plasma and the main inhibitor of Proteinase 3, the target antigen of antineutrophil cytoplasmic antibodies (ANCAs) that predominant in Wegeners’ granulomatosis. Α1AT deficiency correlated with ANCA-associated vasculitis. This study explores the trypsin inhibitory capacity (TIC), specific activity, and phenotypic deficiency of Α1AT in Wegener’s granulomatosis. Twenty-seven WG patients were studied. ANCA was tested by IIF and ELISA. Serum a1-anti-trypsin levels were quantified in WG patients and healthy controls by immunoturbidimetric assay. Serum TIC was assessed by the enzymatic colorimetric assay. Phenotypes of A1AT were detected by Isoelectric Focusing. A1AT concentration was equivalent in patients and controls; however, serum TIC (P = 0.001) and specific activity of A1AT (P = 0.001) were dramatically lower in WG patients. Five patients had deficient phenotypes of A1AT: MZ (n = 3), MS (n = 1) and SS (n = 1). This was correlated with an increase in the prevalence of deficient phenotypes of A1AT in WG (P = 0.01). Trypsin inhibitory capacity and specific activity of A1AT were decreased in WG patients and may be involve in disease pathogenesis and can worsen the clinical manifestations. This A1AT deficiency probably resulted from oxidative inactivation and/or enzymatic degradation of A1AT. This could result in localized deficiency of A1AT in vessel wall interfaces and lead to severe disease.

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Acknowledgments

We would like to thank Rheumatology Research Center for technical assistance. This study was supported by Tarbiat Modares University.

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The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Ali Mota, Abbas Sahebghadam Lotfi & Saeed Najavand

  2. Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Ahmad-Reza Jamshidi

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  1. Ali Mota
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  2. Abbas Sahebghadam Lotfi
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  4. Saeed Najavand
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Correspondence to Abbas Sahebghadam Lotfi.

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Mota, A., Sahebghadam Lotfi, A., Jamshidi, AR. et al. Alpha 1-antitrypsin activity is markedly decreased in Wegener’s granulomatosis. Rheumatol Int 34, 553–558 (2014). https://doi.org/10.1007/s00296-013-2745-9

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  • DOI: https://doi.org/10.1007/s00296-013-2745-9

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