Open Accessα 1 ‐Antitrypsin deficiency and anti‐proteinase 3 antibodies in anti‐neutrophil cytoplasmic antibody (ANCA)‐associated systemic vasculitis
Author(s) -
SAVIGE J. A.,
CHANG L.,
COOK L.,
BURDON J.,
DASKALAKIS M.,
DOERYf J.
Publication year - 1995
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1995.tb03652.x
Subject(s) - antibody , proteinase 3 , immunology , autoantibody , anti neutrophil cytoplasmic antibody , myeloperoxidase , medicine , population , neutrophil elastase , phenotype , antigen , elastase , vasculitis , biology , inflammation , enzyme , disease , biochemistry , environmental health , gene
SUMMARY α 1 ‐antitrypsin (α 1 ‐AT) is a naturally occurring inhibitor of proteinase 3 (PR3) and elastase, two of the target antigens of anti‐neutrophil cytoplasmic antibodies (ANCA). An increased incidence of α 1 ‐AT phenotypes associated with dysfunctional α 1 ‐AT or low serum levels has been reported in patients with anti‐PR3 antibodies. We have studied the relationship between ANCA, and phenotypes and serum levels of α 1 ‐AT. Phenotypes usually associated with a moderate or severe reduction in α 1 ‐AT serum levels or in dysfunctional activity were found more often in individuals with anti‐PR3 antibodies than in the general population: four of the 31 patients (13%) with anti‐PR3 antibodies had phenotypes MZ ( n = 2), S ( n = 1) or Z ( n = 1) ( P < 0·05). However, the corresponding α 1 ‐AT serum levels were normal ( n = 3) or elevated ( n = 1). None of the 31 sera with anti‐PR3 antibodies had low levels of α 1 ‐AT. No abnormal α 1 ‐AT phenotype was demonstrated in seven patients with anti‐elastase antibodies, despite a low level of α 1 ‐AT in one serum. Anti‐myeloperoxidase antibodies are common in patients with ANCA, but no abnormal phenotype or low serum oi‐AT level was demonstrated in any of 29 sera containing these antibodies. Finally anti‐glomerular basement membrane (GBM) antibodies occur occasionally in patients with ANCA‐associated diseases, but again none of 10 sera had an abnormal α 1 ‐AT phenotype or low serum level. ANCA were not demonstrated by indirect immunofluorescence in any serum from 73 patients with abnormal α 1 ‐AT phenotypes. These results confirm that patients with anti‐PR3 antibodies often have α 1 ‐AT phenotypes that are usually associated with low serum levels of α 1 ‐AT or with dysfunctional protein. Nevertheless, the incidence of anti‐PR3 antibodies in patients with abnormal α 1 ‐AT phenotypes is very low. This probably reflects the rarity of Wegener's granulomatosis, the major disease associated with anti‐PR3 antibodies, and the relative frequency of abnormal α 1 ‐AT phenotypes. The mechanism for the development of anti‐PR3 antibodies in patients with abnormal α 1 ‐AT phenotypes is not clear, but may relate to the increased propensity of unbound and uninhibited PR3 to stimulate autoantibody production.