Antibodies to neutrophil granulocyte myeloperoxidase and elastase: autoimmune responses in glomerulonephritis due to hydralazine treatment

Abstract

Autoantibodies against myeloperoxidase and elastase were found in a study of nine patients who had developed glomerulonephritis after treatment with hydralazine, but not in patients who were treated with hydralazine without side-effects. Circulating IgM isotype antibodies against myeloperoxidase, and IgM and IgG anti-elastase, were mainly present during the initial months after withdrawal of the drug. By contrast, IgG isotype antibodies against myeloperoxidase, initially found in seven patients, had increased in concentration and were present in all patients at follow-up after 4-12 years.

Outcomes of hydralazine induced renal vasculitis

“…Withdrawal of hydralazine Reports of rapidly progressive renal failure in patients taking hydralazine were initially reported in the 1980s (4,7,11). The association of ANCA with glomerulonephritis was first described in 1991; in this report, nine patients with hydralazine-induced glomerulonephritis were found to have antibodies to myeloperoxidase and elastase (8). Since this initial report, several case reports and case series have described vasculitis in patients taking hydralazine.…”

“…Hydralazine-induced vasculitis involving the skin was first reported in 1980, and vasculitis involving the kidneys was first suspected in 1981 (5,6). Cases of rapidly progressive glomerulonephritis were reported in 1983, and subsequently, ANCA positivity was demonstrated in some of these cases (7,8). While the cessation of hydralazine therapy helps non-organ-threatening manifestations of hydralazine-induced vasculitis, the renal outcomes of these patients are not clear.…”

Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients with hyperthyroidism treated with antithyroid drugs: A long‐term followup study

“…Certain drugs have been linked to the induction of ANCA and the onset of ANCA-associated vasculitis (AAV) (10). There are several case reports implicating hydralazine (11)(12)(13)(14) and propylthiouracil (PTU) (15)(16)(17)(18)(19) in the induction of AAV. Occasionally, other drugs are mentioned, including other antithyroid drugs, such as carbimazole (17) and methimazole (20,21).…”

Studies of epitope restriction on myeloperoxidase (MPO), an important antigen in systemic vasculitis

“…First, pairs of sera or affinity-purified IgG were coincubated. A total of 12 affinity-purified preparations were used (patients [1][2][3][4][5][6][7][8][9][10][11][12]. In further studies the affinity-purified IgG samples were also each co-incubated with the mouse anti-MPO monoclonal (MPO-7) or with the rabbit polyclonal anti-MPO antibody.…”

“…The technology has already proved to be very useful in the fields of antigen-antibody interactions, epitope mapping, receptor-ligand interactions with respect to the T cell receptor, as well as hormone-receptor relationships in many endocrine systems, DNA-DNA and DNA-RNA interactions, and is of increasing value in the evaluation of the pharmacokinetics of small and large drug molecules. drugs such as hydralazine [7] together with the therapeutic options available [8] might be enhanced by a better understanding of the underlying molecular mechanisms. To examine further the association of these antibodies with disease, we decided to investigate the epitopes recognized on MPO by anti-MPO antibodies.…”