Sequential development of perinuclear ANCA-associated vasculitis and anti-glomerular basement membrane glomerulonephritis

Antigen and Epitope Specificity of Anti–Glomerular Basement Membrane Antibodies in Patients with Goodpasture Disease with or without Anti-Neutrophil Cytoplasmic Antibodies

“…Some reports show that anti-GBM antibodies appear a few months after the (10,27). It was presumed that ANCAassociated conditions might be the initial and underlying disease (10,16); a possible approach was that ANCA-associated damage to GBM might uncover the "hidden antigens," ␣3(IV)NC1 or other components, from the GBM, inducing the formation of antibodies to GBM, but some reports described the opposite sequence of events (28,29), which is hard to explain by this hypothesis.…”

“…Then chimeric molecules of human ␣3(IV)NC1 and ␣1(IV)NC1 expressed in a mammalian cell line were used for epitope mapping (6 -9). Hellmark et al (8) identified nine critical amino acid residues in the amino-terminal part of the ␣3(IV)NC1 sequence (positions 17,18,19,21,24,27,28,31, and 57) and produced a recombinant construct named S2 that expresses these substitutions in the ␣1(IV) background (8). In other studies, two regions that harbor conformational anti-GBM epitopes had been defined at residues 17 to 31 and 127 to 141 of the ␣3(IV)NC1 domain, which were named as E A and E B , respectively (7).…”

A case of PR3–ANCA-positive anti-GBM disease associated with intrarenal arteritis and thrombotic microangiopathy

“…First, susceptible age of ''double positive'' disease is greater than ''pure'' anti-GBM disease, resembling ANCA-associated vasculitis [5][6][7][8][9]. This feature is proposed as sequential sensitization of GBM antigen following glomerular basement membrane destruction via ANCA-associated vasculitis, and the hypothesis is supported by cases showing positive conversion of anti-GBM antibody following ANCA-associated vasculitis [5,8,[20][21][22]. Second, ''double positive'' disease has a higher risk of relapse than ''pure'' anti-GBM disease [1,8,11].…”

“…Taken together, the renal PR3-ANCA-associated vasculitis might precede and subsequently develop pulmonary-renal syndrome via anti-GBM antibody in the present case. While MPO-ANCAassociated vasculitis are the majority of glomerular disease preceding anti-GBM disease, IgA nephritis [20], membranous nephropathy [20], and PR3-ANCA-associated vasculitis [15] cases are also reported to precede anti-GBM disease. Moreover, subclinical elevations of MPO-ANCA and PR3-ANCA titer are reported to evoke anti-GBM disease [27].…”

“…Some MPO-ANCA-positive cases reveal intrarenal arteritis, which is histological observation theoretically specific for ANCA in ''double positive'' disease [19,20]. In contrast, as far as we know, none of the PR3-ANCA-positive ''double positive'' disease has been reported with kidney biopsy-proven arteritis.…”