Brief Report: Prevalence of Antineutrophil Cytoplasmic Antibodies in Infective Endocarditis

Abstract

Objective. Infective endocarditis (IE) mimics primary systemic vasculitis, and there are sporadic reports of positivity for antineutrophil cytoplasmic antibodies (ANCAs) among patients with IE. Because the frequency of ANCAs in IE is unknown, this study was undertaken to assess the seroprevalence of ANCAs in a large number of patients with IE.Methods. The study was conducted in the framework of a single-center prospective cohort study of incident IE cases. Demographic, clinical, laboratory, and microbiologic data were collected, and magnetic resonance imaging of the brain was performed at diagnosis. For those patients whose serum had been stored at diagnosis, ANCAs were assessed by indirect immunofluorescence assay in ethanol-, formalin-, and methanol-fixed neutrophils. In addition, ANCA specificity for proteinase 3 (PR3) and myeloperoxidase (MPO) was assessed by enzyme-linked immunosorbent assay. Rheumatoid factor (RF), antinuclear antibodies (ANAs), anticardiolipin antibodies (aCL), and serum Ig levels were also measured. Comparisons between groups were made using Wilcoxon's rank sum and chi-square or Fisher's exact tests.Results. Among 109 patients with IE, 18% had cytoplasmic ANCAs (cANCA) and/or perinuclear ANCAs (pANCA) and 8% had PR3-ANCAs or MPOANCAs, some with very high titers. Positivity for both cANCA or pANCA and PR3-ANCAs or MPO-ANCAs was found in 6% of patients, and RF, ANAs, and aCL were detected in 35%, 16%, and 23% of samples, respectively. No consistent clinical pattern of IE was observed in the anti-PR3/anti-MPO-positive IE patients, whereas positivity for cANCA/pANCA was associated with younger age (P ‫؍‬ 0.022), more frequent occurrence of echocardiographic vegetations (P ‫؍‬ 0.043), and abovenormal serum IgG levels (P ‫؍‬ 0.017).Conclusion. ANCAs, including PR3-and MPOANCAs, occur in a substantial proportion of patients with IE. The link between cANCA/pANCA and specific features of IE requires further study.Antineutrophil cytoplasmic antibodies (ANCAs) target various constituents of human neutrophils. Indirect immunofluorescence assays can distinguish ANCAs with cytoplasmic (cANCA) or perinuclear (pANCA) staining patterns; the specific self-reactivities can be further characterized by enzyme-linked immunosorbent assay (ELISA). ANCAs are a major biomarker of ANCA-associated vasculitides (1), with up to 95% of patients showing positive serology results depending on the vasculitis type (2). Specifically, ANCAs directed against proteinase 3 (PR3) and myeloperoxidase (MPO) are highly predictive of ANCA-associated vasculitis, although MPO-ANCAs are also found in other autoimmune diseases and have been associated with infection or drug exposure (2-4). Sporadic case reports have described PR3-or MPO-ANCAs in patients with infective endocarditis (IE) (2,3,5-7). The production of non-organ-specific autoantibodies in IE is well established with regard to rheumatoid factor (RF), and findings in a single case series have suggested a similar relationship between IE and antinuclear antibodies (ANAs), anti...

Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis

“…Langlois et al 100 reported ANCAs by IIF in 12 out of 50 patients (24%) with infective endocarditis; four patients had PR3-ANCAs, one patient had MPO-ANCAs and two patients had both PR3-ANCAs and MPO-ANCAs. Mahr et al 101 reported ANCA by IIF in 20 out of 109 patients (18%) with infective endocarditis (14 patients were positive for C-ANCA and six were positive for P-ANCA); of these, three patients had C-ANCA and PR3-ANCAs, two patients had C-ANCA and MPOANCAs, one patient had P-ANCA and MPO-ANCAs, one patient had just PR3-ANCAs and one patient had just MPO-ANCAs. Misdiagnosis of sub-acute bacterial endocarditis as AAV and initiation of inappropriate immunosuppressive therapy can have devastating consequences 102 .…”

2015 ESC Guidelines for the management of infective endocarditis

“…Etiologia często jest wieloczynnikowa [296,297]: (i) kompleksy immunologiczne i naczyniowe kłębuszkowe zapalenie nerek; (ii) zawał nerki, głównie na skutek zatorów septycznych, występujący w dowolnym czasie w przebiegu IZW; (iii) pogorszenie funkcji hemodynamicznych w przypadku HF lub ciężkiej posocznicy albo w okresie pooperacyjnym; (iv) nefrotoksyczność antybiotyków (ostre śródmiąższowe zapalenie nerek), wyraźnie związane ze stosowaniem aminoglikozydów, wankomycyny (toksyczne działanie synergistyczne z aminoglikozydami), a nawet benzylopenicyliny w wysokich dawkach; (v) nefrotoksyczność środków kontrastowych stosowanych w diagnostyce obrazowej.…”

A case of aortic and mitral valve involvement in granulomatosis with polyangiitis

“…c-ANCA are most often encountered in SBE, but p-ANCA are also described. Recently, among 109 infective endocarditis cases, 18% had c-or p-ANCA, and 8% had anti-PR3 or anti-MPO [5]. This report illustrates a diagnostic difficulty between SBE and specific involvement of GPA with no classical systemic symptoms.…”

“…In the present report, blood cultures were negative and p-ANCA anti-MPO positive. However, this type of valvular involvement associated with ANCA may be encountered in SBE [5]. c-ANCA are most often encountered in SBE, but p-ANCA are also described.…”