Two Cases of Proteinase 3-Anti-Neutrophil Cytoplasmic Antibody (PR3-ANCA)-related Nephritis in Infectious Endocarditis.

We herein report two cases of proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA)-related nephritis in infectious endocarditis. In both cases, the patients were middle-aged men with proteinuria and hematuria, hypoalbuminemia, decreased kidney function, anemia, elevated C-reactive protein (CRP) levels, and PR3-ANCA positivity. Each had bacteremia, due to Enterococcus faecium in one and Streptococcus bovis in the other. One patient received aortic valve replacement therapy for aortic regurgitation with vegetation, and the other underwent tricuspid valve replacement therapy and closure of a ventricular septic defect to treat tricuspid regurgitation with vegetation. These patients' urinary abnormalities and PR3-ANCA titers improved at 6 months after surgery following antibiotic treatment without steroid therapy.

Rapidly progressive glomerulonephritis associated with PR3-ANCA positive subacute bacterial endocarditis.

Patients with bacterial endocarditis often have renal complications. This report presents the case of an elderly man with rapidly progressive glomerulonephritis (RPGN) associated with subacute bacterial endocarditis (SBE) due to Enterococcus faecalis infection. The patient was positive for anti-proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) and rheumatoid factor (RF) with hypocomplementemia. Treatment for SBE with antibiotics and the surgical replacement of the affected valves resulted in an improvement of RPGN, the disappearance of PR3-ANCA and RF, and the normalization of hypocomplementemia. This rare case suggests the importance of recognizing the cause of positive PR3-ANCA, because SBE could be an occult cause of RPGN mimicking ANCA-associated vasculitis.

Three cases of PR3-ANCA positive subacute endocarditis caused by attenuated bacteria (Propionibacterium, Gemella, and Bartonella) complicated with kidney injury.

Subacute bacterial endocarditis (SBE) associated with antiproteinase-3 antineutrophil cytoplasmic antibodies (PR3-ANCA) has previously been reported in 10 cases of Streptococcus viridans and in 1 case of Escherichia faecalis infection. Most of these patients had hypocomplementemia and were positive for several autoantibodies. The infections in most of these patients showed good responses to antibiotic treatment. We report three patients with ANCA-positive SBE, which was induced by attenuated slow-growing intracellular pathogens; these patients had severe complications, such as acute kidney injury, cerebral embolism, and aortic valve destruction.

A case of mistaken identity: subacute bacterial endocarditis associated with p-antineutrophil cytoplasmic antibody.

Seventeen cases of subacute bacterial endocarditis (SBE) associated with antineutrophil cytoplasmic antibody (ANCA) have been reported. Fifteen such cases have been associated with c-ANCA postivity and two with dual p-ANCA and c-ANCA antibodies. The authors describe a 61-year-old man with sole p-ANCA positive autoantibodies on immunofluorescence presenting with Staphylococcus aureus SBE of the aortic valve. To the best of our knowledge this is the only reported case of sole p-ANCA positive SBE. Full recovery was achieved with antibiotic treatment. ANCAs are known to be associated with infection and their characterisation in acute illness is key in differentiating a true vasculitis from an infection. Unnecessary immunosuppression can be prevented with full investigation of such patients, including both immunofluorescence and ELISA.

Endocarditis associated with antineutrophil cytoplasmic antibodies: a case report and review of the literature.

We report a case of subacute bacterial endocarditis associated with small vessel vasculitis and a strongly positive cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) test. It is important to recognize this cause of positive c-ANCA because infectious endocarditis may closely mimic the clinical manifestations of ANCA-associated vasculitides such as Wegener granulomatosis or microscopic polyangiitis. Furthermore, ANCA-associated vasculitis may result in noninfectious endocarditis, which may be confused with bacterial endocarditis. In this paper, we review reported cases of ANCA-positive bacterial endocarditis and compare them to the reported cases of ANCA-associated idiopathic vasculitis with endocardial compromise.

Streptococcal viridans subacute bacterial endocarditis associated with antineutrophil cytoplasmic autoantibodies (ANCA).

We report an illustrative case of a 60-year-old man with Streptococcus viridans subacute bacterial endocarditis (SBE) and positive antineutrophil cytoplasmic autoantibodies (c-ANCA). C-ANCA positivity has been associated with a variety of rheumatic and infectious disease areas, but has been rarely associated with SBE. The patient had mitral valve prolapse with mitral regurgitation, and S viridans SBE developed after a dental procedure. Laboratory abnormalities included anemia, elevated erythrocyte sedimentation rate, positive rheumatoid factor, positive anticardiolipin antibody, positive lupus anticoagulant, and highly elevated c-ANCA level. We believe this is only the ninth reported case of S viridans SBE with a positive c-ANCA, and the third with mitral valve prolapse and vegetations.

Streptococcus sanguis secretes CD14-binding proteins that stimulate cytokine synthesis: a clue to the pathogenesis of infective (bacterial) endocarditis?

Streptococcus sanguis is the major causative organism of infective (bacterial) endocarditis but, surprisingly, almost nothing is known about how it induces endocardial inflammation. In earlier studies we have shown that many bacteria secrete potent cytokine-inducing or -inhibiting proteins. We have therefore isolated the material secreted by S. sanguis grown on blood agar or in broth culture and have tested its ability to induce human peripheral blood monocytes to synthesize pro-inflammatory cytokines. The activation of monocytes by the secreted components of S. sanguis was almost totally blocked by heat and trypsin treatment but not by the lipopolysaccharide-inactivating antibiotic, polymyxin B, suggesting that activity is due to secreted proteins. The activity of the secreted material was significantly reduced by anti-CD14 monoclonal antibodies suggesting that the active protein (or proteins) was binding to the CD14/Toll-like receptor (TLR)4 complex. Fractionation of the secreted proteins by high performance liquid chromatography (HPLC) identified two proteins as being responsible for the majority of the cytokine induction: a manganese-dependent superoxide dismutase and a 190 kDa protein, which could not be sequenced, but which was neither CshA nor the PI/II proteins. These proteins, or the receptors to which they bind, may be therapeutic targets and may allow the development of adjunctive therapies to prevent endocardial damage during the often prolonged treatment of infective endocarditis with antibiotics. In addition, blocking of CD14 may have some therapeutic benefit.

Subacute bacterial endocarditis with positive cytoplasmic antineutrophil cytoplasmic antibodies and anti-proteinase 3 antibodies.

OBJECTIVE: To report a potentially important limitation of antineutrophil cytoplasmic antibody (ANCA) testing: positive results in patients with subacute bacterial endocarditis (SBE). METHODS: We describe 3 patients with SBE who presented with features mimicking ANCA-associated vasculitis (AAV) and positive findings on tests for cytoplasmic ANCA (cANCA) by indirect immunofluorescence and for anti-proteinase 3 (anti-PR3)antibodies by antigen-specific enzyme-linked immunosorbent assay (ELISA). We also reviewed the published literature describing infectious diseases with (misinterpreted) positive ANCA results through a Medline search of English-language articles published between 1966 and January 1999. These previously reported cases were reinterpreted using an ANCA scoring system that combines the findings of immunofluorescence and antigen-specific ELISA testing. RESULTS: We are now aware of a total of 7 cases of SBE with positive cANCA and anti-PR3 antibodies. We are not aware of any cases of SBE associated with antimyeloperoxidase/perinuclear ANCA. Clinical manifestations mimicking AAV included glomerulonephritis, purpura, epistaxis, or sinus symptoms in 6 of the patients. Streptococcal species were identified in 5 patients, and cardiac valvular abnormalities were demonstrated in 6. All patients except 1, who died of a complication of SBE, recovered with antibiotic therapy. CONCLUSION: Findings of tests for anti-PR3/ cANCA antibodies may be positive in patients with SBE. When encountering ANCA positivity in patients suspected of having systemic vasculitis, physicians should take appropriate steps to rule out infectious diseases, including SBE, before committing the patient to long-term, aggressive immunosuppressive therapy.

The presence of cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA) in the course of subacute bacterial endocarditis with glomerular involvement, coincidence or association?

Antineutrophil cytoplasmic antibodies positivity with cytoplasmic pattern (C-ANCA) and proteinase-3 (PR-3) specificity was found in two patients with both subacute bacterial endocarditis (SBE) and glomerular involvement. Renal biopsy showed membranoproliferative glomerulonephritis in one case and focal segmental glomerulonephritis in the second case. Immunofluorescence study showed granular immune deposits in both cases evocating immune complex glomerulonephritis. Renal and biological manifestations disappeared with clinical improvement secondary to antibiotherapy. Physicians have to consider the possible occurrence of such C-PR-3 ANCA, claimed to be specific markers for Wegener's granulomatosis, in infectious diseases such as SBE. Hence we focus on the necessity of performing a renal biopsy with light microscopy and immunofluorescence studies in all patients with ANCA associated glomerular disease.

[Several mechanisms of immunological adaptation in the etiology of subacute infectious endocarditis]. / O nekotorykh mekhanizmakh immunologicheskoi adaptatsii pri razvitii podostrogo infektsionnogo éndokardita.

The paper deals with the possibility of identifying the persons predisposed to the development of subacute septic endocarditis (SSE), with the prediction of the course of the disease and the clarification of reasons for the inefficiency of antibacterial therapy. The studies performed revealed the impairment of cooperative interaction of the immune system, which prevents it from fulfilling its main task, i.e. to make an immunological surveillance over the maintenance of internal constancy. Imperfection of this function in SSE patients and rheumatic heart diseases is based on the body's sharply limited adaptation which results from the genetically determined low values of the immune functional reserve realizable by the level of intracellular energy processes which are substantially lower in SSE patients, as evidenced by the studies conducted. This is very important for predicting whether it may develop in some patients with rheumatic diseases. The necessity of using large doses of antibiotics decreases the activity of intracellular processes to a greater extent, aggravating primarily phagocytic function, as reflected in the efficiency of antibiotic therapy.

Circulating tumor necrosis factor alpha (TNF), soluble TNF receptors, and interleukin-6 in human subacute bacterial endocarditis.

Cell surface components of viridans streptococci and enterococci have been shown to stimulate the release of tumor necrosis factor alpha (TNF) and interleukin-6 from monocytes/macrophages. In the sera from 10 patients with subacute enterococcal or streptococcal endocarditis, however, the levels of both cytokines were low or undetectable, with elevated TNF levels on admission in 3 patients with complicated disease. Soluble TNF receptor levels were significantly elevated compared with those of healthy controls. When patients with malaria were used as a control group of acute intravascular infection with high circulating TNF values, the ratio between soluble TNF receptors and TNF on admission was significantly greater in the patients with subacute bacterial endocarditis. Besides different amounts of circulating TNF, enhanced TNF receptor shedding may have an important role in the pathogenesis of subacute versus acute clinical disease following human intravascular infection.

Serum antibody responses to Streptococcus mutans antigens in humans systemically infected with oral streptococci.

Sera from patients with subacute bacterial endocarditis (SBE) due to Streptococcus mutans or other oral streptococci and from normal subjects were assayed by enzyme-linked immunosorbent assay for antibodies to defined S. mutans antigens. Antibodies of IgG and IgA isotypes to Ag I/II and Ag III were greatly elevated in S. mutans-SBE sera, and the IgA antibodies in 3 sera included both polymeric and monomeric forms. Elevated IgM and IgG anti-lipoteichoic acid and IgG and IgA anti-serotype c polysaccharide antibodies were also found. The sera of 4 of 6 patients infected with other oral streptococci also displayed antibodies to S. mutans Ag I/II. Sera of 3 patients infected with Streptococcus mitis or Streptococcus oralis, but none of the S. mutans-infected cases, showed elevated antibodies to human heart sarcolemma, and all SBE sera had elevated rheumatoid factor. These results suggest that the known surface protein antigens of S. mutans are immunodominant in humans, and are not likely to be heart cross-reactive.

Antibodies reactive with streptococcal peptidoglycan-polysaccharide complexes in rheumatic fever, subacute bacterial endocarditis and tuberculosis.

Serum antibodies reactive with streptococcal peptidoglycan-polysaccharide complexes (PG-PS) have been estimated by enzyme-linked immunosorbent assay in patients with acute rheumatic fever (ARF), tuberculosis (TB) and subacute bacterial endocarditis (SBE) compared with normal age- and sex-matched controls. IgG2 and IgG3 were the predominant subclasses of antibodies in TB and SBE, whereas in ARF IgG1, IgG2 and IgG3 antibodies were detected. IgG4 antibodies were detected only infrequently. Antibodies of the IgG subclasses were detected in a greater proportion of sera when the PG-PS antigen was further purified by extraction with sodium dodecyl sulphate.

Evaluation of anti-C1q capture assay for detecting circulating immune complexes and comparison with polyethylene glycol-immunoglobulin G, C1q-binding, and Raji cell methods.

An anti-C1q capture method kit (C1q-immunoglobulin G [IgG]) (Ortho Diagnostics, Inc., Raritan, N.J.) for measuring circulating immune complexes (CIC) was evaluated. The kit showed poor diagnostic sensitivity (P less than 0.005) for identifying CIC in patients with systemic lupus, rheumatoid arthritis, and bacterial endocarditis, as compared with polyethylene glycol-IgG and Raji cell tests (12, 24, and 24 positive, respectively, of 31 patients). Of the patients who were positive with the C1q-IgG test, 25% showed discrepancies when their results were compared with the polyethylene glycol-IgG and C1q-binding test results. Gel filtration chromatography of two of these discrepant sera showed the only peak of C1q-IgG activity to be associated with monomeric IgG (molecular weight, less than 200,000). We concluded that the kit method may be measuring substances other than CIC in some sera, because molecules of C1q attached to IgG should exhibit a molecular weight of greater than 500,000.

Splenic immune deposits in bacterial endocarditis.

Splenic and renal tissues from a 61-year-old man with subacute bacterial endocarditis and acute renal failure were studied. Immune complex deposits were found both within glomeruli and splenic venous sinus basement membranes, substantiating the systemic nature of the immune injury in this disorder. The splenic deposits may, in part, be responsible for the splenomegaly often present in endocarditis.

Appearance of low molecular weight IgM during course of infective endocarditis.

Low molecular weight (LMW) IgM is the monomeric subunit of pentameric IgM. It is not found in healthy adults but occurs in a number of autoimmune, lymphoproliferative and infectious conditions. It has not been described before in infective endocarditis (IE). Eighteen patients with IE were studied; 16 with subacute bacterial endocarditis (SBE) and two with acute endocarditis. LMW IgM was detected in the sera of six patients, all having SBE in association with circulating rheumatoid factor (RF). Of the remaining 12 patients without LMW IgM only three had RF in low quantities. Sequential studies revealed that LMW IgM appeared during the later stages of the illness at or following the peak RF and IgM response. LMW IgM was not detected in any of 20 control sera. Immunoblot analysis of sera containing LMW IgM revealed the presence of small quantities of dimeric and oligomeric IgM in addition to monomeric IgM. We conclude that LMW IgM occurs predominantly in those patients with IE who have associated RF. Immunoblot analysis suggests that the presence of monomeric and oligomeric LMW IgM reflects a disorder of IgM polymerization occurring in those patients.