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.

Serum opsonin, bacteria, and polymorphonuclear leukocyte interactions in subacute bacterial endocarditis. Anti-gamma-globulin factors and their interaction with specific opsonins.

The effect of anti-gamma-globulin factors on 7S gamma-globulin opsonins from patients with subacute bacterial endocarditis has been examined with a quantitative in vitro phagocytosis system. Human anti-gamma-globulin factors from patients with subacute bacterial endocarditis and rheumatoid arthritis inhibited the opsonic action of 7S gamma-globulin specifically bound to bacteria. A similar antiopsonic effect was obtained with rabbit antiserum to human gammaG globulin. The antiopsonic effect of anti-gamma-globulin factors did not correlate with their ability to potentiate agglutination of bacteria by 7S antibody. Competition was demonstrated between the antiopsonic effect of anti-gamma-globulin factors and the phagocytosis-promoting action of heat-labile serum factors containing hemolytically active complement.

Studies of human sera with cytotoxic activity.

42 human sera showing in vitro cytotoxic activity of restricted or broad HL-A specificities with test human lymphocytes were studied for the molecular and immunoglobulin class of cytotoxic antibody using sucrose gradient separations, DEAE-cellulose chromatography, and Sephadex G-200 gel filtration. Sera originated from patients with previous multiple pregnancies (19), multiply transfused patients (8), subacute bacterial endocarditis (4), systemic lupus (2), and human umbilical cord sera (9). In 32 of 42 instances, predominant cytotoxic activity was found in high molecular weight gradient fractions; however, DEAE chromatographic separations revealed cytotoxic activity in initial buffer fractions containing primarily gammaG globulin. Gradient separations of cytotoxic activity within initial gammaG DEAE fractions showed localization of cytotoxicity only in high molecular weight materials. Confirmation of high molecular weight gammaG cytotoxic activity was obtained by resistance to mercaptoethanol treatment, abolition of activity after absorption only with specific anti-gammaG antisera, and by the finding that high molecular weight cytotoxic activity in gradients or gel filtration run at neutral pH 7.4 became 7S when separations were rerun at an acidic pH of 4.0. Such 7S activity again became rapidly sedimenting when the same fractions were again rerun in gradients at neutral pH.19S gammaM cytotoxic activity was documented in a panel of 15 human sera containing anti-"I" cold agglutinins. In this instance the cytotoxic activity appeared to be related to the cold agglutinin antibody since it was mercaptoethanol sensitive and could be demonstrated in monoclonal antibody eluates containing primarily gammaM. No in vitro protection again cytotoxic effect was demonstrated when isolated human 19S anti-gamma-globulins were aded to the lymphocytotoxic assay system. With the exception of cold agglutinins, human cytotoxic antibodies appear to be primarily gammaG producing in vitro lymphocyte killing either as 7S gammaG globulin or as rapidly sedimenting aggregates or complexes of gammaG molecules.

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.

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.

Vascular disease in infective endocarditis. Report of immune-mediated events in skin and brain.

A patient with subacute bacterial endocarditis, who had a prosthetic mitral valve, exhibited hypocomplementemia, mixed (IgG, IgM) cryoglobulinemia, and widespread dermal vasculitis with IgM deposited at the dermoepidermal junction. Postmortem findings included immune-complex glomerulonephritis and deposits of IgG in the choroid plexus. These findings are consistent with a generalized vasculitis, which may be mediated by circulating immune complexes; basement membrane localization of immune complexes to the skin and choroid plexus appears not to be specific for systemic lupus erythematosus, as has been previously thought, but may represent the general phenomenon of immune-mediated pathogenesis.

A solid-phase assay for circulating immune complexes using monoclonal rheumatoid factors and peroxidase-linked protein A.

A solid-phase monoclonal rheumatoid factor (mRF) assay for circulating immune complexes (IC) is described. Microtiter plates are coated with mRF, serum diluted 1 : 40 is added, and complexed IgG is detected with protein A coupled to peroxidase. Selective binding was obtained with aggregated human gamma-globulin and soluble IC prepared in vitro. Sucrose density gradient ultracentrifugation studies indicate that mRF binds intermediate-size IC (between 7S and 19S). Abnormal levels of IC were found in 78% of sera from patients with rheumatoid arthritis, 67% with systemic lupus erythematosus, and 87% with subacute bacterial endocarditis.

Fate of circulating immune complexes in infective endocarditis.

To examine the role of circulating immune complexes (CIC) in infective endocarditis, we studied 64 patients with infective endocarditis for the presence of CIC by the polyethylene-glycol (PEG)-precipitation test and the Clq binding test. This study was repeated during the course of the disease in 23 patients. CIC were found in 84 per cent of patients (66 per cent with acute infective endocarditis, 89 per cent with subacute infective endocarditis) during the active phase of the disease. Higer PEG precipitates were associated with typical cutaneous signs, cryoglobulins and nonstreptococcic culture-positive infective endocarditis. Under appropriate antibiotic treatment, the PEG precipitate levels of 17 patients fell within 1 month to the normal range, with a concomitant drop in cryoglobulinemia and rheumatoid factor. Conversely, uncontrolled sepsis always (six of six) yielded a rising level of CIC. These findings support the hypothesis that CIC may be important in the pathogenesis of peripheral lesions in infective endocarditis.

Symposium on the immunodiagnosis of rheumatic and related diseases, Part II. Rheumatoid factors.

Human rheumatoid factors are antibodies of IgG, IgA, or IgM class that show reactions with antigenic determinants present on other immunoglobulin molecules. The most commonly measured rheumatoid factor relates to the 19S IgM type, which reacts by agglutination of latex particles coated with 7S IgG and is often measured in the standard latex fixation test. Approximately 65 to 70 per cent of patients with rheumatoid arthritis show positive serologic tests for rheumatoid factor; however, a number of other chronic disease conditions are also associated with positive rheumatoid factor reactions, including infective endocarditis, sarcoidosis, leprosy, and other hyperglobulinemic conditions. Although extensive serologic and immunochemical studies have identified a number of specific antigenic structural sites on immunoglobulin molecules that react with rheumatoid factors, recent studies have shown that a certain proportion of such antibodies may show cross-reactivity with DNA-histone complexes as well. It is still not entirely clear how rheumatoid factors fit into the pathogenesis of rheumatoid arthritis itself.

Circulating immune complexes in subacute infective endocarditis and post-streptococcal glomerulonephritis.

Two out of five patients with subacute infective endocarditis and two patients with post-streptococcal glomerulonephritis had large amounts of soluble circulating immune complexes in their sera. The three others with endocarditis had less severe disease and minimal evidence of circulating immune complexes. Low serum complement was also found in two of the cases.

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.

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.

[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.

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.

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.