Hidehiro Tsuneoka

Bartonella Infection Associated with Systemic Juvenile Rheumatoid Arthritis

A 4-year-old girl with systemic juvenile rheumatoid arthritis had Bartonella infection diagnosed serologically. This case suggested that Bartonella (most probably Bartonella henselae) infection may in part be responsible for the development of systemic juvenile rheumatoid arthritis.

Anti-phospholipid antibodies contribute to arteriosclerosis in patients with systemic lupus erythematosus through induction of tissue factor expression and cytokine production from peripheral blood mononuclear cells

INTRODUCTION In systemic lupus erythematosus (SLE) patients, the prevalence of arteriosclerosis obliterans (ASO) is high despite a lack of common risk factors for ASO. The main objective of this study was to investigate a possible direct role of anti-phospholipid antibodies (aPLs), which are frequently detected in SLE patients, in the pathogenesis of ASO. MATERIALS AND METHODS We examined tissue factor (TF) expression on the monocyte surface by flow cytometric analysis in 89 SLE patients with or without ASO and/or aPLs and studied the in vitro effect of purified IgG fractions from plasma of SLE patients or normal healthy volunteers (aPLs(+) IgG, n=8; aPLs(-) IgG, n=6; Normal IgG, n=6) on the expression of TF and production of TNF-α and IL-1β in healthy peripheral blood mononuclear cells (PBMCs) or isolated monocytes. RESULTS We confirmed that high expression of monocyte TF was strongly associated with the prevalence of ASO and the presence of aPLs. Treatments of PBMCs with aPLs(-) IgG or normal IgG did not significantly increase expression of TF, TNF-α, and IL-1β messenger RNA (mRNA) and the production of TNF-α and IL-1β. However, stimulation of PBMCs with aPLs(+) IgG caused significant increase in expression of TF, TNF-α, and IL-1β mRNA. Moreover, aPLs(+) IgG stimulated PBMCs and significantly enhanced the production of TNF-α and IL-1β. CONCLUSION These results suggest that IgG-aPLs cause persistently high TF expression and inflammatory cytokine production by interacting with peripheral blood monocytes and lymphocytes, which may be an important mechanism in the pathogenesis of ASO peculiar to SLE patients.

Evaluation of Indirect Fluorescence Antibody Assay for Detection of Bartonella clarridgeiae and Seroprevalence of B. clarridgeiae among Patients with Suspected Cat Scratch Disease

ABSTRACT The possibility of Bartonella clarridgeiae being a causative agent of cat scratch disease (CSD) was investigated by using indirect fluorescence antibody assays with 288 suspected CSD patients. Immunoglobulin G antibody to noncocultivated B. clarridgeiae was suitable only for detection of B. clarridgeiae antibody. Significant cross-reactivity between Bartonella henselae and B. clarridgeiae was noted, and no CSD case caused by B. clarridgeiae was detected.

Acquired activated protein C resistance is associated with IgG antibodies to protein S in patients with systemic lupus erythematosus

The objective of this study was to clarify the roles of anti-phospholipid antibodies (aPLs) in the pathogenesis of acquired activated protein C resistance (APC-R) in patients with systemic lupus erythematosus (SLE). We examined several aPLs levels (lupus anticoagulant, anti-cardiolipin antibodies, anti-beta2-glycoprotein I antibodies, anti-protein C antibodies, and anti-protein S antibodies), the APC-R test, and the factor V Leiden test in 85 SLE patients. Acquired APC-R, which was not found in any patient with the factor V Leiden mutation, was present in 26 (30.6%) of 85 patients, and confirmed that acquired APC-R was a significant risk factor for thromboembolic complications [odd ratio (OR), 3.36; 95% confidence interval (CI), 1.24-9.11]. Multivariate logistic analysis revealed that both LA and anti-PS strongly associated with the presence of APC-R, and that the correlation between anti-PS and APC-R was much stronger (OR, 46.7; 95%CI, 6.99-311) than that between LA and APC-R (OR, 11.3; 95%CI, 2.26-57.0). Furthermore, the mean value of APC sensitivity ratios was significantly lower in SLE patients with anti-PS (mean +/- SD, 1.68 +/- 0.37, p < 0.0001) than in those without anti-PS (2.23 +/- 0.40). These results suggest that acquired APC-R is most strongly attributable to functional interference of the APC pathway by anti-PS, which contribute to risk of thromboembolic complications.

A novel ELISA system for simultaneous detection of six subclasses of anti-phospholipid antibodies for prediction of thrombotic complications among SLE patients

BACKGROUND Anti-phospholipid antibodies (aPLs) are frequently associated with arterial and/or venous thromboembolic complications and recurrent fetal loss in patients with systemic lupus erythematosus (SLE). We recently reported that the clinical picture of SLE apparently depends on subclasses of aPLs in the patients sera, but the contribution of each subclass remains uncertain. METHODS We newly developed an ELISA system for simultaneous detection of six specific categories of aPLs: anti-cardiolipin (aCL), anti-β2-glycoprotein I (aβ2GPI), anti-cardiolipin/β2-glycoprotein I (aCL/β2GPI), anti-phosphatidylserine (aPS), anti-prothrombin (aPT), and anti-phosphatidylserine/prothrombin (aPS/PT). They were measured in 331 patients with SLE including 63 patients with arterial thromboembolic complications, 64 with venous thromboembolic complications, and 43 with recurrent fetal loss. Lupus anticoagulant (LA) activity in their plasma was measured according to the guidelines recommended by the Subcommittee on Lupus Anticoagulant/Phospholipid-Dependent Antibodies. RESULTS Multivariate logistic analysis revealed that the concentration of aPS/PT was most closely associated with arterial thrombosis. In contrast, the concentration of aβ2GPI was most closely related to venous thrombosis. Furthermore, both aCL/β2GPI and aPS/PT were independently associated with episodes of recurrent fetal loss. Regarding the relation between APLs and LA activity, aPS/PT, followed by aβ2GPI and aPT, showed the closest association with the presence of LA activity. CONCLUSIONS Anti-phospholipid syndrome in patients with SLE can be classified by antigenic specificities of their aPLs as to their susceptibility to arterial and/or venous thromboembolic complications or obstetric complications.

Prosthetic valve endocarditis caused by Bartonella quintana in a patient during immunosuppressive therapies for collagen vascular diseases

Bartonella quintana, known to cause various clinical symptoms, is increasingly recognized as one important cause of culture-negative endocarditis. We report a case of infectious endocarditis with B. quintana on the prosthetic valve, accompanied by proteinase 3-antineutrophil cytoplasmic antibody-positive collagen vascular disease-like symptoms 1 year earlier.

‘Oxidation stress index’ as a possible clinical marker for the evaluation of non-Hodgkin lymphoma

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A first Japanese case of Bartonella henselae-induced endocarditis diagnosed by prolonged culture of a specimen from the excised valve.

Bartonella henselae, the causative agent of cat scratch disease, is increasingly recognized as a cause of culture-negative endocarditis. This report describes the first Japanese case, which was diagnosed after a prolonged culture of the excised aortic valve. High IgG and IgM titers to B. henselae pointed to a subacute course of the disease.

Molecular typing of Bartonella henselae DNA extracted from human clinical specimens and cat isolates in Japan.

Bartonella henselae is the causative agent of cat scratch disease (CSD). To clarify the population structure and relationship between human and cat strains of B. henselae, 55 specimens isolated in Japan, including 24 B. henselae DNA-positive clinical samples from CSD patients and 31 B. henselae isolates from domestic cats, were characterized by multilocus sequence typing (MLST) and the 16S-23S tRNA-Ala/tRNA-Ile intergenic spacer (S1) sequence, which were used previously for strain typing of B. henselae. Three different sequence types (STs) were identified by MLST, one of which was novel. Fifty-two strains (94.5%), including all strains detected in CSD patients, were assigned to ST-1. Eight S1 genotypes were observed, three of which were novel. The 52 ST-1 strains were classified into seven S1 genotypes, two of which were predominant in both human and cat strains. In addition, 5.5% of the strains (3/55) contained two different intergenic spacer S1 copies. These results indicate that the predominant B. henselae MLST ST-1 in Japan is a significantly genetically diverse population on the basis of the sequence diversity of intergenic spacer S1, and that highly prevalent S1 genotypes among cats are often involved in human infections.

Multispacer Typing of Bartonella henselae Isolates from Humans and Cats, Japan

To determine genotypic distribution of and relationship between human and cat strains of Bartonella henselae, we characterized 56 specimens using multispacer typing (MST). Of 13 MST genotypes identified, 12 were grouped into cluster 1. In Japan, human infections can be caused by B. henselae strains in cluster 1.