IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus.

OBJECTIVE: To determine whether the intrathecal concentrations of cytokines/chemokines are associated with, or influenced by, serum concentrations in patients with central neuropsychiatric systemic lupus erythematosus (NPSLE), and to ascertain whether the increased production of cytokines/chemokines intrathecally relative to serum levels is associated with the presence of central NPSLE. METHODS: 52 SLE patients (30 with central NPSLE and 22 with non-NPSLE), for whom the CSF and serum samples were obtained at the same time, were enrolled. 27 kinds of cytokine/chemokine concentrations other than IFN-α in the cerebrospinal fluid (CSF) and serum samples were measured by Bio-Plex Pro Assays. IFN-α concentration and anti-ribosomal P protein antibody (anti-P) titres in CSF and serum samples were measured by ELISA. RESULTS: The mean concentrations of IL-6, IL-8, IP-10, MCP-1, G-CSF and GM-CSF were higher in the CSF than in the sera, respectively, while the mean concentrations of other 22 cytokines/chemokines, including RANTES and IFN-α, in the CSF were much lower than those in the sera, respectively. Furthermore, the concentrations of IL-6, IL-8, IP-10, MCP-1 and G-CSF in the CSF of the 30 patients with NPSLE were significantly higher than in the 22 patients with non-NPSLE (p = 6.82 × 10(-5), p = 0.00037, p = 0.0028, p = 0.00065, and p = 0.0001, respectively), while the concentration of GM-CSF in the CSF of the 30 patients with NPSLE was not significantly higher than in the 22 patients with non-NPSLE. Most importantly, the largest difference occurred in CSF IL-6 concentrations. A significant positive correlation between CSF anti-P titres and serum anti-P titres in 52 patients with SLE (r = 0.6316, p = 6.44 × 10(-6)) was found, while no significant positive correlation was observed between CSF levels and serum levels of each cytokine/chemokine in the 52 SLE patients. CONCLUSION: In central NPSLE the production of IL-6, IL-8, IP-10, MCP-1 and G-CSF might take place in the central nervous system (CNS). These increased CSF cytokines/chemokines along with anti-P might have a prerequisite role in the pathogenesis of central NPSLE.

Migraine in patients with systemic lupus erythematosus is associated with reduced cerebral grey matter volume but not with measures of glial activation or anti-NR2 or anti-P antibodies.

BACKGROUND AND PURPOSE: Migraine is frequent in patients with systemic lupus erythematosus (SLE), but the pathogenesis and pathophysiology are poorly understood. Migraine is assumed to be a consequence of abnormal neuronal excitability. Based on the hypothesis that the threshold for migraine is lower in SLE patients due to cerebral disturbances, whether structural abnormalities of the brain or relevant biomarkers are associated with headaches in SLE was investigated. METHODS: Sixty-seven SLE patients and age- and gender-matched healthy subjects participated. Volumes of grey matter (GM) and white matter (WM) were estimated from cerebral magnetic resonance images with SPM8 software. Anti-NR2 and anti-P antibodies and protein S100B were measured in cerebrospinal fluid. RESULTS: In regression analyses, larger GM volumes in SLE patients reduced the odds for headache in general [odds ratio (OR) 0.98, P = 0.048] and for migraine in particular (OR 0.95, P = 0.004). No localized loss of GM was observed. Larger WM volumes in patients increased the odds for migraine (OR 1.04, P = 0.007). These findings could not be confirmed in healthy subjects. Neither anti-NR2 and anti-P antibodies nor S100B were associated with headaches in SLE patients. CONCLUSIONS: Systemic lupus erythematosus patients with migraine have a diffuse reduction in GM compared to patients without migraine. This finding was not observed in healthy subjects with migraine, and selected biomarkers did not indicate specific pathophysiological processes in the brain. These findings indicate that unknown pathogenic processes are responsible for the increased frequency of migraine in SLE patients.

Association of a single nucleotide polymorphism in the SH2D1A intronic region with systemic lupus erythematosus.

SH2D1A, also known as signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), is an adaptor protein. Recently, it was reported that SAP deficient mice were protected from systemic lupus erythematosus (SLE). In this study, we postulated SH2D1A gene to be a candidate susceptibility gene for SLE and analyzed its association with SLE. A case-control association study was conducted on 5 tag single nucleotide polymorphisms (SNPs) in SH2D1A region in 506 Japanese female SLE patients and 330 healthy female controls. The luciferase assay was performed to determine the functional role of the SNP associated with SLE. One SNP in the intron 2, rs2049995, showed association with SLE (p=0.0110, odds ratio (OR) 1.97, 95% confidence interval (CI) 1.16-3.34, under the dominant model). The association of rs2049995 seemed to be stronger in the subset with the age of onset less than 20 years (p=0.0067, OR 2.65, 95% CI 1.28-5.46). Functional evaluation of rs2049995 showed that reporter gene activity was increased 1.9-fold for the susceptible allele compared with the resistant allele. An intronic SNP of SH2D1A is associated with SLE.

Efficacy of serum angiopoietin-1 measurement in the diagnosis of early rheumatoid arthritis.

OBJECTIVES: Previous studies showed that angiopoietin-1(Ang-1) expression was increased in the synovium in early rheumatoid arthritis (RA) patients. The present study was therefore designed to examine whether determination of serum Ang-1 might be effective in diagnosis of early RA. METHODS: One hundred and five serum samples of RA (21 males, 84 females) were studied for serum Ang-1 level. Serum samples were also collected from other collagen diseases, including 35 cases of SLE, 29 cases of systemic sclerosis, 16 cases of polymyositis/dermatomyositis. Serum samples were additionally obtained from 34 patients who visited our clinic for evaluation of symmetrical polyarthritis with morning stiffness. After one year of follow-up, those patients who satisfied the ACR 1987 classification criteria for RA were defined as 'early RA'. Serum Ang-1 levels were measured by sandwich ELISA using anti-angiopoietin-1 antibodies (both monoclonal and polyclonal antibodies). Serum anti-CCP antibody and rheumatoid factor (RF) were measured by ELISA and by laser nepherometry, respectively. RESULTS: Serum Ang-1 in RA patients was significantly higher than those in other collagen diseases. Serum Ang-1 levels in 50 normal healthy individuals were 5.8 ± 0.31 pg/ml (mean ± SEM). There was no significant difference in CRP and serum RF at the first visit between early RA patients and non-RA patients, whereas serum Ang-1 levels at the first visit were significantly higher in early RA (58.7 ± 17.9 pg/ml [mean ± SEM]) than those in non-RA (8.2 ± 4.5 pg/ml). ROC analysis revealed that serum Ang-1 (cut-off 23.91 pg/ml) could diagnose early RA at sensitivity 57.1% and specificity 84.6%, providing comparable area under the curve (0.71, 95% CI: 0.54-0.88) to that of serum anti-CCP antibody (0.72, 95% CI: 0.53-0.92). There was no significant correlation between anti-CCP antibody and Ang-1. CONCLUSIONS: These results indicate that serum Ang-1 is as useful a marker for the diagnosis of early RA as serum anti-CCP antibody.

Regulation of mechanical stress-induced MMP-13 and ADAMTS-5 expression by RUNX-2 transcriptional factor in SW1353 chondrocyte-like cells.

OBJECTIVE: To investigate the mechanism of mechanical stress-induced expression and regulation of aggrecanases and examine the role of runt-related transcription factor 2 (RUNX-2) in chondrocyte-like cells. METHODS: SW1353 cells were seeded onto stretch chambers at a concentration of 5×104 cells/chamber, and a uni-axial cyclic tensile strain (CTS) (0.5 Hz, 10% stretch) was applied for 30 min. Total RNA was extracted, reverse transcribed, and analyzed by polymerase chain reaction (PCR) and real-time PCR. RUNX-2 overexpression and small interfering RNA (siRNA) targeting RUNX-2 were used to investigate the role of RUNX-2 in CTS-induced gene expression. The involvement of diverse mitogen-activated protein kinase (MAPK) pathways in the activation of RUNX-2, MMP-13 and ADAMTS-5 during CTS was examined by Western blotting. RESULTS: CTS induced expression of RUNX-2, MMP-13, ADAMTS-4, -5, and -9. Overexpression of RUNX-2 up-regulated expression of MMP-13 and ADAMTS-5, whereas RUNX-2 siRNA resulted in significant down-regulation of mechanically-induced MMP-13 and ADAMTS-5 expression. CTS induced activation of p38 MAPK, and CTS induction of RUNX-2, MMP-13 and ADAMTS-5 mRNA was down-regulated by the selective p38 MAPK inhibitor SB203580 but not by the p44/42 MAPK inhibitor U0126, or the JNK MAPK inhibitor JNK inhibitor II. CONCLUSIONS: RUNX-2 might have a role as a key downstream mediator of p38's ability to regulate mechanical stress-induced MMP-13 and ADAMTS-5 expression.

Enhanced expression of mRNA for FK506-binding protein 5 in bone marrow CD34 positive cells in patients with rheumatoid arthritis.

OBJECTIVE: Recent studies have disclosed that several genes are up-regulated in bone marrow (BM) mononuclear cells from rheumatoid arthritis (RA) patients. However, it remains unclear whether such abnormalities result from systemic inflammation or from abnormalities at stem cell level. The current study therefore examined the expression of several representative genes, including amphiregulin (AREG), chemokine receptor 4 (CXCR4), and FK506-binding protein 5 (FKBP5) in RA BM CD34+ cells. METHODS: BM samples were obtained from 52 patients with RA and 35 patients with osteroarthritis (OA) during joint operations. CD34+ cells were purified from the BM mononuclear cells by positive selection with magnetic beads. The mRNA expression for AREG, CXCR4, and FKBP5 was measured using quantitative real-time PCR. RESULTS: The expression of mRNA for FKBP5, but not that of AREG or CXCR4, was significantly higher in RA BM CD34+ cells than in OA BM CD34+ cells. The FKBP5 mRNA expression level was not correlated with serum CRP or treatment. In addition, tumour necrosis factor-alpha did not enhance the expression of FKBP5 mRNA in BM CD34+ cells from healthy donors. CONCLUSION: The results suggest that the enhanced expression of FKBP5 in BM CD34+ cells might be an intrinsic abnormality of RA BM CD34+ cells, whereas the enhanced expression of AREG and CXCR4 in BM mononuclear cells might be secondary to systemic inflammation.

Identification of autoantigens specific for systemic lupus erythematosus with central nervous system involvement.

Using proteomic analysis, we identified candidate autoantigens specific for central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). Proteins, extracted from cultured human neuroblastoma cells, were separated both by SDS-PAGE (1-DE) and two-dimensional electrophoresis (2-DE), and transferred to membranes. Western blot analysis was performed using serum samples from 30 SLE patients with CNS involvement (CNS-Lupus) and from 30 SLE patients without CNS involvement (non-CNS-SLE). The detected autoantigens were identified using MALDI-TOF/TOF MS. On the 1-DE Western blot, we detected 32 antigenic bands in the serum samples from the CNS-Lupus patients. Among them, four bands were detected significantly more frequently in the CNS-Lupus patients than in the non-CNS-SLE patients. Three bands were detected in four or more of the CNS-Lupus patients but in only one or none of the non-CNS-SLE patients. We thus selected these seven bands for the next investigations. Next, we detected protein spots corresponding to the selected seven bands by 2-DE Western blot and identified four proteins. They are peroxiredoxin-4, ubiquitin carboxyl-terminal hydrolase isozyme L1, splicing factor arginine/serine-rich 3, and histone H2A type 1. These four candidate autoantigens for the anti-neuronal cell antibodies would be a useful marker for CNS-Lupus.

Regulation of cellular immunity prevents Helicobacter pylori-induced atherosclerosis.

Helicobacter pylori (H. pylori) is a predominant pathogen that causes not only gastroduodenal diseases but also extra-alimentary tract diseases. In this study, we demonstrated that H. pylori infection promoted atherogenesis in heterozygous apoe(+/ --) ldlr(+/--) mice. The male mice were fed with high fat diet from the age of 6 weeks. At the age of 16 weeks, development of atherosclerotic lesions was observed in the H. pylori-infected mice, and it seemed to be associated with an elevation of Th1-immune response against H. pylori origin-heat shock protein 60 (Hp-HSP60) and an increment of transendothelial migration of T cells. Subcutaneous immunisation with Hp-HSP60 or H. pylori eradication with antibiotics significantly reduced the progression of atherosclerosis, accompanied by a decline of Th1 differentiation and reduction of their chemotaxis beyond the endothelium. Thus, oral infection with H. pylori accelerates atherosclerosis in mice and the active immunisation with Hp-HSP60 or the eradication of H. pylori with antibiotics can moderate/prevent cellular immunity, resulting in a reduction of atherosclerosis.

Histopathology of the ruptured pulmonary artery aneurysm in a patient with Behçet's disease.

OBJECTIVE: Vascular involvement (vasculo-Behçet's disease) is relatively common in Behçet's disease. Although pulmonary artery aneurysm (PAA) is rare, it is the most serious and sometimes fatal complication. However, the mechanism of the development of PAA is unclear. In the present study, we carried out immunohistological examination of the ruptured pulmonary aneurysm in a patient with vasculo-Behçets disease. METHODS: Light microscopic examination was carried out on paraffin-embedded sections of autopsied pulmonary arteries of a Behçet's disease patient who died of the rupture of the left pulmonary artery aneurysm. RESULTS: Histopathology of the ruptured aneurysm revealed the formation of thrombus and recanalization. In addition, there was proliferation of small vessels in the vascular wall, as if the recanalization was extended to the vascular wall. Of note, marked perivascular cuffing of mononuclear cells, consisting of CD45RO+ T cells and CD68+ monocytes, were observed around the recanalizing capillaries as well as around the proliferating small vessels in the wall of the pulmonary artery. Of note, pericapillary infiltration of CD20+ B cells was noted exclusively in the vascular wall. The ruptured portion of the aneurysm lacks the lamina elastica, indicating that the aneurysm was so called pseudo-aneurysm. CONCLUSION: It is likely that the first event might be the formation of inflammatory thrombus in the pulmonary artery. During the process of recanalization of the thrombus, the basic inflammatory process of Behçet's disease caused marked angiogenesis as well as perivascular cuffing of inflammatory cells in the thrombus and the wall, leading to fragility of the wall.

A prospective comparison of nursing home-acquired pneumonia with hospital-acquired pneumonia in non-intubated elderly.

There are no prospective comparison of the etiology and clinical outcome between hospital-acquired pneumonia (HAP) and nursing home-acquired pneumonia (NHAP) in non-intubated elderly. This study prospectively evaluated the etiology of HAP and NHAP in non-intubated elderly. A prospective cohort study was carried out in a rural region of Japan where the population over 65 years of age represents 30% of the population. A total of 108 patients were enrolled. There were 33 patients with HAP and 75 with NHAP. Etiologic diagnosis was established in 78.8% of HAP and in 72% of NHAP patients. The most frequent pathogens were Chlamydophila pneumoniae followed by Streptococcus pneumoniae, Staphylococcus aureus and Influenza virus. The frequency of Streptococcus pneumoniae and Influenza virus was significantly higher, whereas the frequency of Staphylococcus aureus and Enterobacteriaceae was significantly lower in NHAP compared to HAP. Performance and nutritional status were significantly worse in patients with HAP than in those with NHAP. Hospital mortality was significantly lower in patients with NHAP compared to those with HAP. This study demonstrated that C. pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus and Influenza virus are frequent causative agents of pneumonia in non-intubated elderly and that the responsible pathogens and clinical outcome differ between NHAP and HAP.

Clinical characteristics of cytomegalovirus infection in rheumatic diseases: multicentre survey in a large patient population.

OBJECTIVE: To survey and elucidate the clinical characteristics of CMV infection in rheumatic disease patients. METHODS: A detailed questionnaire survey on CMV infection was carried out against rheumatic disease patients hospitalized in member hospitals, and the obtained clinical and/or laboratory data were analysed. RESULTS: Out of 7377 patients, 151 were diagnosed as having CMV infection. The underlying diseases ranged broadly, but SLE, microscopic polyangiitis, and dermatomyositis were the most common. Four were diagnosed histopathologically, and the others via positive CMV antigenaemia. In addition to oral corticosteroid for all but one patient, 81 were treated with pulsed methylprednisolone (MPSL), 64 with cyclophosphamide (CYC) and 36 with other immunosuppressants. Forty-four had a fatal outcome, for which presence of clinical symptoms, other infectious complications, lymphopenia, an older age (>59.3 yrs) and the use of pulsed MPSL were significant risk factors (P < 0.05) by univariate analysis. Multivariate analysis retained the first three (P < 0.05). The CMV antigenaemia count was significantly higher for the symptomatic than asymptomatic [10.1 (0.0-2998.0) vs 4.0 (1.3-1144.4)/10(5) PMNs, respectively, P < 0.05; threshold count: 5.6/10(5) PMNs]. No treatment benefit by anti-viral agent was observed as for survival. CONCLUSION: CMV infection was mostly diagnosed by antigenaemia, and occurred among patients under strong immunosuppressive therapy using pulsed MPSL and/or immunosuppressants. Lymphopenia, presence of symptoms and other infections are significant risk factors for a poor outcome and pulsed MPSL and an older age may predict it. Patients were prone to be symptomatic with anti-genaemia count over 5.6/10(5) PMNs.

Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced arthritis mouse model.

OBJECTIVE: To investigate the effect of the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), on joint inflammation and cartilage degeneration in a collagen antibody-induced arthritis (CAIA) mouse model. METHODS: CAIA mice were given daily subcutaneous injections of various concentrations of TSA (0, 0.5, 1.0, and 2.0 mg/kg) and various parameters were monitored for 14 days. On Day 15, the hind paws were examined histologically. To investigate the effects of TSA on the expressions of matrix metalloproteinase (MMP)-3, MMP-13, tissue inhibitor of MMP-1 (TIMP-1), and acetyl-H4 by chondrocytes, another group of mice was sacrificed on Day 6. In vitro direct effect of TSA was examined by real-time PCR for mRNA of type II collagen, aggrecan, MMP-3, and MMP-13 in murine chondrogenic ATDC5 cells after pro-inflammatory cytokine stimulation. RESULTS: In the TSA-treated group, clinical arthritis was significantly ameliorated in a dose-dependent manner. The severity of synovial inflammation and the cartilage destruction score were significantly lower in the TSA 2.0 mg/kg group compared to the other TSA-treated groups. On immunohistochemistry, the number of MMP-3 and MMP-13-positive chondrocytes was significantly lower in the TSA 2.0 mg/kg group than in the control group. In contrast, the number of TIMP-1-positive cells and acetyl-histone H4-positive cells was significantly higher in the TSA 2.0mg/kg group than in the control group. TSA suppressed interleukin 1-beta and tumor necrosis factor-alpha-stimulated up-regulation of MMP-3, but not MMP-13 mRNA expression by ATDC5. CONCLUSION: The systemic administration of TSA ameliorated synovial inflammation in CAIA mice. Subsequently cartilage destruction was also suppressed by TSA, at least in part, by modulating chondrocyte gene expression.

Myocardial infarction caused by rheumatoid vasculitis: histological evidence of the involvement of T lymphocytes.

Rheumatoid arthritis (RA) is a chronic joint disease that can be complicated with extra-articular manifestations due to vasculitis. We describe a patient with RA who developed systemic vasculitis and died of myocardial infarction. Autopsy demonstrated vasculitis of the left anterior descendent and circumflex coronary arteries, which were narrowed or occluded with organizing thrombosis. Formation of granuloma with multinucleated giant cells was also observed in media of the circumflex artery. There was no microscopic evidence of atheroma formation in the coronary arteries. Of note, there was a follicle-like infiltration of CD45RO-positive T lymphocytes in interna of the left coronary arteries and the right renal artery. Although not frequently reported, coronary vasculitis as a cause of myocardial infarction should be considered in patients with RA. Moreover, our results suggest that infiltration of T lymphocytes might be involved in the development of rheumatoid vasculitis.

Autoimmune hepatitis in a patient with systemic lupus erythematosus.

We report a female patient with systemic lupus erythematous (SLE), hyperbilirubinemia and high serum value of ALT. International autoimmune hepatitis (AIH) score showed definite AIH before treatment, but autoantibodies could not make a differential diagnosis of AIH and SLE-associated hepatitis. Liver biopsy showed periportal hepatitis with lymphoplasmacytic infiltration, but neither parenchymal collapse nor rosette formation could be found. Pericarditis, pleuritis and nephritis were improved as well as liver injury after administration of prednisolone, and no repeated attack has been present these 4 years. Our case suggested invalidity of AIH score among patients of SLE, and liver histology should be inferred most important at present to make a differential diagnosis of lupus hepatitis or AIH in patients with SLE.

Association of transporter associated with antigen processing genes with Behçet's disease in Japanese.

Contribution of transporter associated with antigen processing (TAP) genes to the pathogenesis of Behçet's disease (BD) was studied. Restriction fragment length polymorphic analysis of TAP genes was carried out in 46 Japanese patients with BD and 95 healthy subjects. There were no significant differences in allele frequencies of TAP1 and TAP2 genes between whole patients with BD and control population. No significant differences in the frequencies of TAP alleles were observed, when patients of BD with complete type or incomplete type were compared with control population, respectively. An allele frequency of TAP2C was, however, slightly but significantly high in patients with BD who had symptom of erythema nodosum (24.1%) as compared to the control group (11.6%). [p < .05, RR = 2.4]. The allele frequency of TAP2C was slightly high in HLA*B5101 positive patients with BD (28.6%) as compared to HLA*B5101 negative patients (10.9%), but the difference did not reach statistical significance. The absence of genotype TAP2B/C was observed in whole patients group, though it was present in control subjects (14.7%). [p = 0.003, RR = 0.06]. A genotype frequency of TAP2C/H was high in patients with BD who had symptom of skin lesions (7.5%) as compared to the control group (0.0%). [p = 0.03, RR = 15.4]. These results suggest the possibility that TAP molecule play some part in formation of skin lesion, such as erythema nodosum in BD in Japanese.

Differential regulation of Th1 responses and CD154 expression in human CD4+ T cells by IFN-alpha.

Like interleukin (IL)-12, interferon (IFN)-alpha has been shown to play an important role in inducing human Th1 responses. Recent studies have shown that human Th1 responses driven by IL-12 are associated with enhanced expression of CD154. The present study examined the effects of IFN-alpha on CD154 expression in human CD4+ T cells, with special attention to the relationship with Th1 responses. Highly purified CD4+ T cells from healthy donors were stimulated with immobilized anti-CD3 with or without IFN-alpha and IL-12 in the complete absence of accessory cells. IFN-alpha suppressed CD154 protein and mRNA expression in CD4+ T cells at the initial phase of activation with immobilized anti-CD3, but enhanced it in the subsequent maturation phase irrespective of the presence of IL-12. By contrast, IFN-alpha by itself did not enhance IFN-gamma production or mRNA expression in CD4+ T cells in the absence of IL-12 even in the presence of stimulation with anti-CD28, but enhanced it in the presence of IL-12. Accordingly, IFN-alpha enhanced IL-12Rbeta2 mRNA expression in anti-CD3-stimulated CD4+ T cells. Neither IFN-alpha nor IL-12 influenced the stability of CD154 mRNA in anti-CD3-activated CD4+ T cells. These results indicate that IFN-alpha by itself enhances CD154 expression in CD4+ T cells independently of the induction of IFN-gamma mRNA expression. The data also suggest that the optimal induction of human Th1 responses by IFN-alpha might require the presence of IL-12 and that the induction of Th1 responses and CD154 expression in human CD4+ T cells might be regulated through different mechanisms.

Increased expression of biglycan mRNA in pressure-overloaded rat heart.

Biglycan mRNA expression in rat myocardium after abdominal aortic banding with renal ischemia was examined. The Northern blot analysis demonstrated that expression of biglycan mRNA in the pressure-overloaded hearts on days 2, 7, 14 and 28 was 2.88 +/- 0.89, 2.32 +/- 0.49, 2.17 +/- 0.57 and 1.81 +/- 0.46-fold higher, respectively, than that in the sham-operated hearts. In situ hybridization showed an increased density of biglycan mRNA signal-positive cells in the pressure-overloaded hearts. The cells with positive signals were spindle-shaped mesenchymal cells in the myocardial interstitium. A marked increase in biglycan mRNA signal expression was also observed in endothelial cells and smooth muscle cells of the thickened myocardial capillary wall. These results demonstrated an increase in biglycan mRNA in the pressure-overloaded heart in mesenchymal cells in the myocardial interstitium, and in endothelial and smooth muscle cells of the capillaries, indicating that biglycan contributes to the ventricular and vascular remodeling in response to pressure overload.

Systemic sclerosis complicated with nephrotic syndrome: relevance with antiribosomal P antibody.

The nephrotic syndrome is an extremely rare occurrence in systemic sclerosis (SSc). Here we describe a 39-year-old woman with SSc who developed the nephrotic syndrome along with the expression of antiribosomal P antibody but not of anti-double-stranded DNA antibody in her serum. Although a renal biopsy specimen showed minimal changes on light microscopy, immunofluorescence studies showed granular deposition of C3 and IgM in the glomeruli. The patient recovered from the nephrotic syndrome with the decrease in serum antiribosomal P antibody after the daily administration of 60 mg of prednisolone. It is strongly suggested that antiribosomal P antibody might have been involved in the development of the nephrotic syndrome in our patient.