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ABSTRACT: Background Because inflammatory cytokines are known to be potent inducers of matrix metalloproteinases (MMPs), and MMPs themselves can promote inflammation, we speculated that MMP activation might be involved in the pathogenesis of Henoch–Schönlein purpura (HSP) vasculitis.Objectives To investigate the gene expression profile of all known MMPs and tissue inhibitors of metalloproteinases (TIMPs) in children with HSP and to examine the role, if any, of MMPs in the pathogenesis of HSP.Methods Peripheral blood samples were obtained from 10 patients with HSP (nine were in the acute stage, one had HSP nephritis) and four healthy controls. Peripheral blood samples were also taken from the nine patients with HSP when they reached the convalescent stage of the disease. From these samples, total RNA was purified and gene expressions were measured using real-time polymerase chain reaction.Results MMP-8 expression was decreased in patients with arthralgia (P = 0·038), and MMP-3 (P = 0·03) and TIMP-4 expressions (P = 0·016) were elevated in HSP patients with nephritis. Soft tissue oedema was associated with decreased expressions of MMP-26 (P = 0·038) and MMP-28 (P = 0·038). MMP-1, MMP-8, MMP-9, MMP-10, MMP-13, MMP-16 and MMP-26 levels were significantly higher in patients in the acute stage of HSP than in normal controls (P < 0·05). MMP-9 (P = 0·097) and MMP-19 (P = 0·054) levels decreased to borderline significance in patients in the convalescent stage compared with those in the acute stage. The duration of steroid administration was negatively correlated with MMP-1, MMP-2, MMP-7, MMP-10, MMP-12, MMP-19, MMP-23 and TIMP-1 levels (P < 0·05), suggesting a suppressive effect of steroids on the expressions of MMPs and TIMPs.Conclusions This is the first study to describe the expression profile of all known MMPs and TIMPs in children with HSP, and our results suggested that abnormal levels of MMP and TIMP activity may have a role in the pathogenesis of HSP.
British Journal of Dermatology 05/2011; 164(6):1348 - 1355. · 3.67 Impact Factor
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ABSTRACT: Because inflammatory cytokines are known to be potent inducers of matrix metalloproteinases (MMPs), and MMPs themselves can promote inflammation, we speculated that MMP activation might be involved in the pathogenesis of Henoch-Schönlein purpura (HSP) vasculitis.
To investigate the gene expression profile of all known MMPs and tissue inhibitors of metalloproteinases (TIMPs) in children with HSP and to examine the role, if any, of MMPs in the pathogenesis of HSP.
Peripheral blood samples were obtained from 10 patients with HSP (nine were in the acute stage, one had HSP nephritis) and four healthy controls. Peripheral blood samples were also taken from the nine patients with HSP when they reached the convalescent stage of the disease. From these samples, total RNA was purified and gene expressions were measured using real-time polymerase chain reaction. Results: MMP-8 expression was decreased in patients with arthralgia (P = 0·038), and MMP-3 (P = 0·03) and TIMP-4 expressions (P = 0·016) were elevated in HSP patients with nephritis. Soft tissue oedema was associated with decreased expressions of MMP-26 (P = 0·038) and MMP-28 (P = 0·038). MMP-1, MMP-8, MMP-9, MMP-10, MMP-13, MMP-16 and MMP-26 levels were significantly higher in patients in the acute stage of HSP than in normal controls (P < 0·05). MMP-9 (P = 0·097) and MMP-19 (P = 0·054) levels decreased to borderline significance in patients in the convalescent stage compared with those in the acute stage. The duration of steroid administration was negatively correlated with MMP-1, MMP-2, MMP-7, MMP-10, MMP-12, MMP-19, MMP-23 and TIMP-1 levels (P < 0·05), suggesting a suppressive effect of steroids on the expressions of MMPs and TIMPs.
This is the first study to describe the expression profile of all known MMPs and TIMPs in children with HSP, and our results suggested that abnormal levels of MMP and TIMP activity may have a role in the pathogenesis of HSP.
British Journal of Dermatology 03/2011; 164(6):1348-55. · 3.67 Impact Factor
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ABSTRACT: To investigate the prevalence and patterns of anti-nuclear antibodies (ANA) in different subtypes of juvenile idiopathic arthritis (JIA) according to the International League of Associations for Rheumatology (ILAR) criteria.
One hundred and fifty-three Korean patients (M:F 83:70) with JIA were followed between 1990 and 2006 and were tested for ANA by an indirect immunofluorescence method using HEp-2 cells as the substrate. ANA tests were repeated in 37 patients during the course of the disease. The median age at onset was 7.5 years (range 0.8-15.9 years).
ANA were positive in 50 (33%) of the 153 patients at a dilution of 1:40 or higher (>1:40 in 70%, >1:80 in 2%, >1:160 in 16%, >1:320 in 2%, and >1:640 in 10%). The patterns of immunofluorescence staining were homogeneous in 50%, speckled in 38%, nucleolar in 8%, and centromere in 4%. ANA titres were decreased in 25 (68%) of the 37 patients, and the nuclear fluorescence patterns changed in 14 (38%) during follow-up. ANA seropositivity was associated with female sex (p<0.0001), negative HLA-B27 (p = 0.01), and a persistently elevated erythrocyte sedimentation rate (ESR) at follow-up (p = 0.014). Furthermore, a high ANA titre (>1:160) was associated with a poor clinical outcome (active patients at follow-up) (p = 0.005).
ANA may be an important marker of disease activity in patients with JIA. ANA titres tend to decrease during disease remission but the fluorescence patterns do not appear to be related to disease activity or clinical outcome.
Scandinavian journal of rheumatology 08/2008; 37(5):348-51. · 2.51 Impact Factor
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Endoscopy 07/2007; 39(6):571; author reply 572. · 5.21 Impact Factor
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Internal Medicine Journal 02/2007; 37(1):69. · 1.54 Impact Factor
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QJM: monthly journal of the Association of Physicians 12/2006; 99(11):801. · 2.33 Impact Factor
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European Journal of Vascular and Endovascular Surgery 10/2006; 32(3):335-6. · 2.99 Impact Factor
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ABSTRACT: We report a child with Henoch-Schönlein purpura (HSP) who had shown persistent microscopic haematuria for 26 months and was found to have nutcracker syndrome by renal Doppler ultrasound. Haematuria subsided in accordance with radiological improvement of nutcracker syndrome. These findings suggest that the origin of urinary abnormalities in patients with HSP may not always be due to the renal involvement of vasculitis.
International Journal of Clinical Practice 01/2006; 59(12):1472-5. · 2.41 Impact Factor
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ABSTRACT: To clarify the role of mesangial fibrinogen deposition in crescentic Henoch-Schönlein nephritis (HSN).
A retrospective analysis of 21 children with HSN treated with immunosuppressants. Serial renal biopsies were performed before and after treatment. They were divided into two groups according to the immunofluorescent course of fibrinogen deposition: group I (n = 9), no or decreased deposition; group II (n = 12), persistent or increased deposition.
There were no differences between the two groups in renal manifestations or laboratory and histological findings at presentation. However, the activity index after immunosuppressive treatment was significantly decreased in group I (mean, 7.9 (SEM, 0.7) v 2.9 (0.4); p = 0.008) and unchanged in group II (mean, 6.8 (SEM, 0.3) v 6.0 (2.1)). The chronicity index was unchanged in group I, but increased in group II (mean, 0.8 (SEM, 0.3) v 1.8 (0.3); p = 0.02). Univariate analysis revealed that the only factor significantly related to persistent or increased fibrinogen deposition was age more than 9 years (p = 0.03). Furthermore, the intensity of fibrinogen deposition at the second biopsy correlated positively with the age at onset (R2= 0.306; p = 0.009) and changes in the percentage of crescents (post-treatment crescents (%) minus pretreatment crescents (%)) correlated positively with the intensity of fibrinogen deposition at the second biopsy (R2= 0.193; p = 0.046).
This study indicates that fibrinogen deposition has an important role to play in renal injury of crescentic HSN and reflects persistent severe histological activity.
Journal of Clinical Pathology 12/2005; 58(11):1147-51. · 2.31 Impact Factor
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Scandinavian Journal of Rheumatology 35(2):162-3. · 2.47 Impact Factor
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ABSTRACT: To identify predictive factors for nephritis, relapse, and significant proteinuria in childhood Henoch-Schönlein purpura (HSP).
Two hundred and six consecutive patients with HSP (93 female, 113 male), followed up at a single centre between 1996 and 2001, were analysed retrospectively. They were regularly monitored for clinical and laboratory parameters for renal sequelae and relapse.
Nephritis was seen in 78 patients (38%), relapse in 52 (25%), and significant proteinuria in 39 (19%). In univariate analysis, an older age at onset (>10 years), persistent purpura, severe bowel angina, and relapse were identified as factors associated with nephritis and significant proteinuria. Relapse-related factors were an older age, persistent purpura, severe bowel angina, and leucocytosis. Logistic regression analysis showed that nephritis was significantly associated with an older age, persistent purpura, and relapse, and significant proteinuria was closely related to severe bowel angina and relapse.
We identified some predictors for nephritis, relapse, and significant proteinuria in childhood HSP, and close attention should be paid to those patients with the risk factors, such as an older age at onset, persistent purpura, severe bowel angina, and relapse.
Scandinavian Journal of Rheumatology 35(1):56-60. · 2.47 Impact Factor
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ABSTRACT: To clarify the therapeutic role of cyclosporin A (CyA) for patients with Henoch-Schönlein purpura nephritis (HSPN) showing nephrotic-range proteinuria.
The clinical and histological findings of eight children (7.7+/-3.8 years), who were treated with CyA and prednisolone, were evaluated retrospectively. All underwent a renal biopsy before therapy, and six of the eight patients received a follow-up biopsy after therapy.
The histological grade of the International Study of Kidney Disease in Children (ISKDC) was improved in all six patients who received a follow-up biopsy (pre-therapy, four grade IIIa and two grade IIIb; post-therapy, one grade I and five grade II) and it was statistically significant (p = 0.031). The activity index was significantly decreased after therapy (8.3+/-1.6 vs. 3.5+/-1.5, p = 0.031), and the chronicity index (0.5+/-0.5 vs. 0.7+/-1.0) and tubulointerstitial (TI) scores (1.5+/-1.3 vs. 0.8+/-1.6) did not change. There was a reduction in proteinuria from 3.2+/-2.3 to 0.1+/-0.1 g/m2/day (p = 0.008) and renal function remained normal in all patients after therapy. However, one patient showed CyA-induced nephrotoxicity at a second biopsy. After an average follow-up period of 3.8 years, six patients showed normal urine and renal function, and two showed minor urinary abnormalities.
This study suggests that CyA therapy is effective in reducing proteinuria, which is a known risk factor for the development of renal insufficiency in HSPN and may regress the renal pathology in patients with nephrotic-range proteinuria.
Scandinavian Journal of Rheumatology 34(5):392-5. · 2.47 Impact Factor
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Clinical and experimental rheumatology 27(6):1054; author reply 1055. · 2.15 Impact Factor
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Scandinavian journal of rheumatology 38(1):73-4; author reply 74-5. · 2.51 Impact Factor
