-Hung Chen

Usefulness of human leucocyte antigen-B27 subtypes in predicting ankylosing spondylitis: Taiwan experience

Background:  Genetic factors are clearly attributed to the susceptibility of ankylosing spondylitis (AS). The human leucocyte antigen (HLA)‐B27 proved to be the very useful marker for diagnosing AS. The aim of this study was to determine the prevalence of HLA‐B27 subtypes in Taiwan and to investigate whether these subtypes may be of help in predicting the diagnosis of AS.

Aspirin differentially regulates endotoxin-induced IL-12 and TNF-α production in human dendritic cells

OBJECTIVE In the development of autoimmune diseases, dendritic cells (DC) play critical roles. Here, we examined the effect of aspirin on lipopolysaccharide (LPS)-induced DC activation. METHODS The monocyte-derived DC were established. The cytokine production was measured by ELISA, reverse transcriptase/polymerase chain reaction, or intracellular staining analyzed by flow cytometry. The expression of cell surface molecules was determined by flow cytometry. RESULTS Aspirin inhibited LPS-induced DC maturation and costimulatory molecules expression. Aspirin, at therapeutic concentrations, also decreased LPS-induced IL-12 and IL-10 production. In contrast, the LPS-induced TNF-alpha production was enhanced by aspirin. The differential effects of aspirin on IL-12 and TNF-alpha production may not be due to down-regulation of cyclooxygenase activities. CONCLUSION The various effects of aspirin on LPS-stimulated DC may influence the understanding of the diverse immunomodulatory mechanisms of this anti-inflammatory drug.Objective : In the development of autoimmune diseases, dendritic cells (DC) play critical roles. Here, we examined the effect of aspirin on lipopolysaccharide (LPS)-induced DC activation. Methods : The monocyte-derived DC were established. The cytokine production was measured by ELISA, reverse transcriptase/ polymerase chain reaction, or intracellular staining analyzed by flow cytometry. The expression of cell surface molecules was determined by flow cytometry. Results : Aspirin inhibited LPS-induced DC maturation and costimulatory molecules expression. Aspirin, at therapeutic concentrations, also decreased LPS-induced IL-12 and IL-10 production. In contrast, the LPS-induced TNF- f production was enhanced by aspirin. The differential effects of aspirin on IL-12 and TNF- f production may not be due to down-regulation of cyclooxygenase activities. Conclusion : The various effects of aspirin on LPS-stimulated DC may influence the understanding of the diverse immunomodulatory mechanisms of this anti-inflammatory drug.

Usefulness of erythrocyte-bound C4d as a biomarker to predict disease activity in patients with systemic lupus erythematosus

OBJECTIVE SLE is an autoimmune disorder characterized by abnormal complement activation. Numerous new biomarkers have recently been used to diagnose or monitor disease activity in patients with SLE. We checked the levels of erythrocyte-bound C4d (E-C4d), an activation-derived fragment of C4 that is deposited on the erythrocytes, under different conditions of SLE in order to correlate these levels with disease activity. METHODS We conducted a cross-sectional investigation of three groups of patients: (i) 63 patients with SLE; (ii) 43 patients with other diseases; and (iii) 26 healthy controls. Erythrocytes were analysed by flow cytometry to determine the levels of E-C4d. RESULTS We found a significant elevation in the mean levels of E-C4d in SLE patients compared with patients with other diseases or healthy controls. In SLE patients, the levels of E-C4d were correlated with the SLEDAI and inversely correlated with serum C3/C4 levels. In the subgroup of SLE patients with haemolytic anaemia (HA), a significantly higher level of E-C4d was observed than that in SLE patients without HA. However, in SLE patients with HA, there was no correlation between the levels of E-C4d and other markers of disease activity, including SLEDAI and levels of anti-dsDNA, C3 and C4. CONCLUSION E-C4d levels are useful diagnostic markers for SLE and can serve as biomarkers of disease activity in patients with SLE. However, E-C4d is of limited value in monitoring disease activity in SLE patients with HA.

Systemic lupus erythematosus with simultaneous onset of Kikuchi-Fujimoto’s disease complicated with antiphospholipid antibody syndrome: a case report and review of the literature

Histiocytic necrotizing lymphadenitis, called Kikuchi-Fujimoto’s disease (KFD), is an idiopathic, self-limited condition rarely associated with systemic lupus erythematosus (SLE). The cause of concomitant KFD and SLE is still unknown. We describe a 19-year-old man simultaneously diagnosed with both KFD and SLE complicated with deep vein thrombosis (DVT). To the best of our knowledge, this is the first case report of KFD associated with SLE complicated with antiphospholipid antibody syndrome (APS). Our patient was successfully treated with intravenous pulse methylprednisolone, anticoagulation with heparin, oral hydroxychloroquine, azathioprine, and low-dose aspirin.

Triggering of DC migration by dengue virus stimulation of COX-2-dependent signaling cascades in vitro highlights the significance of these cascades beyond inflammation.

A term “bone‐breaking fever” is used in Chinese medicine to describe the symptoms of patients infected with dengue virus (DV). We examined the significance of the COX‐prostaglandin pathway in human DC infected by DV. We show that DV infection induced the expression of COX‐2 and the production of prostaglandin E2 (PGE2) in DC, and stimulated the DNA binding of NF‐κB and the kinase activity of both IκBα kinase (IKK) α and β. DV infection also activated MAPK and AP‐1 signaling. Both IκBα kinase‐NF‐κB and MAPK‐AP‐1 were upstream of COX‐2 activation. Our investigation into the significance of COX‐2‐PGE2 pathway also revealed that DV infection enhances DC migration by inducing CC chemokine receptor 7 (CCR7) expression, and that blocking COX‐2 or MAPK activity suppresses DV‐induced DC migration. Our data also suggest that PGE2 can induce CCR7 expression on DC and that antagonists of the PGE2 receptors EP2 and EP4 suppress DV‐induced DC migration. We further show that the increased CCR7 expression was observed in both DV‐infected and bystander DC, suggesting the presence of secondary effects in inducing CCR7 expression. Collectively, this study reveals not only the pathways involved in COX‐2 synthesis in DV‐infected DC but also the autocrine action of PGE2 on the migration of DV‐infected DC.

Etanercept as a rescue agent in patient with adult onset Still’s disease complicated with congestive heart failure

Adult onset Still’s disease (AOSD) is an uncommon disorder of unknown cause. The clinical symptoms of AOSD are a spiking fever, a typical rash, arthralgia or arthritis, sore throat, lymphadenopathy, and splenomegaly. Pleuropulmonary and cardiac involvement are rare. We report a patient with a two-year history of AOSD with myocarditis refractory to cyclosporine and glucocorticoid. Significant congestive heart failure due to left ventricle dysfunction and hyperferritinemia developed during the hospital course. After therapy with etanercept, the patient’s clinical manifestations recovered and she regained normal left ventricular systolic function.

Significantly Higher Percentage of Circulating CD27high Plasma Cells in Systemic Lupus Erythematosus Patients with Infection than with Disease Flare-Up

Purpose To distinguish lupus flare-up from infection in systemic lupus erythematosus (SLE), we analyze the expression of circulating CD27high plasma cells in SLE patients with and without infection, in comparison to non-SLE patients with infection. Materials and Methods The percentage of circulating CD27high plasma cells was measured by flow cytometry in the following four groups: 36 SLE patients without infection, 23 SLE patients with infection, eight non-SLE patients with infection, and 26 healthy controls. Results The frequency of CD27high plasma cells had a correlation with the SLE disease activity index (SLEDAI) (r = 0.866, p < 0.05), level of anti-dsDNA (r = 0.886, p < 0.05), C3 (r = - 0.392, p < 0.05), and C4 (r = - 0.337, p < 0.05) in SLE patients without infection, but there was no correlation with disease activity in SLE patients with infection. Among three groups in particular-SLE without infection, SLE with infection, and non-SLE with infection-the percentages of CD27high plasma cells were elevated. The percentage of CD27high plasma cells was higher in SLE patients with infection, when compared to SLE patients without infection. Conclusion The percentage of CD27high plasma cells is a biomarker for disease activity of SLE without infection, under correlation with SLEDAI, anti-dsDNA, and C3 and C4 level. However, when the SLE patients have an infection, the percentage of CD27high plasma cells is not an adequate biomarker for the survey of disease activity. The percentage of CD27high plasma cells may serve as a potential parameter to distinguish a lupus flare-up from infection.

Activin A suppresses interleukin-1-induced matrix metalloproteinase 3 secretion in human chondrosarcoma cells.

The objective was to investigate the effect of activin A on matrix metalloproteinase 3 (MMP-3) production and to identify the role of activin A in chondroprotection. SW1353 cells, a human chondrosarcoma cell line, were stimulated with interleukin (IL) 1α and tumor necrosis factor (TNF) α, and the concentrations of activin A, follistatin, and MMP-3 secreted into the culture media were measured by enzyme-linked immunosorbent assay (ELISA). Activin A was added to cell cultures in the presence of IL-1α or TNFα to determine its effect on the production of MMP-3 and sulfated glycosaminoglycan (sGAG) (measured by Alcian blue assay). To study the mechanism responsible for the chondroprotective effects of activin A, the production of IL-1 receptor antagonist (IL-1ra) and tissue inhibitor for metalloproteinases 1 (TIMP-1) was examined by ELISA. Addition of IL-1α did not affect the production of activin A by cultured SW1353 cells. IL-1α and activin A inhibited the production of follistatin. Stimulation of SW1353 cells with activin A suppressed IL-1α-induced, but not TNFα-induced, MMP-3 expression. Activin A had no effect on the production of sGAG, IL-1ra, or TIMP-1, although it suppressed the induction of TIMP-1 and IL-1ra by IL-1α. This novel finding of MMP-3 inhibition by activin A suggests a new role of activin A in cartilage remodeling. Activin A may have therapeutic potential for preventing cartilage degradation.

A spontaneous intercostal artery hemorrhage in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can lead to damage to several vital organs. Antiphospholipid syndrome (APS), manifesting as vascular thromboembolic events and morbidities of pregnancy in the presence of antiphospholipid antibodies (aPL), has been described in patients with SLE. Catastrophic antiphospholipid syndrome (CAPS), in contradistinction to APS, is defined as three or more organs affected by thrombotic microangiopathy in patients demonstrating aPL and can result in mortality up to 50%. We describe a unique SLE patient who was diagnosed with recurrent APS presented with axillary venous thrombosis and subsequent superficial edema and compartment syndrome. The CAPS followed and revealed thromboses over liver, spleen, and acute pancreatitis. The spontaneous hemorrhage of left fourth intercostal artery (ICA) and left axillary artery occured at the same time without vasculitis or severe trauma. Though emergency transcatheter arterial embolization (TAE) of the left fourth ICA was successfully accomplished by the radiologist. The repeated computed tomography angiogram of chest demonstrated remission of ruptured ICA. Nevertheless, the patient died of diffuse alveolar hemorrhage and respiratory failure and shock. Both disseminated intravascular coagulation (DIC) and CAPS share similar characteristics encompassing thrombotic microangiopathy, bleeding, thromboembolism, and multiple organ dysfunction. It is difficult to distinguish between them, especially in cases such as our uremic SLE patient with a calamitous disease progression. The emphasis of treatment for DIC is on platelet and fresh plasma transfusion, in contrast with anti-coagulant for CAPS. To the best of our knowledge, this is the first report describing ICA hemorrhage in an SLE patient without vasculitis or aneurysm. The lupus flare initiated a pathological immunological cascade and resulted in the CAPS and the vascular damage.

Purtscher’s-like retinopathy as an initial presentation of adult-onset Still’s disease: a case report and review of the literature

Adult-onset Still’s disease is a multisystem inflammatory disorder of unknown etiology and is characterized by high, spiking fever, arthritis, evanescent maculopapular rash, myalgia, serositis, leukocytosis, and involvement of various organs including the eyes. The ocular manifestations have been described including orbital pseudotumor, ptosis, and diplopia with orbital pain but never Purtscher’s-like retinopathy. We describe a 21-year-old male patient with adult-onset Still’s disease who developed the Purtscher’s-like retinopathy. To our knowledge, this is the first reported adult-onset Still’s disease patient with Purtscher’s-like retinopathy as the initial presentation.