Chung-Tei Chou

The effect of etanercept on anti‐cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis

Objective: To evaluate the changes in anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) following etanercept treatment in patients with rheumatoid arthritis. Methods: The study included 90 patients with rheumatoid arthritis who failed treatment with disease modifying antirheumatic drugs (DMARDs). All patients were allowed to continue treatment with DMARDs; 52 of them received etanercept as a twice weekly 25 mg subcutaneous injection for three months, and the others did not. Serum samples were collected at baseline and one month intervals during the treatment course. The serum levels of anti-CCP and RF were tested by enzyme linked immunosorbent assay and nephelometry, respectively. Results: At baseline, 45 of the 52 etanercept treated patients (86.5%) and 32 of the 38 controls (84.2%) were positive for anti-CCP. Tests for RF were positive in 78.9% and 84.2% of patients with or without etanercept treatment, respectively. The serum levels of anti-CCP and RF decreased significantly after a three month etanercept treatment (p = 0.007 and p = 0.006, respectively). The average decrease from baseline calculated for each individual patient in the etanercept treated group was 31.3% for anti-CCP and 36% for RF. The variation in anti-CCP was positively correlated with the variation in disease activity, swollen and tender joint counts, RF, and C reactive protein. Conclusions: Etanercept combined with DMARDs leads to a much greater decrease than DMARDs alone in the serum levels of anti-CCP and RF in rheumatoid arthritis, compatible with a reduction in clinical disease activity.

Association of Bone Morphogenetic Proteins with Spinal Fusion in Ankylosing Spondylitis

Objective. To measure serum concentrations of bone morphogenetic proteins (BMP) in patients with ankylosing spondylitis (AS), and to investigate the relationship between BMP and clinical manifestations and radiographic changes. Methods. We studied 60 consecutive AS patients with and 60 patients without spinal fusion. Spinal radiographs were assessed using the Bath Ankylosing Spondylitis Radiology Index (BASRI) and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Spinal fusion was defined as the presence of total bony bridging between 2 adjacent vertebral bodies in either the lumbar or cervical spine. Serum levels of BMP were determined by enzyme-linked immunosorbent assay. Results. Patients with spinal fusion had higher serum levels of BMP-2 and BMP-4 than either the healthy controls or patients without spinal fusion (p < 0.001), but there was no difference between the latter 2 groups. Serum BMP-7, erythrocyte sedimentation rate, and C-reactive protein (CRP) levels were elevated in patients with spinal fusion compared with those without (p < 0.05). Serum BMP-4 and BMP-7 levels were higher in patients with hip involvement than in those without (p < 0.05). BMP-2 and BMP-4 levels had a significant correlation with spinal radiograph scores, especially for BASRI of the lumbar spine (r = 0.356 and 0.348, respectively, p < 0.001). CRP showed a significant correlation with spine BASRI and mSASSS scores (r = 0.261 and 0.260, respectively, p < 0.05). Conclusion. Rising levels of BMP in AS patients with spinal fusion and the positive correlation between BMP and spinal radiograph scores indicate that BMP may play a role in the process of spinal ankylosis. Serum levels of BMP may reflect radiographic progression of the spine and hip joints.

Predictive and prognostic value of antinuclear antibodies and rheumatoid factor in primary Sjogren’s syndrome

Aims:  To assess the predictive and prognostic value of antinuclear antibodies (ANA) and rheumatoid factor (RF) in primary Sjögren’s syndrome (pSS).

Predictors of Longterm Mortality in Patients with and without Systemic Lupus Erythematosus on Maintenance Dialysis: A Comparative Study

Objective. To compare the prognosis of patients with and without systemic lupus erythematosus (SLE) on dialysis and to determine the factors that affect survival after dialysis. Methods. We used the Taiwan National Health Insurance Research Database (NHRI-NHIRD-99182) and collected data on patients who started maintenance dialysis between 2001 and 2003. Patients were followed from the initiation of dialysis until death, discontinuation of dialysis, or the end of 2008. We did a Kaplan-Meier analysis of the cohort and used multivariate Cox regression analysis to identify significant predictors of survival. Results. Of the 22,394 dialysis patients studied, 303 (1.35%) had SLE. Hypertension and diabetes were the 2 most common comorbidities associated with dialysis for patients with and without SLE. After adjusting for age, sex, dialysis modality, and comorbidities, we found no significant survival difference between the 2 patient groups after 8 years of followup. Multivariate analysis showed that increased mortality in the patient group without SLE (p < 0.05) was associated with older age (≥ 45 years), male sex, initial choice of hemodialysis, diabetes mellitus, heart failure, coronary artery disease, cerebrovascular disease, and malignancy. In the patient group with SLE, independent predictors of mortality (p < 0.05) were older age (≥ 65 years), male sex, and diabetes mellitus. Conclusion. The longterm survival outcome was similar between patients with and without SLE who were on dialysis. The factors affecting patient mortality were not identical in these 2 groups.

Polyclonal anticardiolipin antibodies purified from sera of patients with active systemic lupus erythematosus induce apoptosis of the cultured glomerular mesangial cells

Objective: To test the effect of anticardiolipin antibodies (aCL) on cultured glomerular mesangial cells with regard to their expression of apoptosis-related genes. Methods: aCL puri®ed from active lupus sera by cardiolipin micelles were incubated with cultured rodent mesangial cells (RMC). Morphological changes of the RMC were observed. The genomic DNA was extracted for the detection of apoptosis. The total cell RNA was extracted for detection of Fas, c-myc, p53, and bcl-2 transcripts by reverse transcription-polymerase chain reaction. Results: aCL (100 GPL-U/0.1 mg protein/ml) bound to RMC more prominent than human IgG (100mg/ml). The antibodies suppressed RMC proliferation in a dose-dependent manner. The RMC were undergoing apoptosis as evidenced by morphologic changes, ̄uoresceinannexin V staining and appearance of nucleosome-sized DNA fragments. RMC spontaneously express p53 and c-myc but not Fas or bcl-2. aCL (100 GPL-U/ml) enhanced the expression of Fas but not other apoptosis-related genes and suppressed the intracellular tyrosine phosphorylation. Conclusions: Binding of aCL can induce apoptosis of the RMC. The aCL may be implicated in the pathogenesis of lupus nephritis.OBJECTIVE To test the effect of anticardiolipin antibodies (aCL) on cultured glomerular mesangial cells with regard to their expression of apoptosis-related genes. METHODS aCL purified from active lupus sera by cardiolipin micelles were incubated with cultured rodent mesangial cells (RMC). Morphological changes of the RMC were observed. The genomic DNA was extracted for the detection of apoptosis. The total cell RNA was extracted for detection of Fas, c-myc, p53, and bcl-2 transcripts by reverse transcription-polymerase chain reaction. RESULTS aCL (100 GPL-U/0.1 mg protein/ml) bound to RMC more prominent than human IgG (100 microg/ml). The antibodies suppressed RMC proliferation in a dose-dependent manner. The RMC were undergoing apoptosis as evidenced by morphologic changes, fluoresceinannexin V staining and appearance of nucleosome-sized DNA fragments. RMC spontaneously express p53 and c-myc but not Fas or bcl-2. aCL (100 GPL-U/ml) enhanced the expression of Fas but not other apoptosis-related genes and suppressed the intracellular tyrosine phosphorylation. CONCLUSIONS Binding of aCL can induce apoptosis of the RMC. The aCL may be implicated in the pathogenesis of lupus nephritis.

A large ulcer and cutaneous small‐vessel vasculitis associated with syphilis infection

Cutaneous vasculitis (CV) is a condition with cutaneous manifestations and possible systemic involvement. The causative factors or associated diseases are usually drugs, infection, collagen vascular disease, or malignancy. Syphilis as a cause of cutaneous vasculitis is rare. We report the case of a large cutaneous ulcer and small‐vessel vasculitis associated with syphilis infection. We suggest that in apparently idiopathic CV or a chronic ulcer refractory to treatment, screening should be performed to detect any underlying infection such as syphilis. It is important to have a rapid and accurate diagnosis because the lesions are very contagious, but may be rapidly and completely cured by early administration of antibiotic treatment.

Severe atlantoaxial subluxation in early ankylosing spondylitis.

T he patient was a 23-year-old man who had a diagnosis of ankylosing spondylitis (AS) under nonsteroidal antiinflammatory drugs and sulfasalazine (salazopyrin) treatment 3 years ago. Six months ago, he began to have progressive limited range of motion over cervical spine and intermittent left-arm numbness. Radiographic finding showed bilateral grade 2 sacroiliitis without significant syndesmophytes of the lumbar spine. Plain cervical radiographs showed severe atlantoaxial subluxation (AAS) about 20 mm in width (Fig.).

Protein losing enteropathy and premature ovarian failure in a young woman with systemic lupus erythematosus

Protein-losing enteropathy (PLE) and autoimmune oophoritis are unusual manifestations of systemic lupus erythematosus (SLE). Autoimmune oophoritis may result in menstrual disturbance and spontaneous premature ovarian failure. However, there is no validated examination to confirm the diagnosis and it is easily neglected in patients with ovarian insufficiency. A 31-year-old woman with SLE presented with PLE and autoimmune oophoritis during the long course of flares and remissions in her lupus activity. The synchronism implied the association between the two. Moreover, both conditions simultaneously had a good response to cyclosporine A (CsA) therapy.

Incidence and antiviral response of hepatitis C virus reactivation in lupus patients undergoing immunosuppressive therapy

Objective Systemic lupus erythematosus (SLE) is a systemic autoimmune disease and usually requires immunosuppressive therapy, which is a major cause of viral reactivation. The incidence and antiviral response in SLE patients with hepatitis C virus (HCV) reactivation is unclear and needs to be investigated. Methods One hundred and sixty-six SLE patients with antibody to HCV (anti-HCV) status were retrospectively reviewed regarding the events of HCV reactivation. Patients with HCV reactivation were treated with pegylated interferon plus ribavirin treatment. The virological response and relapse rate were evaluated. Results Twenty-six patients were positive for anti-HCV. During a mean 8.4 years of follow-up, 10 (38.5%) cases developed HCV reactivation. No clear relationship was noted between immunosuppressive therapy and the HCV reactivation. Eight patients underwent antiviral therapy and the rapid virological response (RVR), early virological response, and sustained virological response (SVR) rates were 37.5%, 87.5%, and 75.0%, respectively. However, late relapse (reappearance of HCV RNA in serum after archiving SVR) was found in two (33.3%) of six patients achieving SVR. The two cases were HCV genotype 1 b concurrent with corticosteroid treatment. Conclusions HCV reactivation in anti-HCV-positive SLE patients was possibly associated with glucocorticoids. The virological response to interferon plus ribavirin treatment is not inferior to the general population. However, monitoring HCV RNA after SVR is necessary for patients concurrent with corticosteroid treatment due to the risk of late relapse.

Why is biologic therapy useful in spondyloarthritis? Knowledge from synovial immunopathologic studies of spondyloarthritis.

The pathogenesis of most rheumatic diseases remains unknown. It is believed that both genetic and environmental factors play a pivotal role in the development of synovial inflammation in rheumatoid arthritis (RA), spondyloarthritis (SpA) and osteoarthritis (OA). In the last two decades, there have been many immunopathologic studies on RA, SpA and OA, and the findings revealed different types of arthritis may also present different pathologic patterns. These included higher vascularity and increased infiltration with CD163 macrophages and neutrophils, but relatively low values for lining cell (LL) hyperplasia in SpA synovium. However, the increased LL hyperplasia, as well as CD1a+ cells and the presence of intracellular citrullinated protein were more prominent in RA than in SpA synovitis. Anti‐tumor necrosis factor alpha (anti‐TNFα) therapy can significantly reduce synovial LL hyperplasia, vascularity and mononuclear cells infiltration in the majority of RA or SpA patients. This may explain why clinically, arthritis patients can get significant improvement after TNFα blocker treatment.