Yoshiro Horai

Ultrasonographic examination of rheumatoid arthritis patients who are free of physical synovitis: power Doppler subclinical synovitis is associated with bone erosion

OBJECTIVE The aim of this study was to investigate the characteristics of power Doppler (PD) subclinical synovitis in patients with RA who achieve clinical remission free from physical synovitis. METHODS Twenty-nine RA patients were consecutively enrolled. All of the patients had achieved clinical remission [simplified disease activity index (SDAI) 3.3] for at least 6 months at the musculoskeletal ultrasound (MSKUS) examination. Additionally, none of the patients exhibited tender joints at 68 sites or swollen joints at 66 sites. MSKUS of bilateral wrist and finger joints, including the first to fifth MCP joints, the first IP joint and the second to fifth PIP joints, was performed and the findings obtained by grey scale (GS) and PD were graded on a semi-quantitative scale from 0 to 3. RESULTS The median disease duration upon the introduction of DMARDs was 3 months and that at MSKUS examination was 21 months. The percentages of patients with PD synovitis in at least one joint were PD grade 1, 58.6%; PD grade 2, 31.0% and PD grade 3, 6.9%. The use of biological agents was low in patients with PD synovitis grade 2 (P < 0.05). The presence of US bone erosion was high by patient (P < 0.05) and by joint (P < 0.0001) with PD synovitis as compared with those without PD synovitis. However, no correlations were found between PD synovitis measures and serum biomarkers, including angiogenesis factors. CONCLUSION PD subclinical synovitis correlates with several clinical characteristics, whereas conventional serum biomarkers are not useful for indicating the presence of subclinical PD synovitis.

Ultrasonography as an additional item in the American College of Rheumatology classification of Sjögren’s syndrome

OBJECTIVE In this study we evaluated US as an additional classification item in the ACR classification of SS. METHODS Of 581 patients classified as either SS (n = 364) or non-SS (n = 217) based on the minimum requirements of the American-European Consensus Group (AECG) classification, 184 patients (102 SS and 82 non-SS) who had scored two or more positive or two or more negative results according to the ACR criteria were selected. The AECG classification was used as the gold standard. A parotid and/or submandibular gland that was assigned a score ≥G1 was designated as SS positive. We evaluated US alone or with varying combinations of the ACR classification items in the diagnosis of SS. RESULTS The ACR criteria diagnosed the 184 patients with 91% sensitivity, 90% specificity and 91% accuracy. US alone diagnosed the 184 ACR patients with 79% sensitivity, 90% specificity and 83% accuracy, which was comparable to the results of US diagnosis in the AECG cohort (81%, 86% and 83%, respectively). Incorporating the US criteria as an alternative to one of the three ACR classification items achieved 89-91% sensitivity, 87-96% specificity and 89% or 92% accuracy, which was comparable to that of the original ACR classification. Furthermore, kappa analysis indicated that the results of the original ACR and US-replaced ACR classifications matched completely (κ = 0.960-0.974). CONCLUSION These results suggest that US can be used as an alternative to any of the three ACR classification items.

Efficacy and safety of abatacept for patients with Sjögren's syndrome associated with rheumatoid arthritis: Rheumatoid Arthritis with Orencia Trial toward Sjögren's syndrome Endocrinopathy (ROSE) trial—an open-label, one-year, prospective study—Interim analysis of 32 patients for 24 weeks

Abstract Objective. To assess the efficacy and safety of abatacept for secondary Sjögrens syndrome (SS) associated with rheumatoid arthritis (RA). Methods. The primary endpoint of this 1-year, open-labeled, prospective, observational multicenter study of RA-associated secondary SS was the rate of SDAI remission at 52 weeks after initiation of abatacept therapy. The secondary endpoints included that of Saxsons test and Schirmers test. Adverse events during the study period were also analyzed. Results. Thirty-two patients (all females) were enrolled in this study. Interim analysis at 24 weeks included assessment of efficacy (n = 31) and safety (n = 32). The mean SDAI decreased from 19.8 ± 11.0 (± SD) at baseline to 9.9 ± 9.9 at 24 weeks (P < 0.05). Patients with clinical remission, as assessed by SDAI, increased from 0 patient (0 week) to 8 patients (25.8%) at 24 weeks. Saliva volume (assessed by Saxsons test) increased slightly from 2232 ± 1908 (0 week) to 2424 ± 2004 (24 weeks) mg/2 min (n = 29). In 11 patients with Greenspan grading 1/2 of labial salivary glands biopsy, saliva volume increased from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min (P < 0.05). Schirmers test for tear volume showed increase from 3.6 ± 4.6 (0 week) to 5.5 ± 7.1 (24 weeks) mm/5 min (n = 25; P < 0.05). Five adverse events occurred in five of 32 patients (15.6%), and three of these events were infections. Conclusion. Abatacept seems to be effective for both RA and RA-related secondary SS.

Lupus Nephritis IgG Induction of Calcium/Calmodulin-Dependent Protein Kinase IV Expression in Podocytes and Alteration of Their Function

Kidney podocytes and their slit diaphragms prevent urinary protein loss. T cells from patients with systemic lupus erythematosus display increased expression of calcium/calmodulin‐dependent protein kinase IV (CaMKIV). The present study was undertaken to investigate the role of CaMKIV in podocyte function in lupus nephritis (LN).

Serum interferon-α is a useful biomarker in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis

Abstract Objective. We have tried to clarify the clinical importance of the measurement of serum type-I interferon (IFN) in patients with anti-melanoma differentiation-associated gene 5 Ab (MDA5 Ab)-positive dermatomyositis (DM). Methods. We studied 30 patients with DM: 10 were anti-MDA5 Ab-positive and 20 were anti-MDA5 Ab-negative. At each patients initial visit, serum IFN-α, IFN-β, interleukin 18 (IL-18), ferritin, and the titer of anti-MDA5 Ab were measured using enzyme-linked immunosorbent assays (ELISAs). The associations between the IFNs and with the other variables were examined. Results. Rapidly progressive interstitial lung disease (RPILD) was confirmed in 10 patients, most of whom were complicated in the anti-MDA5 Ab-positive DM patients. The presence of clinically amyopathic dermatomyositis (CADM) as well as the serum concentrations of IFN-α and ferritin was significantly higher in the anti-MDA5 Ab-positive DM patients. Serum concentration of IL-18 did not differ between anti-MDA5 Ab-positive and anti-MDA5 Ab-negative groups; however, a positive correlation was found between IFN-α and IL-18 in the anti-MDA5 Ab-positive DM patients (r = 0.8139, p = 0.0146). Conclusion. Serum IFN-α can be used as a useful biomarker in patients with anti-MDA5 Ab-positive DM, which may reflect the presence of RPILD.

Early diagnosis and treatment for remission of clinically amyopathic dermatomyositis complicated by rapid progress interstitial lung disease: a report of two cases

We report two cases of clinically amyopathic dermatomyositis (CADM) complicated by rapid progress interstitial lung disease (RPILD). The diagnosis of CADM was based on Gottron’s papule and RPILD, and the absence of muscle weakness. The female patients were treated with early immunosuppressive therapies including steroid pulse therapy, resulting in significant improvement in respiratory symptoms, clinical data, and imaging. Measurement of anti-CADM-140/MDA5 antibody was useful for obtaining a definitive diagnosis of CADM in these cases.

Synovial inflammation assessed by ultrasonography correlates with MRI-proven osteitis in patients with rheumatoid arthritis

OBJECTIVE The aim of this study was to explore whether assessment of synovial inflammation by ultrasonography correlates with MRI-proven osteitis in patients with RA. METHODS Thirty RA patients who fulfilled 2010 RA classification criteria and were naive to DMARDs, including biologics and glucocorticoids, were consecutively enrolled in this study. Grey scale (GS) and power Doppler (PD) images of articular synovitis and bone erosion in both wrist and MCP joints were evaluated by the method proposed by the European League Against Rheumatism. MRI-proven osteitis of the identical sites was also evaluated within 3 days using the RA MRI scoring system (RAMRIS). The Cochran-Armitage test and Spearmans correlation coefficient were used to investigate the correlation of each US finding with MRI-proven osteitis. RESULTS MRI-proven osteitis was found in 8.3% of MCP joints and 48.3% of wrist joints. Its prevalence was increased in the joints where the GS or PD grade of articular synovitis was 2 or 3. In addition, MRI-proven osteitis was found preferentially in the joints positive for bone erosion on US. A clear correlation was demonstrated between the GS or PD grade of articular synovitis or the presence of US bone erosion and RAMRIS osteitis score in both MCP joints and wrist joints. CONCLUSION Our data indicate that joint injury assessed by US correlates with MRI-proven osteitis in patients with RA.

Lupus nephritis IgG induces the expression of calcium/calmodulin‐dependent kinase type IV in podocytes and alters their function

Kidney podocytes and their slit diaphragms prevent urinary protein loss. T cells from patients with systemic lupus erythematosus display increased expression of calcium/calmodulin‐dependent protein kinase IV (CaMKIV). The present study was undertaken to investigate the role of CaMKIV in podocyte function in lupus nephritis (LN).

Direct Infection of Primary Salivary Gland Epithelial Cells by Human T Lymphotropic Virus Type I in Patients With Sjögren's Syndrome

To investigate whether human T lymphotropic virus type I (HTLV‐I) directly infects salivary gland epithelial cells (SGECs) and induces the niche of the salivary glands in patients with Sjögrens syndrome (SS).

Combination of MRI-detected bone marrow oedema with 2010 rheumatoid arthritis classification criteria improves the diagnostic probability of early rheumatoid arthritis

Efficient methods for distinguishing rheumatoid arthritis (RA) at an earlier phase from other diseases are strongly desired since early therapeutic intervention improves clinical and radiographic outcomes of RA.1–4 The clinical 2010 RA classification criteria was established based upon the consensus that RA is an inflammatory disease that develops persistent and/or erosive arthritis.2 ,3 Our series of studies as well as the article describing European League Against Rheumatism recommendations for the use of imaging for the clinical management of RA mention that MRI can be used to improve the certainty of a diagnosis of RA above clinical criteria.5 ,6 The present study was undertaken to investigate whether MRI findings of wrist and finger joints improve the diagnostic performance of 2010 RA classification criteria. One hundred sixty-six patients with early arthritis, who do not fulfil the 1987 RA criteria or other international criteria for rheumatic disease at entry …