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T. Hashimoto - One of the best experts on this subject based on the ideXlab platform.

  • thu0190 ultrasonagraphic assessment of submandibular glands in anti Centromere Antibody positive and negative primary sjogren s syndrome patients
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, S. Uchiyama, Masayasu Kitano, T. Iwasaki, Hajime Sano, T. Hashimoto
    Abstract:

    Background Primary Sjogren’s Syndrome (pSS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration into exocrine glands. Previous reports have demonstrated that a subgroup of anti-Centromere Antibody (ACA) positive pSS (ACA+/pSS) represents intermediate features between ACA negative pSS (ACA-/pSS) and limited cutaneous systemic sclerosis. ACA+/pSS patients had a higher prevalence of Raynoud’s phenomenon, primary biliary cirrhosis (PBC) and fibrotic change of minor salivary glands compared to ACA-/pSS patients. Objectives We previously reported that submandibular gland (SG) ultrasonagraphy (US) is a useful noninvasive and inexpensive procedure for the evaluation of the morphological changes of salivary gland involvement in pSS patients (International Symposium on Sjogren’s Syndrome 2002, EULAR 2009). In the present study, we evaluated SG by using US in ACA+/pSS and ACA-/pSS patients. Methods Twenty ACA+/pSS and 30 ACA-/pSS patients were studied. SG involvement was evaluated by a single blinded observer using US staging (range 1 to 4) that assigns points to the glandular size, different degree of glandular inhomogeneity and contrast of SG to diagastric muscle. The pulsatility index (PI) and resistance index (RI) were calculated by the pulsed wave traces by power Doppler US at the internal SG facial arteries. All pSS patients were evaluated for the presence of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, Raynoud’s phenomenon, cutaneous manifestation, PBC and joint involvement. We also analyzed ACA, anti-SS-A antibodies, anti-SS-B antibodies, anti-M2 antibodies, rheumatoid factor (RF) and γ-globulin in serum from pSS patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 Antibody and histopathological findings. Results ACA+/pSS and ACA-/pSS subgroup did not differ in median age and the amount of whole saliva by gum test. The immunological parameters (anti-SS-A antibodies, anti-SS-B antibodies, RF and hyper γ-globulinemia) showed no significant differences between these subgroups. The prevalences of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, cutaneous manifestation and joint involvement showed no differences between theses subgroups. However, the prevalence of PBC was significantly higher in ACA+/pSS patients than in ACA-/pSS patients (25.0% vs 3.3%, p=0.02). The prevalence of Raynoud’s phenomenon was tended to be higher in ACA+/pSS patients compared to ACA-/pSS patients (p=0.06). The US staging score was not significantly different between these subgroups (ACA+pSS; 2.45±1.1 vs ACA-pSS; 1.97±1.1), although the size of SG was significantly smaller in ACA+pSS than in ACA-pSS patients (203.0±76.0 vs 261.2±94.0 mm 2 , p Conclusions By using US, we observed a higher prevalence of SG atrophy and low blood flow in ACA+/pSS patients as compared to ACA-/pSS patients. US assessment may be useful to evaluate the differences of histopathological changes of salivary glands between ACA+/pSS and ACA-/pSS patients. Disclosure of Interest None Declared

  • THU0190 Ultrasonagraphic assessment of submandibular glands in anti-Centromere Antibody positive and negative primary sjogren’s syndrome patients
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, S. Uchiyama, Masayasu Kitano, T. Iwasaki, Hajime Sano, T. Hashimoto
    Abstract:

    Background Primary Sjogren’s Syndrome (pSS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration into exocrine glands. Previous reports have demonstrated that a subgroup of anti-Centromere Antibody (ACA) positive pSS (ACA+/pSS) represents intermediate features between ACA negative pSS (ACA-/pSS) and limited cutaneous systemic sclerosis. ACA+/pSS patients had a higher prevalence of Raynoud’s phenomenon, primary biliary cirrhosis (PBC) and fibrotic change of minor salivary glands compared to ACA-/pSS patients. Objectives We previously reported that submandibular gland (SG) ultrasonagraphy (US) is a useful noninvasive and inexpensive procedure for the evaluation of the morphological changes of salivary gland involvement in pSS patients (International Symposium on Sjogren’s Syndrome 2002, EULAR 2009). In the present study, we evaluated SG by using US in ACA+/pSS and ACA-/pSS patients. Methods Twenty ACA+/pSS and 30 ACA-/pSS patients were studied. SG involvement was evaluated by a single blinded observer using US staging (range 1 to 4) that assigns points to the glandular size, different degree of glandular inhomogeneity and contrast of SG to diagastric muscle. The pulsatility index (PI) and resistance index (RI) were calculated by the pulsed wave traces by power Doppler US at the internal SG facial arteries. All pSS patients were evaluated for the presence of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, Raynoud’s phenomenon, cutaneous manifestation, PBC and joint involvement. We also analyzed ACA, anti-SS-A antibodies, anti-SS-B antibodies, anti-M2 antibodies, rheumatoid factor (RF) and γ-globulin in serum from pSS patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 Antibody and histopathological findings. Results ACA+/pSS and ACA-/pSS subgroup did not differ in median age and the amount of whole saliva by gum test. The immunological parameters (anti-SS-A antibodies, anti-SS-B antibodies, RF and hyper γ-globulinemia) showed no significant differences between these subgroups. The prevalences of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, cutaneous manifestation and joint involvement showed no differences between theses subgroups. However, the prevalence of PBC was significantly higher in ACA+/pSS patients than in ACA-/pSS patients (25.0% vs 3.3%, p=0.02). The prevalence of Raynoud’s phenomenon was tended to be higher in ACA+/pSS patients compared to ACA-/pSS patients (p=0.06). The US staging score was not significantly different between these subgroups (ACA+pSS; 2.45±1.1 vs ACA-pSS; 1.97±1.1), although the size of SG was significantly smaller in ACA+pSS than in ACA-pSS patients (203.0±76.0 vs 261.2±94.0 mm 2 , p Conclusions By using US, we observed a higher prevalence of SG atrophy and low blood flow in ACA+/pSS patients as compared to ACA-/pSS patients. US assessment may be useful to evaluate the differences of histopathological changes of salivary glands between ACA+/pSS and ACA-/pSS patients. Disclosure of Interest None Declared

  • AB0502 Long-term follow-up of esophageal diameter in patients with anti-Centromere Antibody sero-positive systemic sclerosis and primary sjögren’s syndrome
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, Masayasu Kitano, T. Iwasaki, Hajime Sano, H. Kuno, T. Hashimoto
    Abstract:

    Background Anti-Centromere antibodies (ACA) are characteristic autoantibodies which are detected in patients with systemic sclerosis (SSc) and primary Sjogren’s syndrome (pSS). We previously reported that ACA are a useful marker of esophageal dilatation in patients with SSc (EULAR2010). Objectives The aim of this study was to examine the role of ACA for esophageal dysfunction in patients with SSc and pSS using the barium esophagogram during long-term follow up. Methods Twelve ACA sero-positive pSS (ACA+/pSS) and 20 ACA sero-positive SSc (ACA+/SSc) patients were studied. Barium esophagogram was performed in all ACA+/pSS and ACA+/SSc patients by receiving 4 successive swallows of 20 ml of barium at 30 sec intervals in the standing position. The esophageal dilatation was examined by measurement of maximal diameters at lower esophagus by a single blinded observer. All ACA+/pSS and ACA+/SSc patients were evaluated for the presence of cutaneous subtype, interstitial pneumonia, joint involvement, chronic thyroiditis, primary biliary cirrhosis (PBC) and Raynoud’s phenomenon. We also analyzed γ-globulin, rheumatoid factor (RF), anti-SS-A antibodies, anti-SS-B antibodies, anti-Topoisomerase I antibodies (Topo-I) and anti-U1 RNP antibodies in serum from all patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 antibodies and histopathological findings. Results All ACA+/pSS and ACA+/SSc patients were women. Follow-up period (6.88±1.98 vs 7.14±1.63 years) and median age (64.8±11.2 vs 59.5±10.6 years) were not different between ACA+/pSS and ACA+/SSc patients. There was no significant difference between ACA+/pSS and ACA+/SSc patients in the prevalence of interstitial pneumonia, joint involvement, chronic thyroiditis, PBC, hyper γ-globulinemia and positivity of RF. However, the prevalence of anti-SS-A Antibody and anti-SS-B Antibody sero-positive patients were significantly higher in ACA+/pSS than in ACA+/SSc (66.7% vs 20.0%, p=0.008, 25.0 vs 0.0%, p=0.019). Anti-Topo-I antibodies and anti-U1 RNP antibodies were not detected in all patients. Although the esophageal diameters were not significantly different between these groups at the initial evaluation (22.1±2.5mm vs 26.6±8.4mm), they were significantly wider in ACA+/SSc patients than in ACA+/pSS patients at the end of follow-up (21.1±4.1mm vs 30.8±10.5mm, p=0.005). In addition, ACA+/SSc patients showed significant increase of the percentage change of esophageal diameters during follow-up when compared with ACA+/pSS patients (95.3% vs 119.5%, p=0.047). Conclusions The present study demonstrated that esophageal dilatation was progressive in ACA sero-positive patients during long-term follow-up. However, the severity of esophageal dilatation depended on the underlying diseases. Another factor other than ACA seems to contribute to esophageal dysfunction. Disclosure of Interest None Declared

Naoaki Hashimoto - One of the best experts on this subject based on the ideXlab platform.

  • thu0190 ultrasonagraphic assessment of submandibular glands in anti Centromere Antibody positive and negative primary sjogren s syndrome patients
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, S. Uchiyama, Masayasu Kitano, T. Iwasaki, Hajime Sano, T. Hashimoto
    Abstract:

    Background Primary Sjogren’s Syndrome (pSS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration into exocrine glands. Previous reports have demonstrated that a subgroup of anti-Centromere Antibody (ACA) positive pSS (ACA+/pSS) represents intermediate features between ACA negative pSS (ACA-/pSS) and limited cutaneous systemic sclerosis. ACA+/pSS patients had a higher prevalence of Raynoud’s phenomenon, primary biliary cirrhosis (PBC) and fibrotic change of minor salivary glands compared to ACA-/pSS patients. Objectives We previously reported that submandibular gland (SG) ultrasonagraphy (US) is a useful noninvasive and inexpensive procedure for the evaluation of the morphological changes of salivary gland involvement in pSS patients (International Symposium on Sjogren’s Syndrome 2002, EULAR 2009). In the present study, we evaluated SG by using US in ACA+/pSS and ACA-/pSS patients. Methods Twenty ACA+/pSS and 30 ACA-/pSS patients were studied. SG involvement was evaluated by a single blinded observer using US staging (range 1 to 4) that assigns points to the glandular size, different degree of glandular inhomogeneity and contrast of SG to diagastric muscle. The pulsatility index (PI) and resistance index (RI) were calculated by the pulsed wave traces by power Doppler US at the internal SG facial arteries. All pSS patients were evaluated for the presence of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, Raynoud’s phenomenon, cutaneous manifestation, PBC and joint involvement. We also analyzed ACA, anti-SS-A antibodies, anti-SS-B antibodies, anti-M2 antibodies, rheumatoid factor (RF) and γ-globulin in serum from pSS patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 Antibody and histopathological findings. Results ACA+/pSS and ACA-/pSS subgroup did not differ in median age and the amount of whole saliva by gum test. The immunological parameters (anti-SS-A antibodies, anti-SS-B antibodies, RF and hyper γ-globulinemia) showed no significant differences between these subgroups. The prevalences of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, cutaneous manifestation and joint involvement showed no differences between theses subgroups. However, the prevalence of PBC was significantly higher in ACA+/pSS patients than in ACA-/pSS patients (25.0% vs 3.3%, p=0.02). The prevalence of Raynoud’s phenomenon was tended to be higher in ACA+/pSS patients compared to ACA-/pSS patients (p=0.06). The US staging score was not significantly different between these subgroups (ACA+pSS; 2.45±1.1 vs ACA-pSS; 1.97±1.1), although the size of SG was significantly smaller in ACA+pSS than in ACA-pSS patients (203.0±76.0 vs 261.2±94.0 mm 2 , p Conclusions By using US, we observed a higher prevalence of SG atrophy and low blood flow in ACA+/pSS patients as compared to ACA-/pSS patients. US assessment may be useful to evaluate the differences of histopathological changes of salivary glands between ACA+/pSS and ACA-/pSS patients. Disclosure of Interest None Declared

  • THU0190 Ultrasonagraphic assessment of submandibular glands in anti-Centromere Antibody positive and negative primary sjogren’s syndrome patients
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, S. Uchiyama, Masayasu Kitano, T. Iwasaki, Hajime Sano, T. Hashimoto
    Abstract:

    Background Primary Sjogren’s Syndrome (pSS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration into exocrine glands. Previous reports have demonstrated that a subgroup of anti-Centromere Antibody (ACA) positive pSS (ACA+/pSS) represents intermediate features between ACA negative pSS (ACA-/pSS) and limited cutaneous systemic sclerosis. ACA+/pSS patients had a higher prevalence of Raynoud’s phenomenon, primary biliary cirrhosis (PBC) and fibrotic change of minor salivary glands compared to ACA-/pSS patients. Objectives We previously reported that submandibular gland (SG) ultrasonagraphy (US) is a useful noninvasive and inexpensive procedure for the evaluation of the morphological changes of salivary gland involvement in pSS patients (International Symposium on Sjogren’s Syndrome 2002, EULAR 2009). In the present study, we evaluated SG by using US in ACA+/pSS and ACA-/pSS patients. Methods Twenty ACA+/pSS and 30 ACA-/pSS patients were studied. SG involvement was evaluated by a single blinded observer using US staging (range 1 to 4) that assigns points to the glandular size, different degree of glandular inhomogeneity and contrast of SG to diagastric muscle. The pulsatility index (PI) and resistance index (RI) were calculated by the pulsed wave traces by power Doppler US at the internal SG facial arteries. All pSS patients were evaluated for the presence of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, Raynoud’s phenomenon, cutaneous manifestation, PBC and joint involvement. We also analyzed ACA, anti-SS-A antibodies, anti-SS-B antibodies, anti-M2 antibodies, rheumatoid factor (RF) and γ-globulin in serum from pSS patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 Antibody and histopathological findings. Results ACA+/pSS and ACA-/pSS subgroup did not differ in median age and the amount of whole saliva by gum test. The immunological parameters (anti-SS-A antibodies, anti-SS-B antibodies, RF and hyper γ-globulinemia) showed no significant differences between these subgroups. The prevalences of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, cutaneous manifestation and joint involvement showed no differences between theses subgroups. However, the prevalence of PBC was significantly higher in ACA+/pSS patients than in ACA-/pSS patients (25.0% vs 3.3%, p=0.02). The prevalence of Raynoud’s phenomenon was tended to be higher in ACA+/pSS patients compared to ACA-/pSS patients (p=0.06). The US staging score was not significantly different between these subgroups (ACA+pSS; 2.45±1.1 vs ACA-pSS; 1.97±1.1), although the size of SG was significantly smaller in ACA+pSS than in ACA-pSS patients (203.0±76.0 vs 261.2±94.0 mm 2 , p Conclusions By using US, we observed a higher prevalence of SG atrophy and low blood flow in ACA+/pSS patients as compared to ACA-/pSS patients. US assessment may be useful to evaluate the differences of histopathological changes of salivary glands between ACA+/pSS and ACA-/pSS patients. Disclosure of Interest None Declared

  • AB0502 Long-term follow-up of esophageal diameter in patients with anti-Centromere Antibody sero-positive systemic sclerosis and primary sjögren’s syndrome
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, Masayasu Kitano, T. Iwasaki, Hajime Sano, H. Kuno, T. Hashimoto
    Abstract:

    Background Anti-Centromere antibodies (ACA) are characteristic autoantibodies which are detected in patients with systemic sclerosis (SSc) and primary Sjogren’s syndrome (pSS). We previously reported that ACA are a useful marker of esophageal dilatation in patients with SSc (EULAR2010). Objectives The aim of this study was to examine the role of ACA for esophageal dysfunction in patients with SSc and pSS using the barium esophagogram during long-term follow up. Methods Twelve ACA sero-positive pSS (ACA+/pSS) and 20 ACA sero-positive SSc (ACA+/SSc) patients were studied. Barium esophagogram was performed in all ACA+/pSS and ACA+/SSc patients by receiving 4 successive swallows of 20 ml of barium at 30 sec intervals in the standing position. The esophageal dilatation was examined by measurement of maximal diameters at lower esophagus by a single blinded observer. All ACA+/pSS and ACA+/SSc patients were evaluated for the presence of cutaneous subtype, interstitial pneumonia, joint involvement, chronic thyroiditis, primary biliary cirrhosis (PBC) and Raynoud’s phenomenon. We also analyzed γ-globulin, rheumatoid factor (RF), anti-SS-A antibodies, anti-SS-B antibodies, anti-Topoisomerase I antibodies (Topo-I) and anti-U1 RNP antibodies in serum from all patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 antibodies and histopathological findings. Results All ACA+/pSS and ACA+/SSc patients were women. Follow-up period (6.88±1.98 vs 7.14±1.63 years) and median age (64.8±11.2 vs 59.5±10.6 years) were not different between ACA+/pSS and ACA+/SSc patients. There was no significant difference between ACA+/pSS and ACA+/SSc patients in the prevalence of interstitial pneumonia, joint involvement, chronic thyroiditis, PBC, hyper γ-globulinemia and positivity of RF. However, the prevalence of anti-SS-A Antibody and anti-SS-B Antibody sero-positive patients were significantly higher in ACA+/pSS than in ACA+/SSc (66.7% vs 20.0%, p=0.008, 25.0 vs 0.0%, p=0.019). Anti-Topo-I antibodies and anti-U1 RNP antibodies were not detected in all patients. Although the esophageal diameters were not significantly different between these groups at the initial evaluation (22.1±2.5mm vs 26.6±8.4mm), they were significantly wider in ACA+/SSc patients than in ACA+/pSS patients at the end of follow-up (21.1±4.1mm vs 30.8±10.5mm, p=0.005). In addition, ACA+/SSc patients showed significant increase of the percentage change of esophageal diameters during follow-up when compared with ACA+/pSS patients (95.3% vs 119.5%, p=0.047). Conclusions The present study demonstrated that esophageal dilatation was progressive in ACA sero-positive patients during long-term follow-up. However, the severity of esophageal dilatation depended on the underlying diseases. Another factor other than ACA seems to contribute to esophageal dysfunction. Disclosure of Interest None Declared

Mitsuhiro Kawano - One of the best experts on this subject based on the ideXlab platform.

  • Impact of double positive for anti-Centromere and anti-SS-a/Ro antibodies on clinicopathological characteristics of primary Sjögren's syndrome: a retrospective cohort study.
    Modern rheumatology, 2018
    Co-Authors: Yasunori Suzuki, Hiroshi Fujii, Ichiro Mizushima, Kazunori Yamada, Hideki Nomura, Masakazu Yamagishi, Mitsuhiro Kawano
    Abstract:

    Objectives: The purpose of our study was to define the clinical characteristics of anti-Centromere Antibody and anti-SS-A/Ro Antibody (ACA/SS-A) double positive Sjogren’s syndrome (SS) and to clari...

  • SAT0031 Clinicopathological Characteristics of Anti-Centromere Antibody- And/Or Anti-Ssa Antibody-Positive SjÖGren's Syndrome
    Annals of the Rheumatic Diseases, 2014
    Co-Authors: Yasunori Suzuki, Hiroshi Fujii, Ryoko Hamano, Ichiro Mizushima, Kazunori Yamada, Mitsuhiro Kawano
    Abstract:

    Background Several small clinical studies have reported that anti-Centromere Antibody (ACA)-positive Sjogren9s syndrome (SS) differs from anti-SSA Antibody (SSA)-positive SS in some clinical points [1,2]). However, the clinical role of ACA in SS is still unclear. To study the clinical features of ACA-positive SS, 3 groups should be compared; ACA-positive and SSA-positive SS (ACA+SSA+ group), ACA-negative and SSA-positive SS (ACA-SSA+ group), and ACA-positive and SSA-negative SS (ACA+SSA- group). However no reports have ever been designed to compare these 3 groups. There are no reports about ACA+SSA+ SS either. Objectives We aimed to examine the clinical role of ACA in SS by clarifying the clinicopathological features of ACA- and/or SSA-positive SS. Methods We evaluated 15 patients with ACA+SSA+ SS, 67 patients with ACA-SSA+ SS, and 24 patients with ACA+SSA- SS. All patients met the Japanese Ministry of Health revised criteria (1999) and/or the American College of Rheumatology classification criteria (2012). Patients who had collagen diseases other than systemic sclerosis and had a low titer of SSA were excluded. We performed minor labial salivary gland biopsy in all patients, evaluated focus scores, and compared the clinicopathological data of these 3 groups. Serum levels of many cytokines were also estimated using multiplex assays. In the assays, patients who were being treated with corticosteroid were excluded. Results In the 2 ACA-positive groups, age at onset of SS and positive rate for Raynaud9s phenomenon were higher than those of ACA-SSA+ SS. Sclerodactyly was observed in 13.3% of the ACA+SSA+ group, 37.5% of the ACA+SSA- group, and none of the ACA-SSA+ group. No patient developed new skin sclerosis during the follow-up period of mean 40 months. Follow-up period did not significantly differ among the 3 groups. Saxon9s test in the ACA+SSA+ group was lower than that in the ACA-SSA+ group (0.43±0.35 vs 1.39±1.55 g, p=0.009). The 2 SSA-positive groups had lymphocytopenia and high serum IgG levels. The focus scores and fibrosis of the biopsy specimens did not differ significantly. Two ACA+SSA+ patients had pulmonary arterial hypertension. Other extraglandular involvement including malignant lymphoma showed no significant differences in the 3 groups. Serum IL-12 was high in the ACA+SSA+ group, while IFN-γ was high in the 2 SSA-positive groups. Conclusions Clinicopathological data and serum cytokine profile in the 3 groups differed. Although the 2 ACA-positive groups had some features of systemic sclerosis such as Raynaud9s phenomenon, not many patients showed sclerodactyly at diagnosis and no patient developed new skin sclerosis during the follow-up. The ACA+SSA+ group may be more likely to have features of SS than those of systemic sclerosis because they showed a lower salivary flow rate in Saxon9s test than that in the ACA-SSA+ SS which was typical SS. Serum IL-12 was high in the ACA+SSA+ group, and there are reports that IL-12 transgenic mice mimic human Sjogren9s syndrome [3]. Thus, measuring ACA is an important component in the management of SS. References J Rheumatol 2001;28:2238-44. J Autoimmun 2012;39:15-26. Arthritis Rheum 2009;60:3633-41. Acknowledgements We thank John Gelblum for his critical reading of the manuscript. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3149

  • sat0031 clinicopathological characteristics of anti Centromere Antibody and or anti ssa Antibody positive sjogren s syndrome
    Annals of the Rheumatic Diseases, 2014
    Co-Authors: Yasunori Suzuki, Hiroshi Fujii, Ryoko Hamano, Ichiro Mizushima, Kazunori Yamada, Mitsuhiro Kawano
    Abstract:

    Background Several small clinical studies have reported that anti-Centromere Antibody (ACA)-positive Sjogren9s syndrome (SS) differs from anti-SSA Antibody (SSA)-positive SS in some clinical points [1,2]). However, the clinical role of ACA in SS is still unclear. To study the clinical features of ACA-positive SS, 3 groups should be compared; ACA-positive and SSA-positive SS (ACA+SSA+ group), ACA-negative and SSA-positive SS (ACA-SSA+ group), and ACA-positive and SSA-negative SS (ACA+SSA- group). However no reports have ever been designed to compare these 3 groups. There are no reports about ACA+SSA+ SS either. Objectives We aimed to examine the clinical role of ACA in SS by clarifying the clinicopathological features of ACA- and/or SSA-positive SS. Methods We evaluated 15 patients with ACA+SSA+ SS, 67 patients with ACA-SSA+ SS, and 24 patients with ACA+SSA- SS. All patients met the Japanese Ministry of Health revised criteria (1999) and/or the American College of Rheumatology classification criteria (2012). Patients who had collagen diseases other than systemic sclerosis and had a low titer of SSA were excluded. We performed minor labial salivary gland biopsy in all patients, evaluated focus scores, and compared the clinicopathological data of these 3 groups. Serum levels of many cytokines were also estimated using multiplex assays. In the assays, patients who were being treated with corticosteroid were excluded. Results In the 2 ACA-positive groups, age at onset of SS and positive rate for Raynaud9s phenomenon were higher than those of ACA-SSA+ SS. Sclerodactyly was observed in 13.3% of the ACA+SSA+ group, 37.5% of the ACA+SSA- group, and none of the ACA-SSA+ group. No patient developed new skin sclerosis during the follow-up period of mean 40 months. Follow-up period did not significantly differ among the 3 groups. Saxon9s test in the ACA+SSA+ group was lower than that in the ACA-SSA+ group (0.43±0.35 vs 1.39±1.55 g, p=0.009). The 2 SSA-positive groups had lymphocytopenia and high serum IgG levels. The focus scores and fibrosis of the biopsy specimens did not differ significantly. Two ACA+SSA+ patients had pulmonary arterial hypertension. Other extraglandular involvement including malignant lymphoma showed no significant differences in the 3 groups. Serum IL-12 was high in the ACA+SSA+ group, while IFN-γ was high in the 2 SSA-positive groups. Conclusions Clinicopathological data and serum cytokine profile in the 3 groups differed. Although the 2 ACA-positive groups had some features of systemic sclerosis such as Raynaud9s phenomenon, not many patients showed sclerodactyly at diagnosis and no patient developed new skin sclerosis during the follow-up. The ACA+SSA+ group may be more likely to have features of SS than those of systemic sclerosis because they showed a lower salivary flow rate in Saxon9s test than that in the ACA-SSA+ SS which was typical SS. Serum IL-12 was high in the ACA+SSA+ group, and there are reports that IL-12 transgenic mice mimic human Sjogren9s syndrome [3]. Thus, measuring ACA is an important component in the management of SS. References J Rheumatol 2001;28:2238-44. J Autoimmun 2012;39:15-26. Arthritis Rheum 2009;60:3633-41. Acknowledgements We thank John Gelblum for his critical reading of the manuscript. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3149

Masayasu Kitano - One of the best experts on this subject based on the ideXlab platform.

  • thu0190 ultrasonagraphic assessment of submandibular glands in anti Centromere Antibody positive and negative primary sjogren s syndrome patients
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, S. Uchiyama, Masayasu Kitano, T. Iwasaki, Hajime Sano, T. Hashimoto
    Abstract:

    Background Primary Sjogren’s Syndrome (pSS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration into exocrine glands. Previous reports have demonstrated that a subgroup of anti-Centromere Antibody (ACA) positive pSS (ACA+/pSS) represents intermediate features between ACA negative pSS (ACA-/pSS) and limited cutaneous systemic sclerosis. ACA+/pSS patients had a higher prevalence of Raynoud’s phenomenon, primary biliary cirrhosis (PBC) and fibrotic change of minor salivary glands compared to ACA-/pSS patients. Objectives We previously reported that submandibular gland (SG) ultrasonagraphy (US) is a useful noninvasive and inexpensive procedure for the evaluation of the morphological changes of salivary gland involvement in pSS patients (International Symposium on Sjogren’s Syndrome 2002, EULAR 2009). In the present study, we evaluated SG by using US in ACA+/pSS and ACA-/pSS patients. Methods Twenty ACA+/pSS and 30 ACA-/pSS patients were studied. SG involvement was evaluated by a single blinded observer using US staging (range 1 to 4) that assigns points to the glandular size, different degree of glandular inhomogeneity and contrast of SG to diagastric muscle. The pulsatility index (PI) and resistance index (RI) were calculated by the pulsed wave traces by power Doppler US at the internal SG facial arteries. All pSS patients were evaluated for the presence of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, Raynoud’s phenomenon, cutaneous manifestation, PBC and joint involvement. We also analyzed ACA, anti-SS-A antibodies, anti-SS-B antibodies, anti-M2 antibodies, rheumatoid factor (RF) and γ-globulin in serum from pSS patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 Antibody and histopathological findings. Results ACA+/pSS and ACA-/pSS subgroup did not differ in median age and the amount of whole saliva by gum test. The immunological parameters (anti-SS-A antibodies, anti-SS-B antibodies, RF and hyper γ-globulinemia) showed no significant differences between these subgroups. The prevalences of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, cutaneous manifestation and joint involvement showed no differences between theses subgroups. However, the prevalence of PBC was significantly higher in ACA+/pSS patients than in ACA-/pSS patients (25.0% vs 3.3%, p=0.02). The prevalence of Raynoud’s phenomenon was tended to be higher in ACA+/pSS patients compared to ACA-/pSS patients (p=0.06). The US staging score was not significantly different between these subgroups (ACA+pSS; 2.45±1.1 vs ACA-pSS; 1.97±1.1), although the size of SG was significantly smaller in ACA+pSS than in ACA-pSS patients (203.0±76.0 vs 261.2±94.0 mm 2 , p Conclusions By using US, we observed a higher prevalence of SG atrophy and low blood flow in ACA+/pSS patients as compared to ACA-/pSS patients. US assessment may be useful to evaluate the differences of histopathological changes of salivary glands between ACA+/pSS and ACA-/pSS patients. Disclosure of Interest None Declared

  • THU0190 Ultrasonagraphic assessment of submandibular glands in anti-Centromere Antibody positive and negative primary sjogren’s syndrome patients
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, S. Uchiyama, Masayasu Kitano, T. Iwasaki, Hajime Sano, T. Hashimoto
    Abstract:

    Background Primary Sjogren’s Syndrome (pSS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration into exocrine glands. Previous reports have demonstrated that a subgroup of anti-Centromere Antibody (ACA) positive pSS (ACA+/pSS) represents intermediate features between ACA negative pSS (ACA-/pSS) and limited cutaneous systemic sclerosis. ACA+/pSS patients had a higher prevalence of Raynoud’s phenomenon, primary biliary cirrhosis (PBC) and fibrotic change of minor salivary glands compared to ACA-/pSS patients. Objectives We previously reported that submandibular gland (SG) ultrasonagraphy (US) is a useful noninvasive and inexpensive procedure for the evaluation of the morphological changes of salivary gland involvement in pSS patients (International Symposium on Sjogren’s Syndrome 2002, EULAR 2009). In the present study, we evaluated SG by using US in ACA+/pSS and ACA-/pSS patients. Methods Twenty ACA+/pSS and 30 ACA-/pSS patients were studied. SG involvement was evaluated by a single blinded observer using US staging (range 1 to 4) that assigns points to the glandular size, different degree of glandular inhomogeneity and contrast of SG to diagastric muscle. The pulsatility index (PI) and resistance index (RI) were calculated by the pulsed wave traces by power Doppler US at the internal SG facial arteries. All pSS patients were evaluated for the presence of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, Raynoud’s phenomenon, cutaneous manifestation, PBC and joint involvement. We also analyzed ACA, anti-SS-A antibodies, anti-SS-B antibodies, anti-M2 antibodies, rheumatoid factor (RF) and γ-globulin in serum from pSS patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 Antibody and histopathological findings. Results ACA+/pSS and ACA-/pSS subgroup did not differ in median age and the amount of whole saliva by gum test. The immunological parameters (anti-SS-A antibodies, anti-SS-B antibodies, RF and hyper γ-globulinemia) showed no significant differences between these subgroups. The prevalences of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, cutaneous manifestation and joint involvement showed no differences between theses subgroups. However, the prevalence of PBC was significantly higher in ACA+/pSS patients than in ACA-/pSS patients (25.0% vs 3.3%, p=0.02). The prevalence of Raynoud’s phenomenon was tended to be higher in ACA+/pSS patients compared to ACA-/pSS patients (p=0.06). The US staging score was not significantly different between these subgroups (ACA+pSS; 2.45±1.1 vs ACA-pSS; 1.97±1.1), although the size of SG was significantly smaller in ACA+pSS than in ACA-pSS patients (203.0±76.0 vs 261.2±94.0 mm 2 , p Conclusions By using US, we observed a higher prevalence of SG atrophy and low blood flow in ACA+/pSS patients as compared to ACA-/pSS patients. US assessment may be useful to evaluate the differences of histopathological changes of salivary glands between ACA+/pSS and ACA-/pSS patients. Disclosure of Interest None Declared

  • AB0502 Long-term follow-up of esophageal diameter in patients with anti-Centromere Antibody sero-positive systemic sclerosis and primary sjögren’s syndrome
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, Masayasu Kitano, T. Iwasaki, Hajime Sano, H. Kuno, T. Hashimoto
    Abstract:

    Background Anti-Centromere antibodies (ACA) are characteristic autoantibodies which are detected in patients with systemic sclerosis (SSc) and primary Sjogren’s syndrome (pSS). We previously reported that ACA are a useful marker of esophageal dilatation in patients with SSc (EULAR2010). Objectives The aim of this study was to examine the role of ACA for esophageal dysfunction in patients with SSc and pSS using the barium esophagogram during long-term follow up. Methods Twelve ACA sero-positive pSS (ACA+/pSS) and 20 ACA sero-positive SSc (ACA+/SSc) patients were studied. Barium esophagogram was performed in all ACA+/pSS and ACA+/SSc patients by receiving 4 successive swallows of 20 ml of barium at 30 sec intervals in the standing position. The esophageal dilatation was examined by measurement of maximal diameters at lower esophagus by a single blinded observer. All ACA+/pSS and ACA+/SSc patients were evaluated for the presence of cutaneous subtype, interstitial pneumonia, joint involvement, chronic thyroiditis, primary biliary cirrhosis (PBC) and Raynoud’s phenomenon. We also analyzed γ-globulin, rheumatoid factor (RF), anti-SS-A antibodies, anti-SS-B antibodies, anti-Topoisomerase I antibodies (Topo-I) and anti-U1 RNP antibodies in serum from all patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 antibodies and histopathological findings. Results All ACA+/pSS and ACA+/SSc patients were women. Follow-up period (6.88±1.98 vs 7.14±1.63 years) and median age (64.8±11.2 vs 59.5±10.6 years) were not different between ACA+/pSS and ACA+/SSc patients. There was no significant difference between ACA+/pSS and ACA+/SSc patients in the prevalence of interstitial pneumonia, joint involvement, chronic thyroiditis, PBC, hyper γ-globulinemia and positivity of RF. However, the prevalence of anti-SS-A Antibody and anti-SS-B Antibody sero-positive patients were significantly higher in ACA+/pSS than in ACA+/SSc (66.7% vs 20.0%, p=0.008, 25.0 vs 0.0%, p=0.019). Anti-Topo-I antibodies and anti-U1 RNP antibodies were not detected in all patients. Although the esophageal diameters were not significantly different between these groups at the initial evaluation (22.1±2.5mm vs 26.6±8.4mm), they were significantly wider in ACA+/SSc patients than in ACA+/pSS patients at the end of follow-up (21.1±4.1mm vs 30.8±10.5mm, p=0.005). In addition, ACA+/SSc patients showed significant increase of the percentage change of esophageal diameters during follow-up when compared with ACA+/pSS patients (95.3% vs 119.5%, p=0.047). Conclusions The present study demonstrated that esophageal dilatation was progressive in ACA sero-positive patients during long-term follow-up. However, the severity of esophageal dilatation depended on the underlying diseases. Another factor other than ACA seems to contribute to esophageal dysfunction. Disclosure of Interest None Declared

Hajime Sano - One of the best experts on this subject based on the ideXlab platform.

  • thu0190 ultrasonagraphic assessment of submandibular glands in anti Centromere Antibody positive and negative primary sjogren s syndrome patients
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, S. Uchiyama, Masayasu Kitano, T. Iwasaki, Hajime Sano, T. Hashimoto
    Abstract:

    Background Primary Sjogren’s Syndrome (pSS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration into exocrine glands. Previous reports have demonstrated that a subgroup of anti-Centromere Antibody (ACA) positive pSS (ACA+/pSS) represents intermediate features between ACA negative pSS (ACA-/pSS) and limited cutaneous systemic sclerosis. ACA+/pSS patients had a higher prevalence of Raynoud’s phenomenon, primary biliary cirrhosis (PBC) and fibrotic change of minor salivary glands compared to ACA-/pSS patients. Objectives We previously reported that submandibular gland (SG) ultrasonagraphy (US) is a useful noninvasive and inexpensive procedure for the evaluation of the morphological changes of salivary gland involvement in pSS patients (International Symposium on Sjogren’s Syndrome 2002, EULAR 2009). In the present study, we evaluated SG by using US in ACA+/pSS and ACA-/pSS patients. Methods Twenty ACA+/pSS and 30 ACA-/pSS patients were studied. SG involvement was evaluated by a single blinded observer using US staging (range 1 to 4) that assigns points to the glandular size, different degree of glandular inhomogeneity and contrast of SG to diagastric muscle. The pulsatility index (PI) and resistance index (RI) were calculated by the pulsed wave traces by power Doppler US at the internal SG facial arteries. All pSS patients were evaluated for the presence of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, Raynoud’s phenomenon, cutaneous manifestation, PBC and joint involvement. We also analyzed ACA, anti-SS-A antibodies, anti-SS-B antibodies, anti-M2 antibodies, rheumatoid factor (RF) and γ-globulin in serum from pSS patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 Antibody and histopathological findings. Results ACA+/pSS and ACA-/pSS subgroup did not differ in median age and the amount of whole saliva by gum test. The immunological parameters (anti-SS-A antibodies, anti-SS-B antibodies, RF and hyper γ-globulinemia) showed no significant differences between these subgroups. The prevalences of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, cutaneous manifestation and joint involvement showed no differences between theses subgroups. However, the prevalence of PBC was significantly higher in ACA+/pSS patients than in ACA-/pSS patients (25.0% vs 3.3%, p=0.02). The prevalence of Raynoud’s phenomenon was tended to be higher in ACA+/pSS patients compared to ACA-/pSS patients (p=0.06). The US staging score was not significantly different between these subgroups (ACA+pSS; 2.45±1.1 vs ACA-pSS; 1.97±1.1), although the size of SG was significantly smaller in ACA+pSS than in ACA-pSS patients (203.0±76.0 vs 261.2±94.0 mm 2 , p Conclusions By using US, we observed a higher prevalence of SG atrophy and low blood flow in ACA+/pSS patients as compared to ACA-/pSS patients. US assessment may be useful to evaluate the differences of histopathological changes of salivary glands between ACA+/pSS and ACA-/pSS patients. Disclosure of Interest None Declared

  • THU0190 Ultrasonagraphic assessment of submandibular glands in anti-Centromere Antibody positive and negative primary sjogren’s syndrome patients
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, S. Uchiyama, Masayasu Kitano, T. Iwasaki, Hajime Sano, T. Hashimoto
    Abstract:

    Background Primary Sjogren’s Syndrome (pSS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration into exocrine glands. Previous reports have demonstrated that a subgroup of anti-Centromere Antibody (ACA) positive pSS (ACA+/pSS) represents intermediate features between ACA negative pSS (ACA-/pSS) and limited cutaneous systemic sclerosis. ACA+/pSS patients had a higher prevalence of Raynoud’s phenomenon, primary biliary cirrhosis (PBC) and fibrotic change of minor salivary glands compared to ACA-/pSS patients. Objectives We previously reported that submandibular gland (SG) ultrasonagraphy (US) is a useful noninvasive and inexpensive procedure for the evaluation of the morphological changes of salivary gland involvement in pSS patients (International Symposium on Sjogren’s Syndrome 2002, EULAR 2009). In the present study, we evaluated SG by using US in ACA+/pSS and ACA-/pSS patients. Methods Twenty ACA+/pSS and 30 ACA-/pSS patients were studied. SG involvement was evaluated by a single blinded observer using US staging (range 1 to 4) that assigns points to the glandular size, different degree of glandular inhomogeneity and contrast of SG to diagastric muscle. The pulsatility index (PI) and resistance index (RI) were calculated by the pulsed wave traces by power Doppler US at the internal SG facial arteries. All pSS patients were evaluated for the presence of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, Raynoud’s phenomenon, cutaneous manifestation, PBC and joint involvement. We also analyzed ACA, anti-SS-A antibodies, anti-SS-B antibodies, anti-M2 antibodies, rheumatoid factor (RF) and γ-globulin in serum from pSS patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 Antibody and histopathological findings. Results ACA+/pSS and ACA-/pSS subgroup did not differ in median age and the amount of whole saliva by gum test. The immunological parameters (anti-SS-A antibodies, anti-SS-B antibodies, RF and hyper γ-globulinemia) showed no significant differences between these subgroups. The prevalences of chronic thyroiditis, interstitial pneumonia, interstitial nephritis, cutaneous manifestation and joint involvement showed no differences between theses subgroups. However, the prevalence of PBC was significantly higher in ACA+/pSS patients than in ACA-/pSS patients (25.0% vs 3.3%, p=0.02). The prevalence of Raynoud’s phenomenon was tended to be higher in ACA+/pSS patients compared to ACA-/pSS patients (p=0.06). The US staging score was not significantly different between these subgroups (ACA+pSS; 2.45±1.1 vs ACA-pSS; 1.97±1.1), although the size of SG was significantly smaller in ACA+pSS than in ACA-pSS patients (203.0±76.0 vs 261.2±94.0 mm 2 , p Conclusions By using US, we observed a higher prevalence of SG atrophy and low blood flow in ACA+/pSS patients as compared to ACA-/pSS patients. US assessment may be useful to evaluate the differences of histopathological changes of salivary glands between ACA+/pSS and ACA-/pSS patients. Disclosure of Interest None Declared

  • AB0502 Long-term follow-up of esophageal diameter in patients with anti-Centromere Antibody sero-positive systemic sclerosis and primary sjögren’s syndrome
    Annals of the Rheumatic Diseases, 2013
    Co-Authors: Naoaki Hashimoto, Masayasu Kitano, T. Iwasaki, Hajime Sano, H. Kuno, T. Hashimoto
    Abstract:

    Background Anti-Centromere antibodies (ACA) are characteristic autoantibodies which are detected in patients with systemic sclerosis (SSc) and primary Sjogren’s syndrome (pSS). We previously reported that ACA are a useful marker of esophageal dilatation in patients with SSc (EULAR2010). Objectives The aim of this study was to examine the role of ACA for esophageal dysfunction in patients with SSc and pSS using the barium esophagogram during long-term follow up. Methods Twelve ACA sero-positive pSS (ACA+/pSS) and 20 ACA sero-positive SSc (ACA+/SSc) patients were studied. Barium esophagogram was performed in all ACA+/pSS and ACA+/SSc patients by receiving 4 successive swallows of 20 ml of barium at 30 sec intervals in the standing position. The esophageal dilatation was examined by measurement of maximal diameters at lower esophagus by a single blinded observer. All ACA+/pSS and ACA+/SSc patients were evaluated for the presence of cutaneous subtype, interstitial pneumonia, joint involvement, chronic thyroiditis, primary biliary cirrhosis (PBC) and Raynoud’s phenomenon. We also analyzed γ-globulin, rheumatoid factor (RF), anti-SS-A antibodies, anti-SS-B antibodies, anti-Topoisomerase I antibodies (Topo-I) and anti-U1 RNP antibodies in serum from all patients. The diagnosis of PBC was based on liver function test, the presence of serum anti-M2 antibodies and histopathological findings. Results All ACA+/pSS and ACA+/SSc patients were women. Follow-up period (6.88±1.98 vs 7.14±1.63 years) and median age (64.8±11.2 vs 59.5±10.6 years) were not different between ACA+/pSS and ACA+/SSc patients. There was no significant difference between ACA+/pSS and ACA+/SSc patients in the prevalence of interstitial pneumonia, joint involvement, chronic thyroiditis, PBC, hyper γ-globulinemia and positivity of RF. However, the prevalence of anti-SS-A Antibody and anti-SS-B Antibody sero-positive patients were significantly higher in ACA+/pSS than in ACA+/SSc (66.7% vs 20.0%, p=0.008, 25.0 vs 0.0%, p=0.019). Anti-Topo-I antibodies and anti-U1 RNP antibodies were not detected in all patients. Although the esophageal diameters were not significantly different between these groups at the initial evaluation (22.1±2.5mm vs 26.6±8.4mm), they were significantly wider in ACA+/SSc patients than in ACA+/pSS patients at the end of follow-up (21.1±4.1mm vs 30.8±10.5mm, p=0.005). In addition, ACA+/SSc patients showed significant increase of the percentage change of esophageal diameters during follow-up when compared with ACA+/pSS patients (95.3% vs 119.5%, p=0.047). Conclusions The present study demonstrated that esophageal dilatation was progressive in ACA sero-positive patients during long-term follow-up. However, the severity of esophageal dilatation depended on the underlying diseases. Another factor other than ACA seems to contribute to esophageal dysfunction. Disclosure of Interest None Declared