HLA-BW35 AND B5 IN JAPANESE PATIENTS WITH GRAVES' DISEASE

1977 ◽  
Vol 86 (4) ◽  
pp. 754-757 ◽  
Author(s):  
A. Kawa ◽  
S. Nakamura ◽  
M. Nakazawa ◽  
S. Sakaguchi ◽  
T. Kawabata ◽  
...  

ABSTRACT Thirty-three Japanese patients with Graves' disease and 106 healthy controls living in the Kagoshima area, the southernmost part of the Japanese mainland, were HLA typed by the NIH method. None of them were related to each other. The only antigen showing an increased frequency in Japanese patients with Graves' disease was HLA-BW35 (corrected P < 0.02). A decreased frequency of B5 in the patients was also statistically significant (corrected P < 0.02).

1989 ◽  
Vol 30 (5) ◽  
pp. 525-530 ◽  
Author(s):  
HAJIME TAMAI ◽  
YUKIHIKO TAKAICHI ◽  
TETSUYA MORITA ◽  
GEN KOMAKI ◽  
SUNAO MATSUBAYASHI ◽  
...  

Thyroid ◽  
2000 ◽  
Vol 10 (6) ◽  
pp. 475-480 ◽  
Author(s):  
Yoshiyuki Ban ◽  
Yoshio Ban ◽  
Matsuo Taniyama ◽  
Takashi Katagiri

2001 ◽  
pp. 119-127 ◽  
Author(s):  
A Thrasyvoulides ◽  
M Sakarellos-Daitsiotis ◽  
G Philippou ◽  
A Souvatzoglou ◽  
C Sakarellos ◽  
...  

OBJECTIVE: Thyroglobulin (Tg) is a large autoantigen involved in autoimmune thyroid diseases. Tg epitopes have, so far, been identified within large peptides. In the present study, we used small synthetic peptides to finely map serological epitopes on the highly immunogenic C-terminal region of Tg. Homology of this region to acetylcholinesterase (AChE) has been implicated in the pathogenesis of thyroid eye disease (TED) through cross-reactive antibodies. METHODS: We tested total IgG purified from four pilot Graves' disease (GD) sera reactive with both Tg and AChE and from three healthy controls, for reactivity against overlapping 20mer peptides (pin synthesis) covering the sequence 2171-2748 of human Tg. Antibody-reactive peptides were subsequently synthesized by a solid-phase technique for confirmation with a large number of sera: 99 GD, 32 Hashimoto's thyroiditis (HT) and 45 healthy controls. RESULTS: Peptides TgP15, TgP26 and TgP41 (amino acids 2339-2358, 2471-2490 and 2651-2670 respectively) were found to be targets of autoantibodies on intact Tg, recognized by a statistically significant proportion of GD sera (22.2%, 35.4% and 30.3% respectively), compared with HT (0%, 15.6% and 6.3% respectively) and healthy controls (0%, 4.4% and 4.4% respectively). The majority of GD sera (56.6%) were positive for at least one of the three peptides. In GD, TgP26 reactivity was found to be associated with TED (48.6% with TED versus 25.5% without TED, P<0.05). CONCLUSION: Some epitopes on the C-terminal region of Tg are associated with GD. A subset of Tg-reactive autoantibodies, directed to this region, is associated with TED and may be involved in the development of the disease.


Cornea ◽  
2000 ◽  
Vol 19 (Supplement 2) ◽  
pp. S130
Author(s):  
Yoshitsugu Tagawa ◽  
Rieko Kishimoto ◽  
Yasufumi Amino ◽  
Kazuyuki Yamamoto ◽  
Takafumi Nakano ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Jing Qin ◽  
Jin Zhou ◽  
Chenling Fan ◽  
Na Zhao ◽  
Yongping Liu ◽  
...  

Th17 and regulatory lymphocyte subsets such as Tregs and Bregs have been reported to play important roles in autoimmune diseases. The aim of this work was to perform quantitative studies of circulating Th17, Tregs, and Bregs in patients with new-onset Graves’ disease (GD). Twenty GD patients and 20 healthy controls were involved in this study. Blood samples were taken for flow cytometry detection of CD4+IL-17+ Th17, CD4+Foxp3+ Tregs, and CD19+CD1dhiCD5+ Bregs and meanwhile, for real-time PCR measurement of gene expressions of RORγt, IL-17 and IL-10. The proportions of Tregs and Bregs as well as the Foxp3 gene expression but not IL-10 were significantly decreased in GD group compared with the healthy controls. The frequency of Th17 together with the gene expressions of RORγt and IL-17 were significantly increased in the GD group. Furthermore, the Th17/Treg ratio was also significantly higher in GD group. A significant positive correlation between Th17 and TSAb (r=0.656, p<0.001) but significant negative correlations between Treg/Breg and TSAb (r=-0.339, p=0.032; r=-0.759, p<0.001) were identified among the participants. This study indicated that increased Th17 and impaired Treg responses, along with a decreased number of CD19+CD1dhiCD5+ Breg cells, were involved in GD pathogenesis.


2011 ◽  
Vol 96 (11) ◽  
pp. E1866-E1870 ◽  
Author(s):  
Lingyan Xu ◽  
Xinran Ma ◽  
Yanyan Wang ◽  
Xiaoli Li ◽  
Yicheng Qi ◽  
...  

Abstract Context: Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. Its pathogenesis is tightly involved with aberrant proinflammatory cytokine production. Osteopontin (OPN), an extracellular matrix protein of pleiotropic properties, has recently been recognized as a potent inflammatory cytokine in several autoimmune diseases. Objective: This study sought to explore the pathophysiological role of OPN in GD by comparing OPN levels in initial GD patients and healthy controls. Methods: Seventy-six patients who met criteria for initial GD and sixty-five healthy controls were recruited. OPN and other clinical GD diagnosis parameters were measured. In addition, the coexpression of several OPN receptors as well as various nuclear factor-κB (NF-κB) downstream target genes were examined in peripheral blood mononuclear cells from human subjects. The effect of OPN on NF-κB activation was determined by in vitro assays. Results: We demonstrated for the first time that the OPN levels are enhanced in serum from GD patients. OPN levels are strongly associated with clinical serum parameters for GD diagnosis. The coexpression of selective OPN receptors and inflammatory response genes was enhanced in peripheral blood mononuclear cells from GD patients. Furthermore, serum from GD patients activated NF-κB activity in vitro, which was significantly suppressed by OPN monoclonal antibody abrogation. Conclusion: These data indicated a clinical correlation between serum OPN levels and GD. OPN could affect GD development through NF-κB activation and the subsequent changes in inflammatory milieu. OPN could serve as a novel biomarker for GD as well as a potential target for GD treatment.


2009 ◽  
Vol 161 (5) ◽  
pp. 787-793 ◽  
Author(s):  
Jacek Daroszewski ◽  
Edyta Pawlak ◽  
Lidia Karabon ◽  
Irena Frydecka ◽  
Anna Jonkisz ◽  
...  

ObjectiveGraves' disease (GD) is an autoimmune disorder with genetic and environmental background. CTLA-4 is a candidate gene for thyroid autoimmunity. Increased serum levels of soluble CTLA-4 (sCTLA-4) were found in some autoimmune diseases.AimThe aim of the study was to evaluate the relation between sCTLA-4 level and clinical manifestation of Graves' ophthalmopathy (GO), thyroid status, and CTLA-4 gene polymorphisms.DesignSerum sCTLA-4 concentrations were determined in 93 GO patients and 93 healthy controls. In the GO group, CTLA-4 gene was genotyped in five polymorphic sites: g.319C>T, c.49A>G, CT60 by means of PRC-RFLP, Jo31, and g.*642AT(8_33) by means of minisequencing assay.ResultsSerum sCTLA-4 level was significantly higher in the GO group than in controls (median: 7.94 vs 0.00 ng/ml, P=0.000001). This level was higher in severe than in nonsevere GO (median: 10.3 vs 5.6 ng/ml, P=0.01). sCTLA-4 concentration was related neither to the activity of GO nor to thyroid function. Elevated sCTLA-4 levels were observed in carriers Jo31[G] allele (genotype GG+GT) as compared with subjects with an absence of the [G] allele (TT genotype; median: 9.18 vs 4.0 ng/ml, P=0.02). Also patients possessing CT60[G] allele (genotype GG+GA) had higher serum sCTLA-4 levels than subjects who lack the [G] allele (AA genotype; median: 8.73 vs 2.28 ng/ml, P=0.03).ConclusionsIt was shown for the first time that increased serum concentration of sCTLA-4 correlate with the severity of GO. Genetic variation in the CTLA-4 gene region in GD patients at least partially determines the level of sCTLA-4.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Lina Geng ◽  
Jun Yang ◽  
Xinyi Tang ◽  
Huiyong Peng ◽  
Jie Tian ◽  
...  

Signaling lymphocytic activation molecule (SLAM) and SLAM-associated protein (SAP) play important role in inflammatory and autoimmune diseases. Our study is aimed at detecting the expression of SLAM and SAP in patients with Graves’ disease (GD) and analyzing the effect of SLAM/SAP on circulating blood CD4+CXCR5+Foxp3+ follicular regulatory T (Tfr) cells. The level of SAP in CD4+CXCR5+ T cells and the level of SLAM on CD19+ B cells were significantly increased in the patients with GD, but no significant difference in the level of SLAM on CD4+CXCR5+ T cells was observed between the patients with GD and the healthy controls. A decrease in the percentage of Foxp3+ cells in CD4+CXCR5+ T cells was observed following anti-SLAM treatment, but the percentages of IFN-γ+ cells, IL-4+ cells, and IL-17+ cells showed no obvious differences. The proportion of circulating Tfr cells was decreased in the patients with GD, and the proportion of circulating Tfr cells had a negative correlation with the level of SAP in CD4+CXCR5+ T cells and the levels of autoantibodies in the serum of the patients with GD. Our results suggested that the SLAM/SAP signaling pathway is involved in the decrease of circulating Tfr cells in Graves’ disease.


2021 ◽  
Author(s):  
Lina Geng ◽  
Jun Yang ◽  
Xinyi Tang ◽  
Huiyong Peng ◽  
Jie Tian ◽  
...  

Abstract Background: Signaling lymphocytic activation molecule (SLAM) and SLAM-associated protein (SAP) play important role in inflammatory and autoimmune diseases. Our study aimed to detect the expression of SLAM and SAP in patients with Graves’ disease (GD) and analyze the effect of SLAM/SAP on circulating blood CD4+CXCR5+ Foxp3+ follicular regulatory T (Tfr) cells.Methods: The expression of SLAM and SAP was assessed by flow cytometry and real-time PCR. The percentages of IFN-γ+ cells, IL-4+ cells, IL-17+ cells and Foxp3+ cells in CD4+CXCR5+ T cells and circulating CD4+CXCR5+ Foxp3+ Tfr cells after treatment with anti-SLAM and anti-CD3 antibodies were also assessed by flow cytometry. The correlations between the percentages of Tfr cells and the levels of autoantibodies as well as SAP were analyzed.Results: The level of SAP in CD4+CXCR5+ T cells and the level of SLAM on CD19+ B cells were significantly increased in the patients with GD, but no significant difference in the level of SLAM on CD4+CXCR5+ T cells was observed between the patients with GD and the healthy controls. A decrease in the percentage of Foxp3+ cells in CD4+CXCR5+ T cells was observed following anti-SLAM treatment, but the percentages of IFN-γ+ cells, IL-4+ cells and IL-17+ cells showed no obvious differences. The proportion of circulating Tfr cells was decreased in the patients with GD, and the proportion of circulating Tfr cells had a negative correlation with the level of SAP in CD4+CXCR5+ T cells and the levels of autoantibodies in the serum of the patients with GD.Conclusions: Our results indicate that the SLAM/SAP signaling pathway regulates Tfr cells, which may be involved in the pathogenesis of Graves’ disease.


1994 ◽  
Vol 41 (6) ◽  
pp. 599-603 ◽  
Author(s):  
EIYU KATSUREN ◽  
TAKUYA AWATA ◽  
CHIAKI MATSUMOTO ◽  
KUNIHIRO YAMAMOTO

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