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1. |
The Preferential Expression of the Anti-DNA Associated 8.12 Idiotype in Lupus is not Genetically Controlled |
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Autoimmunity,
Volume 18,
Issue 1,
1994,
Page 1-6
LivnehAvi,
GazitEphraim,
DiamondBetty,
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摘要:
Anti-DNA antibodies are autoantibodies unique to systemic lupus erythematosus. Studies of their structure have demonstrated cross reactive idiotypes present in genetically unrelated individuals. Despite much research, it is still not clear what triggers their production and what governs the presence of particular idiotypic determinants in their structure. To study the role of genetic and environmental factors in the expression of idiotypc, we analyzed sera of SLE patients, their family members and nonautoimmune individuals vaccinated with pneumococcal polysaccharide, for the presence of the 8.12 idiotype, which is present on lambda light chains of anti-DNA antibodies. Elevated titers of the 8.12 idiotype was found in the serum of 57% of SLE patients. Elevated titers were present in only 9% of family members, and always associated with the presence of high levels of IgG anti-DNA antibodies. Following vaccination with pneumococcal polysaccharide, 8.12 reactive anti-pncumococcal antibodies were produced by 7 of 10 non-autoimmune individuals and 8.12 reactive anti-DNA antibodies by one. These results suggest that 8.12 reactive antibodies are antigen driven and bind structurally related antigens, but there is no evidence that expression of this idiotype is genetically controlled.
ISSN:0891-6934
DOI:10.3109/08916939409014673
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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2. |
A Model to Study Viral and Cytokine Involvement in Sjogren's Syndrome |
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Autoimmunity,
Volume 18,
Issue 1,
1994,
Page 7-14
ClarkD. A.,
LameyP. J.,
JarrettR. F.,
OnionsD. E.,
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摘要:
To investigate mechanisms that may be important in the pathogenesis of Sjogren's syndrome (SS) we developed a protocol for the growth of salivary gland epithelial cells in culture. We examined the effect that viral infection has on the cellular location of the autoantigen La. Autoantibodies to La arc common in SS and it has been porposed that viral infection may result in cell membrane expression of La. Co-expression of MHC class II molecules in infected cells could lead to the presentation of La peptides to the immune system. Advcnovirus infection of salivary gland epithelial cells resulted in an altered nuclear staining of La. Treatment with interferon-y resulted in the expression of La in the cell cytoplasm and HLA-DR molecules at the cell surface. These findings suggest that a cytokine-driven mechanism may generate an autoimmune response to La in SS. Using the polymerase chain reaction (PCR) we tested salivary gland epithelial cell cultures for the presence of human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). Only HHV-6 was detected in 2 of 10 salivary gland epithelial cell cultures although the presence of HHV-6 was not associated with SS. Primary salivary gland cultures may prove useful as anin vitromodel to study mechanisms of autoimmunity in SS.
ISSN:0891-6934
DOI:10.3109/08916939409014674
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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3. |
Loss of Rt6 Message and Most Circulating T Cells after Thymectomy of Diabetes Prone BB Rats |
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Autoimmunity,
Volume 18,
Issue 1,
1994,
Page 15-22
SarkarProbir,
CrisáLaura,
McKeeverUna,
BortellRita,
HandlerEugene,
MordesJohn P.,
WaiteDebra,
SchoenbaumAmy,
HaagFriedrich,
NolteFriedrich Koch,
Gunther ThieleHeinz,
GreinerDale L.,
RossiniAldo A.,
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摘要:
T cells expressing the RT6 surface alloantigcn perform important immunoregulatory functions in the rat. Diabetes prone (DP) BB rats arc deficient in circulating RT6+T cells and develop spontaneous autoimmune diabetes mellitus. Transfusions leading to cngraftment of RT6′T cells prevent the disease. Coisogcnic diabetes resistant (DR) BB rats do circulate RT6^ T cells and are free of disease. We investigated the basis for the deficiency of RT6 * T cells in the DP-BB rat and made the following observations. 1. Thymectomy causes the rapid loss of most peripheral T cells in the DP-BB rat. 2. Concomitant with the loss of T cells is the total loss of mRNA encoding RT6. 3. In contrast to the effects observed in peripheral lymphoid tissues, thymectomy does not lead to a detectable loss in RT6+protein found in the small intestine. We conclude that the deficiency of RT6+peripheral T cells in the DP-BB rat is due either to their short life span or to their reduced proliferative capacity following release from the thymus.
ISSN:0891-6934
DOI:10.3109/08916939409014675
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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4. |
Effect of Cepharanthin and Cytochalasin D On Platelet Internalization of Anti-Glycoprotein IIb/IIIa Antibodies |
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Autoimmunity,
Volume 18,
Issue 1,
1994,
Page 23-29
NomuraShosaku,
YanabuMutsumasa,
MiyakeTetsuya,
MiyazakiYasuhiko,
KawakatsuToshihiro,
KidoHirofumi,
YamaguchiKazuyuki,
FukuroiTsutomu,
KagawaHideo,
SuzukiMasahiko,
KokawaTerutoshi,
FukuharaShirou,
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摘要:
The effects of ccpharanthin and cytochalasin D on the internalization of anti-glycoprotein Ilb/llla antibodies by platelets were investigated in 13 patients with chronic immune thrombocytopenic purpura who had circulating anti-glycoprotcin Ilb/IIIa autoantibodies. Unfixed platelets were incubated with a monoclonal anti-glycoprotcin Ilb/IIIa antibody (NNKY1-32) or with platelet-binding IgG from the patients (which contained anti-glycoprotein Ilb/IIIa antibodies). Flow cytometry showed that the binding of NNKY 1-32 to platelets was markedly decreased after incubation for 120 min compared with incubation for 10 min. This decrease was inhibited by ccpharanthin but not by cytochalasin D. Platelet-binding IgG also showed markedly reduced binding after incubation for 120 min compared with 10 min, and this decrease was inhibited by both ccpharanthin and cytochalasin D. Cytochalasin D inhibits platelet cytoskcletal activity while cepharanthin does not. Therefore, our results suggest that the internalization of anti-glycoprotcin Ilb/IIIa antibodies from the plasma of patients with immune thrombocytopenic purpura is related to platelet cytoskeletal reorganization, while the cytoskelton did not participate in internalization of the monoclonal anti-glycoprotcin Ilb/IIIa antibody (NNKY1-32). Cepharanthin may be useful for studying the internalization and cycling of glycoprotein Ilb/IIIa in human platelets, and it may also be potentially useful for the treatment of immune thrombocytopenic purpura.
ISSN:0891-6934
DOI:10.3109/08916939409014676
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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5. |
Iodide Induced Lymphocytic Thyroiditis in the Bb/W Rat: Evidence of Direct Toxic Effects of Iodide on Thyroid Subcellular Structure |
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Autoimmunity,
Volume 18,
Issue 1,
1994,
Page 31-40
LiMu,
BoyagesSteven C.,
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摘要:
A high dietary iodine intake accelerates the development of lymphocytic thyroiditis (LT) in the BB/W rat. Our previous studies have defined the temporal sequence of the immunolgical events triggered by excess iodide intake in these animals. It was still not clear, however, whether these observed immunological changes were a direct effect on immune effector cells, or whether they represented a secondary response to a toxic effect of iodine on thyroid tissue. In the present study, the effect of excessive iodine intake on the subcellular structure of the BB/W rat thyroid gland, particulary, whether iodide had a toxic effect independent of its immune response has been examined. BB/W rats were exosed, prenatahy through maternal drinking water, to excessive iodide at two doses (Moderate 3×10-6M iodide/1; High 3×10-3M iodide/l); a third group of BB/W rats was given tap water; till 12 weeks postnatal age. Two groups of Wistar rats received high dose iodide water or tap water for the same period of time and served as controls. Thyroid gland ultrastructure was determined by electron microscopic (EM) examination. Thyroid125I uptake and perchlorate discharge tests were also performed in separate experiments.We found that thyroid glands of non-iodine supplemented Wistar rats were morphlogically normal under EM. There were no overt changes in the iodide treated Wistar rats. By contrast, iodide treated BB/W rats exhibited marked accumulation of secondary lysosomes and lipid droplets; markedly swollen and disrupted mitochondria and extreme dilatation of rough endoplasmic reticulum (RER). These cytoplasmic changes were accompanied by nuclear changes indicative of cell necrosis, particularly in more severely affected areas. The observed changes induced by iodide were dose dependent. Only minor subcellular changes, comprising slight dilatation of the RER and mitochondrial swelling were observed in non-iodine treated BB/W rats. The morphologic changes in the iodine treated BB/W rats were associated with defects in iodine uptake and organification.These data indicate that iodide appears to have a direct toxic effect on the thyroid epithelial cell of the LT-prone BB/W rat. The pattern of tissue damage implicates involvement of oxidative stress. We speculate that iodine accelerates LT by damaging subcellular structures of thyrocytes, resulting in the formation and release of yet unknown factors which in turn attract antigen presenting cells to accelerate the immunological process.
ISSN:0891-6934
DOI:10.3109/08916939409014677
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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6. |
Epitopes on Thyroglobulin: A Study of Patients with Thyroid Disease |
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Autoimmunity,
Volume 18,
Issue 1,
1994,
Page 41-49
CaturegliPatrizio,
MariottiStefano,
KuppersRudolf C.,
BurekC. Lynne,
PincheraAldo,
RoseNoel R.,
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摘要:
Thyroglobulin antibodies (TgAbs) are typically found in autoimmune thyroid diseases and, more rarely, in nonautoimmunc thyroid diseases and healthy subjects. To determine whether TgAbs associated with different conditions recognize different epitopes on the thyroglobulin molecule, we studied 28 patients with Hashimoto's thyroiditis, 30 with Graves' disease, 21 with thyroid carcinoma, 18 with nontoxic goiter, and 25 healthy subjects. All patients were selected for the presence of TgAbs; 4/25 healthy subjects also had TgAbs. The sera were assayed for the their ability to inhibit the binding of monoclonal antibodies to thyroglobulin in an EL1SA assay. We found that: 1) TgAbs in Hashimoto's patients preferentially recognized three clusters of epitopes (II, III and typically VI). with no difference between the goitrous and the atrophic variants; 2) TgAbs in Graves' patients were directed toward cluster II, with no difference between the presence or the absence of ophthalmopathy; 3) TgAbs in thyroid carcinoma patients recognized the same clusters as Hashimoto's patients; 4) TgAbs in nontoxic goiter patients and in the four healthy subjects showed no restriction in epitope recognition. We suggest that in individuals with no overt clinical or biochemical thyroid abnormalities but with TgAbs, the finding that these TgAbs recognize particular immunodominant clusters may be utilized to predict full-blown thyroid disorders. Longitudinal studies are needed to evaluate the possible clinical application of this methodology.
ISSN:0891-6934
DOI:10.3109/08916939409014678
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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7. |
Antiphospholipid Antibodies in Patients with Idiopathic Autoimmune Haemolytic Anemia |
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Autoimmunity,
Volume 18,
Issue 1,
1994,
Page 51-56
GuzmanJaime,
CabralAntonio R.,
CabiedesJavier,
PitaLuis,
AlarconDonato,
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摘要:
Isolated cases of anti-phospholipid antibody (aPL)-associated idiopathic autoimmune haemolytic anemia (IAHA) have been recently described. To assess the significances of this association, we studied by ELISA the presence of aPL in sera from 18 patients with IAHA and 14 patients with non-autoimmune haemolysis (NON-AH). Four IAHA cases and none of the NON-AH controls showed IgM anticardiolipin antibodies (aCL) that crossreacted extensively with zwitterionic as well as with other anionic phospholipids. IgG aCL were detected in 6 patients with IAHA and in 1 patient with NON-AH; there was little cross-reactivity with other phospholipids. Our results suggest that anti-phospholipid antibodies are present in a substantial number of patients with IAHA. This humoral response does not seem to be secondary to the haemolysis proper. The potential pathogenic significance of this finding is discussed.
ISSN:0891-6934
DOI:10.3109/08916939409014679
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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8. |
Studies of IgG-Class Anticardiolipin Antibodies in Myasthenia Gravis |
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Autoimmunity,
Volume 18,
Issue 1,
1994,
Page 57-63
SanmarcoMarielle,
BernardDominique,
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摘要:
IgG-class anticardiolipin antibodies (IgG-ACA) were found in 25% of patients with myasthenia gravis. The prevalence and the level distribution were significantly different from those of a normal donor population (p<0.001). In myastcnic patients, IgG-ACA bound negatively charged, but not zwitteri-onic. phospholipids. They were significantly associated with the thymic abnormalities, thymoma and thymic hyperplasia, but not with various factors such as age, sex, antinuclear antibodies, severity of the disease and clinical thrombosis. The IgG-ACA levels did not correlate with titers of anti-acctylcholine receptor antibodies. Thus in Myasthenia Gravis, asymptomatic IgG-ACA could reflect an immune dysregulation under the influence of thymic alterations.
ISSN:0891-6934
DOI:10.3109/08916939409014680
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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9. |
The Role of VL Gene Structural Determinants in the Fine Specificity of Anti-Dna Antibodies |
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Autoimmunity,
Volume 18,
Issue 1,
1994,
Page 65-75
SinghAjay K.,
GangemiRosaria M. R.,
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摘要:
To investigate the structural contribution of the light chain of anti-DNA antibodies to fine specificity, the VKappa genes of two monoclonal anti-DNA antibodies, termed H241 and HI 02, were cloned and sequenced. HI02 and H241 are independently derived from MRL-lpr/lpr mice and differ in their line specificity: H241 binds dsDNA and normal glomeruliin vitroand deposits in the kidneyin vivowhereas HI02 binds only ssDNA and does not deposit in the kidney. Both are encoded by nearly identical VH genes but different N and D regions. Our previous results have demonstrated that the VH gene for HI02 and H241 encodes eight other anti-DNA antibodies that also differed in fine specificity. This suggested that the gene product encoded by the VH 102/241 gene, may have intrinsic affinity for DNA, but is unlikely to determine fine specificity or nephritogenicity. In the present study we examined whether the VKappa gene might account for the difference in nephritogenicity. The complete nucleotide and deduced amino acid sequence of VK 102 and VK241 revealed that they are very dissimilar to each other (<60% homology). VK 241 defined a new member of the VKappa gene family and was moderately homologous to two other VK genes encoding anti-DNA antibodies and to one VK gene encoding an anti-histone antibody all from lupus strains of mice. In addition, sequence diversity in the VK CDR1 region and position 96 of the CDR3 region was observed that may be of signficance in determining fine specificity. VK 102 was highly homologous to two other VKappa genes, VKsl7.2 and VK C8.5, both encoding anti-DNA antibodies and members of the VK20gene family. It was striking that all three members of the VK 20 gene family code for DNA reactivity. This suggests that certain VKappa genes may also be used to repeatedly code for anti-DNA reactivity.
ISSN:0891-6934
DOI:10.3109/08916939409014681
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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10. |
Analysis of the Peripheral T-Cell Receptor VP Repertoire in Newly Diagnosed Patients with Type I Diabetes |
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Autoimmunity,
Volume 18,
Issue 1,
1994,
Page 77-83
WongSusan,
WenLi,
HibberdMartin,
MillwardAnn,
DemaineAndrew,
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摘要:
Type I diabetes is an autoimmune disease characterised by a marked activation of peripheral T cells around the time of clinical diagnosis. Studies of T-cell antigen receptor Vp (TCRBV) gene usage in type I diabetes have been conflicting. Usng a semi-quantitative polymerase chain reaction technique and flow cytometry we have investigated the TCRBV gene usage of 13 newly diagnosed patients with type I diabetes and 11 normal healthy controls. No preferential TCRBV gene usage was found between patients and controls even after matching for HLA-DR3 and/or -DR4. In addition, no significant differences in TCRBV gene usage were found between sequential samples taken over a period of up to 7 months following diagnosis. These results suggest that the TCR repertoire of these patients is heterogeneous and it is unlikely that a single‘pathogenic’T-cell clone is dominant at the clinical onset of the disease.
ISSN:0891-6934
DOI:10.3109/08916939409014682
出版商:Taylor&Francis
年代:1994
数据来源: Taylor
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