Circulating immune complexes and monocyte Fc function in autoimmune diseases.

The phagocytosis of separated and adherent monocytes of patients with systemic lupus erythematosus is subnormal as compared to controls on the basis of latex and yeast uptake. The monocytes from the same patients react with antibody-coated sheep red blood cells in a significantly higher degree than normal monocytes. There is a correlation between the percentage of reactive monocytes and the serum immune complex content. After brief treatment of patients with levamisole the phagocytic function of monocytes is restored and at the same time the circulating immune complex content is decreased.     

Circulating activated T cell subsets in autoimmune thyroid diseases: differences between untreated and treated patients.

To investigate the relationships between lymphocyte subsets and thyroid function, peripheral blood lymphocytes were analysed with cell surface antigens of activated (HLA-DR+) T, helper T (CD4+ 2H4-, CD4+ 4B4+) and suppressor-inducer T (CD4+ 2H4+, CD4+ 4B4-) cells subsets in 56 patients with Graves' disease, 16 patients with Hashimoto's thyroiditis, 7 patients with typical subacute thyroiditis and 2 patients with the thyrotoxic phase of autoimmune thyroiditis. Both patients with Graves' disease and Hashimoto's thyroiditis had increased percentages of HLA-DR+ T (Ia+ CD3+) cells as well as HLA-DR+ helper-inducer T (Ia+ CD4+) cells, which seemed to be independent of treatments. The percentage of HLA-DR+ suppressor-cytotoxic T (Ia+ CD8+) cells was increased in euthyroid or hypothyroid patients with Graves' disease following treatment, but was normal in hyperthyroid patients. The percentages of Ia+ CD4+ cells and Ia+ CD8+ were also increased in patients with thyroiditis, whereas these abnormal values normalized in the remission phase. These findings suggest that an increase in Ia+ CD4+ cells characteristically occurs during immune system activation in patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis and the thyrotoxic phase of subacute thyroiditis, whereas the activated CD8+ cells in Graves' disease are induced by antithyroidal therapy.     

Association between serum markers for celiac and thyroid autoimmune diseases

Celiac disease (CD) is an autoimmune disease of the small bowel characterized by a strong genetic association with HLA - DQ2 and DQ8. Gluten is the etiological factor and the tissue enzyme transglutaminase (TGase) is its autoantigen. CD is associated with several autoimmune diseases such as type 1 diabetes, systemic lupus erythematous, rheumatoid arthritis, Sj?grens syndrome and autoimmune thyroid diseases. The aim of this study was to investigate the occurrence of serum IgA anti-endomysial and anti-human TGase antibodies in individuals with positive anti-thyroid antibody (ATA). The concordance between these two tests was also evaluated. Anti-endomysial antibodies were positive in 10 out of 456 (2.2%) and anti-human TGase were positive in 14 of 454 (3.1%) individuals with positive ATA. In control subjects they were positive in 1 of 197 (0.5%) and 2 of 198 (1%) for anti-endomysial and anti-human tissue TGase antibodies, respectively. The odds ratio (OR) for the anti-endomysial antibodies was 4.42 and for the anti-human TGase 3.12 in individuals with ATA when compared with controls. An elevated concordance index (k= 0.84) was observed between anti-endomisyal antibodies and anti-human TGase. We conclude that the determination of anti-TGase antibodies is a good test for DC screening.     

Autologous stem cell transplantation in autoimmune diseases

Since 1996, approximately 1,000 patients have received an autologous hematopoietic stem cell transplant (HSCT) as treatment for a severe autoimmune disease (AD). The European Group for Blood and Marrow Transplantation (EBMT)/European League Against Rheumatism (EULAR) Autoimmune Disease Working Party have registered more than 800 patients and works in close collaboration with networks in the United States where several hundred more AD patients have been similarly transplanted. The majority of ADs were multiple sclerosis (MS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis, and immune cytopenias. Many patients have experienced long-term disease-free remissions and immune reconstitution studies have shown in some cases that a "resetting" of autoimmunity is possible. The initially high treatment-related mortality (TRM) is reduced significantly in the later years, and the phase I/II experience is now being verified in several international prospective randomized clinical trials. In addition, the past several years have seen a growing interest in the role and potential therapeutic application of mesenchymal stem cells (MSC) in the immunomodulation of AD, as in the early experience with acute-graft-versus host disease (GvHD).     

自身免疫性甲状腺疾病患者血清纤维化指标观察

目的 观察自身免疫性甲状腺疾病(AITD)患者血清Ⅲ型前胶原(PCⅢ)和透明质酸(HA)水平.探讨其临床意义.方法 按甲状腺功能将114例AITD患者分为3组:①Graves病甲状腺功能亢进(简称甲亢)组(38例),②桥本甲状腺炎甲状腺功能低下(简称甲低)组(35例),③桥本甲状腺炎亚临床甲状腺功能低下(简称哑甲低)组(41例),另设40例健康人作为对照组.用免疫化学发光法检测以上各组人群血清游离三碘甲腺原氨酸(FT3),游离甲状腺素(FT4),超敏促甲状腺激素(sTSH)水平.用酶联免疫吸附试验(ELISA)检测血清PCⅢ水平,用放射免疫分析法(RIA)检测血清HA水平.结果 甲亢组血清FT3,FT4水平[(18.35±6.19),(76.28±23.49)pmol/L]明显高于对照组[(4.75±0.31),(16.12±3.27)pmol/L],sTSH水平[(0.15±0.07)mU/L]明显低于对照组[(3.78±0.15)mU/L],差异均有统计学意义(P＜0.01),甲低组FT3,FT4水平[(3.36±0.26),(6.37±2.19)pmol/L]均低于对照组(P＜0.05),sTSH[(44.58±13.29)mU/L]明显高于对照组(P＜0.01),亚甲低组FT3,FT4水平[(4.86±0.45),(15.26±2.78)pmol/L]与对照组比较,差异无统计学意义(P＞0.05),sTSH[(14.26±4.73)mU/L]明显高丁对照组(P＜0.01).甲亢组血清PCⅢ水平[(4.63±1.22)μg/L]明显高于甲低组[(3.64±1.12)μg/L],亚甲低组[(3.54±1.17)μg/L],对照组[(3.56±1.07)μg/L],组问两两比较差异有统计学意义(P＜0.05),而甲低组,哑甲低组,对照组PCⅢ水平任意两组间比较,差异均无统计学意义(P＞0.05),甲低组血清HA水平[(31.13±10.28)μg/L]高于甲亢组[(22.24±7.22)μg/L],亚甲低组[(22.43 4-7.99)μg/L]和对照组[(23.09±9.19)μg/L],组间两两比较差异均有统计学意义(P＜0.05),而甲低组,亚甲低组,对照组HA水平任意两组比较,差异均无统计学意义(P＞0.05).结论 在排除肝纤维化等病变的情况下,检测甲亢患者血清PCⅢ,对了解早期的心肌纤维化有重要意义,对病程较长的甲亢患者,血清HA,PCⅢ的榆测可作为早期发现肝损伤和纤维化的参考依据.     

Stem cell transplantation for autoimmune diseases

Much progress has been made in the field of haemopoietic stem cell transplants (HSCTs) for severe autoimmune disorders. Theoretical considerations, animal data and anecdotal evidence suggested some time ago that intensive immunoablation followed by autologous HSCT could restore normal immune reactivity in patients with severe autoimmune disorders. Based on a concept statement issued in 1995, two European societies, the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT) began collecting phase I/II trial data in an international collaborative network. Sufficient information from more than 350 patients allows a preliminary assessment with level three evidence. Autologous HSCTs can induce remissions in all disease categories tested so far. Remissions can be transient or durable. HSCTs are associated with significant morbidity and mortality. Treatment-related mortality (TRM) is near 10% at 1 year and is associated with the intensity of the conditioning and the stage of the disease at the time of transplant. Marked interdisease differences exist. There are few data available in haematological autoimmune diseases, more in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA) and multiple sclerosis (MS). Patient selection has been recognized as a crucial element from the phase I-II trials. Patients with advanced disease, severely compromised organ function or irreversible organ damage should not be considered as candidates for HSCT. Prospective randomized studies should now determine the value of HSCT compared to standard therapy. Such trials are ongoing for patients with systemic sclerosis (ASTIS trial--Autologous Stem Cell Transplantation International Scleroderma Trial) or are planned for patients with multiple sclerosis (ASTIMS trial--Autologous Stem Cell Transplantation International Multiple Sclerosis Trial) and rheumatoid arthritis (ASTIRA trial--Autologous Stem Cell Transplantation International Rheumatoid Arthritis Trial). More phase II data are needed for other indications such as SLE and JIA.     

Neuronal damage and neuroinflammation markers in patients with autoimmune encephalitis and multiple sclerosis

Inflammatory diseases of the central nervous system (CNS) are a diagnostic challenge to clinicians. Autoimmune encephalitis (AE) is an important diagnostic consideration in patients with CNS inflammatory disorders; despite of a wide range of neuropsychiatric symptoms it should be diagnosed as soon as possible and the patient transferred to the neurologist. We studied a group of AE patients (n?=?24) as compared to multiple sclerosis (MS, n?=?61) and control (n?=?19) groups. Detailed clinical pictures of patients are presented. We focused on relevant cerebrospinal fluid (CSF) tests like protein levels, cytosis and oligoclonal bands, neuroinflammation indices (interleukin-6, soluble receptor of IL-6, neopterin, anti-ribosomal proteins antibodies) and markers of neurodegeneration (phosphorylated neurofilament heavy chain, pNfh). Elevated neopterin level was found in AE group as compared to the MS and control groups, while protein and pNfh were increased in both AE and MS groups. In the MS group, the cytosis and soluble receptor of IL-6 were higher as compared to the control group. Anti-ribosomal proteins antibodies were increased in a single patient with AE. High levels of protein were predictive of mortality in AE patients, while IL-6 and pNfh were elevated in severe AE patients. AE patients with paraneoplastic etiology demonstrated oligoclonal bands positivity. Taken together, our results suggest the neopterin as an additional marker of autoimmune brain inflammation. Though higher levels of protein, IL-6 and pNfh were found in patients with severe disease progression and death, prognostic values of these markers should be validated in larger cohorts of patients.

     

Studies of T cell receptors in autoimmune diseases

Conclusions  The authors established a novel system for the detection of TCR clonality and examined several systemic autoimmune diseases using this system. The results strongly suggested that antigen-specific T cells are invelved in the formation of lesions in these diseases. Future studies including the identification of these antigens are expected to facilitate detailed clarification of the mechanisms of the pathogenesis of autoimmune diseases, as well as the development of antigen-specific treatments of autoimmune diseases.     

Studies of T cell receptors in autoimmune diseases

Abstract

Helical (spiral) CT provides enhanced capabilities over those with conventional CT. We use helical CT for diagnosis and preoperative simulation. This approach provides exquisite detail of the anatomical structures of the osseous tissue surrounding the hip. We describe here the findings in our patients for whom helical CT was used.     

Circulating monocyte (macrophage)-specific antibodies in patients with autoimmune thyroid diseases

We investigated the presence of circulating monocyte-specific antibodies (monocytotoxic activities) by cytotoxicity tests and also the relationships between these monocytotoxic activities and the clinical data in autoimmune thyroid diseases. Subjects of this investigation include 16 patients with Graves' disease, 20 patients with Hashimoto's thyroiditis and 10 normal controls. To obtain monocyte-rich population, peripheral blood mononuclear cells of type 0 healthy donor were incubated on culture dishes for 12 hours and dish adherent cells were separated by pipetting. These monocyte-rich population were incubated with sample sera which were previously absorbed by lymphocytes of many different kinds of HLA types to eliminate anti-lymphocyte antibodies, and thereafter cytotoxicity tests were performed by adding rabbit complements. The monocytotoxic activities were expressed by %cytotoxicities and the value of %cytotoxicity over 3.9% (mean + 4SD of %cytotoxicities of normal controls) was considered to be positive in monocytotoxic activity. The results indicate that; 1) 8 patients (50%) of Graves' disease and 10 patients (50%) of Hashimoto's thyroiditis had positive values of monocytotoxic activity. 2) These positive values of monocytotoxic activity were markedly decreased after absorption of sample sera by monocytes, and these patients who had positive values of monocytotoxic activities to allogenic monocytes also had positive values of monocytotoxic activities to autologous monocytes. 3) Patients who had positive monocytotoxic activities also had high levels of TSH receptor antibody (TRAb) and anti-microsomal antibody, besides, monocytotoxic activity was significantly correlated with levels of TRAb in Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autologous hematopoietic stem cell transplantation in autoimmune diseases

The term 'autoimmune diseases' encompasses a spectrum of diseases whose clinical manifestations and, possibly, biological features vary widely. The results of conventional treatment are considered unsatisfactory in aggressive forms, with subsets of patients having short life expectancies. Relying on wide experimental evidence and more feeble clinical data, some research groups have used autologous hematopoietic stem cell transplantation (HSCT) in the most disabling autoimmune diseases with the aim of resetting the patient's immune system. Immunoablative conditioning regimens are preferred over their myeloablative counterparts, and some form of in vivo and/or ex vivo T-cell depletion is generally adopted. Despite 15 years' experience, published controlled clinical trials are still lacking, with the evidence so far available coming from pilot studies and registry surveys. In multiple sclerosis, clinical improvement, or at least lasting disease stabilization, can be achieved in the majority of the patients; nevertheless, the worst results are observed in patients with progressive disease, where no benefit can be expected from conventional therapy. Concerning rheumatologic diseases, wide experience has been acquired in systemic sclerosis, with long-term improvements in cutaneous disease being frequently reported, although visceral involvement remains unchanged at best. Autografting has proved to be barely effective in rheumatoid arthritis and quite toxic in juvenile idiopathic arthritis, whereas it leads to clinical remission and the reversal of visceral impairment in the majority of patients with systemic lupus erythematosus. A promising indication is Crohn's disease, in which long-term endoscopic remission is frequently observed. Growing experience with autologous HCST in autoimmune diseases has progressively reduced concerns about transplant-related mortality and secondary myelodysplasia/leukemia. Therefore, a sustained complete remission seems to be within the reach of autografting in some autoimmune diseases; in others, the indications, risks and benefits of autografting need to be better defined. Consequently, the search for new drugs should also be encouraged.