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Emilia Maellaro Lucia Terzuoli Maria Romana Bacarelli Barbara Del Bello Nicola Bizzaro Brunetta Porcelli 《Autoimmunity》2020,53(5):245-252
AbstractAutoantibodies to nuclear and cytoplasmic antigens are commonly detected by indirect immunofluorescence (IIF) on HEp-2 cells, and three major staining patterns (nuclear, cytoplasmic, and mitotic) are distinguished. Here, we report an atypical cytoplasmic pattern, not described so far, observed in the serum of a patient with a controversial diagnosis of systemic lupus erythematosus (SLE). Moreover, for the first time, we have revealed the presence of autoantibodies against the microtubule-associated light-chain 3 (LC3) protein, which plays a key role in the autophagic process. The target antigen has been identified in IIF by means of a competition test using purified anti-LC3 antibodies on HEp-2 cells, and confirmed by Western blot analysis using cellular or recombinant LC3 as antigen, immunoreacted with the patient’s serum. The identification of this atypical pattern and the related autoantibody-antigen system sheds new light on autophagy, which is increasingly considered to be involved in the etiopathogenesis of autoimmune disorders, and could contribute to select more personalized therapies. 相似文献
3.
Franziska Sotzny Julià Blanco Enrica Capelli Jesús Castro-Marrero Sophie Steiner Modra Murovska Carmen Scheibenbogen 《Autoimmunity reviews》2018,17(6):601-609
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients ME/CFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for ME/CFS. Immune dysregulation in ME/CFS has been frequently described including changes in cytokine profiles and immunoglobulin levels, T- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in ME/CFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of ME/CFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in ME/CFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of ME/CFS in order to better understand and properly treat this disease. 相似文献
4.
Aberrant cell signalling in PBMCs upon IFN‐α stimulation in primary Sjögren's syndrome patients associates with type I interferon signature 下载免费PDF全文
Richard Davies Daniel Hammenfors Brith Bergum Petra Vogelsang Sonia Gavasso Johan G. Brun Roland Jonsson Silke Appel 《European journal of immunology》2018,48(7):1217-1227
Primary Sjögren's syndrome (pSS) is a complex systemic autoimmune disease with heterogeneous disease manifestations. Genetic predisposition, hormonal and environmental factors are all thought to contribute to disease etiology and pathogenesis. A better understanding of the disease pathogenesis is required in order to establish new targeted therapies. We analysed MAPK/ERK and JAK/STAT signalling networks in peripheral blood mononuclear cells (PBMCs) upon stimulation with interferon alpha 2b (IFN‐α2b) by flow cytometry to define potentially dysfunctional intracellular signalling pathways involved in disease pathogenesis. Cells derived from pSS patients displayed small but significant increases in basal phosphorylation levels of numerous signalling proteins compared to cells from healthy donors. The phosphorylation profiles following stimulation with IFNα2b differed significantly between pSS patients and healthy donors, especially regarding STAT1 Y701. PCA further grouped patients according to clinical characteristics. Type I IFN induced gene expression was found to negatively correlate with the IFN‐α2b induced phosphorylation of STAT3 S727 in T cells and positively with pSTAT1 Y701 in B cells. Increases in pSTAT1 Y701 were associated with the presence of autoantibodies. Our results indicate involvement of both STAT3 S727 and STAT1 Y701 pathways in pSS patients. Therapies targeting these pathways might therefore be beneficial for certain subgroups of patients. 相似文献
5.
Mario Ricci 《International Journal of Clinical & Laboratory Research》1987,17(4):279-297
Summary In the last few years a great deal of information on the etiopathogenetic aspects of organ-specific autoimmune diseases (OSADS)
has been obtained. It has been shown that genetic factors play an etiologic fundamental role. They are responsible for the
dysregulation of the immune system and for the target organ susceptibility which favour the onset of the diseases. Putative
environmental factors, such as viral infections, can act as initiating or precipitating events only in genetically predisposed
individuals. Immunological mechanisms capable of triggering autoimmune responses have been demonstrated. Data obtained from
experimental models and from humans suggest that the ongoing expansion of autoreactive T cells with specificity for autoantigens
(AAgs) can be considered as the main immunological event capable of inducing and maintaining the target organ damage. These
cells can activate different effector systems, i.e., autoantibody (AAb)-producing B cells, cells with cytotoxic activity,
etc., by releasing different combinations of lymphokines. In overt diseases AAbs are directly involved in the pathogenesis
of lesions due to autoimmune responses against functional molecules and cellular receptors. The pathogenesis of the common
inflammatory destructive lesions of the target organs is more complex and not yet clarified. A large proportion of T cells
present in the inflammatory infiltrates are apparently not directed to the AAgs. Most cells display cytolytic activity and
may contribute to tissue damage by releasing lymphokines which activate other cells and cascade the process. Vicious cycles,
i.e., upregulation of class II and I molecules, alterations of the cytokine network, etc., are supposed to be involved in
the maintenance of target organ lesions. 相似文献
6.
用重组M2三联体抗原建立原发性胆汁性肝硬化免疫检测法 总被引:5,自引:2,他引:5
目的 建立原发性胆汁性肝硬化(PBC)特异性免疫学检测方法。方法 在重组质粒表达的基础上,用亲和层析进一步纯化重组蛋白后,用酶免疫吸附法检测M2抗体。结果 在PBC组11例患者哈部检出M2抗体,阳性率为1005,而非PBC组75例患者中无一检出M2抗体,本法与病理检查和临床诊断的相关性有非常显著意义(P<0.01)。结论 本法检测M2抗体有较好的敏感性及特异性,为PBC的早期发现和临床诊断提供了有力的工具。 相似文献
7.
抗细胞膜DNA抗体在三种自身抗体阴性系统性红斑狼疮中的诊断价值 总被引:1,自引:0,他引:1
目的 研究抗细胞膜DNA(mDNA)抗体在抗Sm抗体、抗双链DNA(dsDNA)抗体和抗核小体抗体(AnuA)等特异性自身抗体阴性的系统性红斑狼疮(SLE)中的诊断意义。方法 随机选择145例SLE患者。以Raji细胞为底物,采用间接免疫荧光法检测SLE患者血清抗mDNA抗体和抗dsDNA抗体,采用免疫印迹法检测抗Sm抗体,酶联免疫吸附法测定AnuA。分析抗mDNA抗体在其他特异性自身抗体阴性SLE患者中的诊断价值。结果 抗mDNA抗体在SLE中的阳性率为69.7%,明显高于抗Sm抗体(19.7%)、抗dsDNA抗体(31.9%)和AnuA(45.8%,均P〈0.01)。在抗dsDNA抗体阴性的SLE患者中,抗mDNA抗体的阳性率达64.3%;在抗Sm抗体阴性的SLE患者中,抗mDNA抗体的阳性率为70.2%;而AnuA阴性的SLE患者中,抗mDNA抗体的阳性率为60.3%。结论 抗mDNA抗体是一种敏感性较高的SLE血清学标志之一,尤其对抗Sm抗体、抗dsDNA抗体或AnuA阴性SLE的诊断具有重要参考意义。 相似文献
8.
甲状腺过氧化物酶抗体和甲状腺球蛋白抗体阳性临界值的确定及其临床意义 总被引:11,自引:0,他引:11
目的 确定甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TgAb)的阳性临界值,并探讨这两种抗体出现的临床意义。方法 1999至2000年对3个中国农村社区3761名进行甲状腺疾病流行病学调查,采血、尿标本,同时行甲状腺B超检查,2004年对该人群进行随访。所有血清标本均用固相化学发光酶免疫分析法测定TPOAb和TgAb及促甲状腺激素(TSH)水平。结果 甲状腺功能及形态正常人群(2437名)TPOAb和TgAb的95%正常可信区间上限分别为37.8IU/ml和38.6IU/ml。总人群(3761名)中随TPOAb浓度的升高发生TSH升高(〉4.8IU/m1)或降低(〈0.3IU/m1)的比率也呈阶梯式增加,但仅当TPOAb≥50IU/ml时,发生TSH异常率比TPOAb438IU/ml者的差异有统计学意义(P〈0.01)。同样TgAb≥40IU/ml时,发生TSH异常率比TgAb≤39IU/ml者差异也有统计学意义(P〈0.01)。当TPOAb以50IU/ml和TgAb以40IU/ml为阳性临界值时,总人群中TPOAb和TgAb的阳性率女性(11.71%、11.21%)显著高于男性(4.07%、2.68%)。抗体阳性人群的TSH水平显著高于抗体阴性组(P〈0.05)。原TSH正常抗体阳性人群(515名)随访发现甲状腺功能减退症的发生率显著高于抗体阴性人群(P〈0.05)。结论 用高灵敏性化学发光酶免疫分析法在尿碘中位数为100~600μg/L的普通人群中确定TPOAb和强Ab的阳性临界值分别为50IU/ml和40IU/ml。甲状腺自身抗体TPOAb和TgAb阳性是发生甲状腺功能损伤的重要危险因素。 相似文献
9.
Invariant natural killer T cells in lupus patients promote IgG and IgG autoantibody production 下载免费PDF全文
Lei Shen Hong Zhang Maria Caimol Claudia J. Benike Eliza F. Chakravarty Samuel Strober Edgar G. Engleman 《European journal of immunology》2015,45(2):612-623
IgG autoantibodies, including antibodies to double‐stranded DNA (dsDNA), are pathogenic in systemic lupus erythematosus (SLE), but the mechanisms controlling their production are not understood. To assess the role of invariant natural killer T (iNKT) cells in this process, we studied 44 lupus patients. We took advantage of the propensity of PBMCs from patients with active disease to spontaneously secrete IgG in vitro. Despite the rarity of iNKT cells in lupus blood (0.002–0.05% of CD3‐positive T cells), antibody blockade of the conserved iNKT TCR or its ligand, CD1d, or selective depletion of iNKT cells, inhibited spontaneous secretion of total IgG and anti‐dsDNA IgG by lupus PBMCs. Addition of anti‐iNKT or anti‐CD1d antibody to PBMC cultures also reduced the frequency of plasma cells, suggesting that lupus iNKT cells induce B‐cell maturation. Like fresh iNKT cells, expanded iNKT‐cell lines from lupus patients, but not healthy subjects, induced autologous B cells to secrete antibodies, including IgG anti‐dsDNA. This activity was inhibited by anti‐CD40L antibody, as well as anti‐CD1d antibody, confirming a role for CD40L‐CD40 and TCR‐CD1d interactions in lupus iNKT‐cell‐mediated help. These results reveal a critical role for iNKT cells in B‐cell maturation and autoantibody production in patients with lupus. 相似文献
10.
目的:分析抗组胺耐药慢性荨麻疹患者的甲状腺自身抗体及甲状腺激素水平变化与意义。方法选取抗组胺耐药慢性荨麻疹患者40例为观察组,同期在我院做体检的健康者40例为对照组,检测两组受试者的甲状腺自身抗体和甲状腺各项功能指标,并进行自体血清皮肤试验(ASST)。结果观察组的促甲状腺素受体抗体(TRAb)、抗甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TGAb)等甲状腺自身抗体指标及ASST的阳性率明显高于对照组,差异均有统计学意义(P<0.05);观察组患者的游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)、总甲状腺激素(TT4)、总三碘甲状腺原氨酸(TT3)、超敏促甲状腺素(TSH)等指标明显高于对照组,差异均有统计学意义(P<0.05)。结论抗组胺耐药慢性荨麻疹患者甲状腺发病与甲状腺自身抗体密切相关,血清出现各种自身抗体表达及甲状腺激素水平异常,值得临床深入研究。 相似文献