共查询到20条相似文献,搜索用时 15 毫秒
1.
Jonsson MV Salomonsson S Øijordsbakken G Skarstein K 《Scandinavian journal of immunology》2005,62(6):552-559
The aim of this study was to investigate serum levels of soluble E-cadherin (sE-cadherin) in relation to lymphocytic organization and to characterize the expression of E-cadherin and integrin αEβ7/CD103 in salivary gland epithelium of patients with Sjögren's syndrome (SS). Serum levels of sE-cadherin were significantly increased in SS compared to non-SS and nonsignificantly in germinal centre (GC)+ compared to GC– patients. Membrane-bound E-cadherin was detected on the majority of acinar and ductal epithelial cells in both SS and non-SS. αEβ7/CD103-positive cells were found scattered in focal infiltrates and GC, and in small clusters close to ductal and acinar epithelium at an increased level in SS compared to non-SS. Interestingly, E-cadherin-positive cells were detected randomly dispersed in focal lymphocytic infiltrates in 10/21 patients. By double-labelling, the cells with the E-cadherin-positive component were identified as CD68+ macrophages. Elevated serum levels of sE-cadherin indicate an increased epithelial cell turnover and shedding, and sE-cadherin deserves further analysis as a potential diagnostic tool for SS. 相似文献
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Basset C Durand V Mimassi N Pennec YL Youinou P Dueymes M 《Scandinavian journal of immunology》2000,51(3):307-311
Despite the indisputable role of immunoglobulin (Ig)A in the pathogenesis of primary Sjögren syndrome (pSS), the causative abnormality remains largely unknown. As an extension of our report that IgA is oversialylated in this disease, the thrust of the present study was to measure the sialyltransferase (ST) activity in B lymphocytes. ST containing lysates of B cells from 17 pSS patients and 10 controls, were obtained using a combination of detergents, and incubated with affinity purified IgA that had been previously desialylated. The deposition of cytidine 5′ monophosphate sialic acid (SA) by ST from B cells onto IgA was detected by two ELISA based upon the use of biotinylated lectins (Sambucus nigra agglutinin which is specific for α2–6 SA and Maackia amurensis which is specific for α2–3 SA). In parallel, the amount of SA on IgA from ten of the 17 patients and eight of the 10 controls was assayed using the same method. An excess of α2–3 and α2–6 SA on IgA was found in those patients with excessive activity of α2–3 and α2–6 ST. Thus, IgA hypersialylation in pSS patients may result from undue activity of ST. 相似文献
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We studied the proportions of Th1 and Th2 cells in peripheral blood of 15 patients with primary Sj?gren's syndrome (p-SS), by using a procedure to enumerate the cells synthesizing cytokines such as INF-gamma or IL-4 in cytoplasm of CD4+ lymphocytes. The frequency of Th1 (INF-gamma containing) cells in p-SS patients was significantly reduced as compared to normal control (20.57+/-7.48% vs 28.78+/-11.56%, p < 0.05), while that of Th2 (IL-4 containing) cells was not different from normal control (3.33+/-0.98% vs 2.85+/-1.88%). The ratio of Th1 to Th2 cells in p-SS patients was significantly decreased as compared to normal control (6.60+/-3.15 vs 11.55+/-6.72, p < 0.05). There was no difference in frequency of Th1 or of Th2 cells between 8 patients given small amounts of prednisolone (PSL) and 7 patients not given PSL (21.44+/-9.39% vs 19.57+/-5.05%, 3.12+/-0.80% vs 3.56+/-1.17%). The percentage of Th1 cells was not different between 7 patients with glandular symptoms (G) and 8 patients with extraglandular symptoms (EG) (18.61+/-9.63% vs 22.27+/-5.02%). Although the frequency of Th2 cells was higher in EG-patients than that in G-patients (3.84+/-0.78% vs 2.74+/-0.86%) with tendency of elevated IgG level in sera, the ratio of Th1 to Th2 cells was not different among them (6.26+/-2.84 vs 6.99+/-3.64). These results suggest that the reduced ratio of Th1 to Th2 cells is essential and is related to the dysfunction of cellular immunity in p-SS. 相似文献
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Dong L Masaki Y Takegami T Jin ZX Huang CR Fukushima T Sawaki T Kawanami T Saeki T Kitagawa K Sugai S Okazaki T Hirose Y Umehara H 《Clinical and experimental immunology》2007,150(2):279-284
The aim of this study was to clarify the nature of the clonal lymphocyte infiltration in Sjögren''s syndrome (SS) patients associated with lymphoproliferative disorders. We examined B cell clonality in lymphoproliferative tissues from six primary SS patients associated with lymphoproliferative disorders or lymphoma by cloning and sequencing of the gene rearrangement of the immunoglobulin heavy chain complementarity determining region 3 (IgVH–CDR3). Three patients with sequential observation showed progressional clonal expansion with the presence of the same subclone in different tissues during the course of disease. Among them, one patient developed mucosa-associated lymphoid tissue (MALT) lymphoma in glandular parotid. The other three SS patients concomitant with malignant B cells lymphomas showed different clonal expansion of B cells between nodal sites and salivary glands. The cloanality analysis indicated that monoclonal B cell population could spread from one glandular site to another site during the course of SS, suggesting that the malignant clone may arise from the general abnormal microenvironment, not restricted to the glandular tissue, in some SS patients. 相似文献
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Primary Sj?gren's syndrome (pSS) is an autoimmune exocrinopathy characterized by chronic inflammation and destruction of the salivary and lacrimal glands. B- and T- lymphocyte infiltrations in the salivary glands with development of germinal center-like structures are characteristic for pSS. Overexpression of soluble factors, such as interferon α (IFNα) and B-cell activating factor (BAFF), are supposed to be important factors in the initiation and continuation of this disorder. The efficacy and success of B-cell depleting therapy in reducing disease activity in pSS patients for about six to nine months supports the notion that B-cells are major key players in disease manifestation of pSS. In addition to B-cells, also Th-cells (mainly Th17) seem to be involved in the pathogenetic process. In this review, we will discuss recent research findings regarding the cytokines IFNα and BAFF as wells as the role of B- and T-cells in pSS. Emphasis will be put on the impact of B-cell depletion therapy as well as on the presumed impact of therapies aimed for targeting BAFF, either as a sole modality or as a combined treatment with B-cell depletion. 相似文献
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《Autoimmunity》2013,46(7):547-555
We have previously shown that patients with primary Sjögren's Syndrome (pSS) show a significant reduction of autoantigen specific CD27+ memory B cells and an abnormally elevated level of autoantibody producing plasma cells in peripheral blood (PB) compared to controls. Because both memory B cells and plasma cells have been detected in salivary glands (SG) of pSS patients, we aimed to study the B cell pattern in SG biopsies. Double immunohistochemical staining of CD20 and CD27 was carried out on paraffin-embedded SG tissue from 10 pSS patients to distinguish CD20+/CD27+ memory B cells, and identify the CD20+ glandular B cell zones (BCZ). Given that plasma blasts and plasma cells are CD27++ and CD20? , additional CD138 single staining of serial sections allowed the distinction of CD27++/CD138? plasma blasts located within the BCZ from CD27++/CD138+ plasma cells that were found mostly on the periphery of the BCZ and also observed interstitially. Both BCZ and the memory B cell populations were then quantified. Contrary to what has been reported earlier through immunoflourescent staining of memory B cells in SG tissue, we have shown that there is a low number of memory B cells located within the glandular BCZ. Plasma blasts and plasma cells, however, were more abundant in the SG. Together our findings suggest that these low numbers of memory B cells in both PB and SG of pSS patients may be the result of activation of these cells into plasma cells at the site of inflammation. 相似文献
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Neurophysiological assessment of peripheral neuropathy in primary Sjögren's syndrome 总被引:1,自引:0,他引:1
Peripheral nervous system complications are rare in patients with primary Sjögren's syndrome. We investigated a group of six women aged 43–64 years who complained of pain and sensory symptoms. Conventional neurophysiological tests reflecting large nerve fiber function revealed normal motor conduction in all patients, whereas sensory nerve action potentials were absent in two. On the other hand, quantitative thermometry and autonomic nerve function tests indicating small nerve fiber function were more sensitive in the assessment of nerve dysfunction; these showed abnormalities in all cases. Vibrametry showed dysfunctions in four patients. The latter methods possess great sensitivity in discovering sensory disturbances. Neurophysiological assessment of the sensory and autonomic nervous system demonstrating sensory neuropathy contributes to early diagnosis of primary Sjögren's syndrome.Abbreviations HRV
heart rate variation
- PNS
peripheral nervous system
- pSS
primary Sjögren's syndrome
- SSEP
short-latency somatosensory evoked potentials
- SSR
sympathetic skin response
- SuCV
sudomotor nerve conduction velocity 相似文献
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Julie K Karp Esen K Akpek Robert A Anders 《International journal of clinical and experimental pathology》2010,3(6):582-586
Based on the revised criteria of the American-European Consensus Group, we retrospectively established the diagnosis of primary or secondary Sjögren''s syndrome for 202 patients referred to a Sjögren''s syndrome clinic. Of these, 58 patients and 8 patients fulfilled criteria for primary and secondary Sjögren''s syndrome, respectively. Of the 58 patients with primary Sjögren''s syndrome, one (1.7%) had definite autoimmune hepatitis, as defined by the International Autoimmune Hepatitis Group diagnostic criteria. One additional symptomatic patient who did not fulfill criteria for primary Sjögren''s syndrome had definite autoimmune hepatitis. None of the patients with secondary Sjögren''s syndrome had definite autoimmune hepatitis. Two (1%) of the 194 patients with primary Sjögren''s syndrome or clinical symptoms had primary biliary cirrhosis. These values are lower than those reported by prior studies with smaller patient populations and likely represent a more accurate estimate of the true prevalence of these diseases in patients with primary Sjögren''s syndrome. 相似文献
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Downie-Doyle S Lester S Bardy P Gordon T Rischmueller M Pile K 《Genes and immunity》2002,3(Z1):S63-S65
The immunoglobulin kappa (Km) light chain gene is polymorphic and is believed to play a role in the pathology of infectious and autoimmune diseases. Polymorphisms within the constant region of the Km gene encode three alleles designated Km1, Km1,2 and Km3. Previous studies using serological detection of Km allotypes reported associations between specific Km allotypes, systemic lupus erythematosus and the presence of anti-La antibodies, yet these findings were not confirmed in other studies. In order to more precisely define any associations between Km alleles and anti-Ro/La antibodies we used the polymerase chain reaction and restriction fragment length polymorphisms for Km genotyping in a large cohort of patients with primary Sj?gren's syndrome (SS). No associations were observed between specific Km alleles and primary SS when compared with a control population, nor within serologically defined subsets of SS patients. We conclude that Km alleles are not associated with primary SS or the Ro/La autoantibody response. 相似文献
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Major breakthroughs have occurred with classification of B-cells into populations and subpopulations. With respect to their expression of CD5, they comprise the B1 and B2 populations, with the former further divided into B1a and B1b subpopulations. The oncologic process starts from transitional type 1 (T1) and T2 immature B-cells, through marginal zone or germinal center B-cells, ending up with memory B-cells and plasma cells (PCs). They may also be categorized based on their functional commitment with polarized B effector (Be)1 and Be2, with B-activating factor of the tumor-necrosis factor-producing B-cells, and with short-lived and long-lived PCs. Such a seemingly homogeneous family of cells has thus turned out to be a genuine mosaic of B-lymphocyte subsets. 相似文献
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T. Shimizu H. Nakamura A. Takatani M. Umeda Y. Horai S. Kurushima T. Michitsuji Y. Nakashima A. Kawakami 《Clinical and experimental immunology》2019,196(1):39-51
The aim of this study was to determine the expressions of Toll-like receptors (TLRs) 7–9 and type I interferon (IFN) signal in labial salivary glands (LSGs) and cultured salivary gland epithelial cells (SGECs) from primary Sjögren's syndrome (pSS) patients. We performed an immunohistochemistry analysis of LSGs from 11 patients with pSS as defined by American–European Consensus Group classification criteria and five healthy subjects. The pSS patients' SGECs were analyzed by immunofluorescence and western blotting. IFN-α expression was examined by immunosorbent assay and flow cytometry. Mononuclear cells (MNCs) from pSS patients' LSGs showed TLR-7-dominant expression. B cells, plasma cells and plasmacytoid dendritic cells (pDCs) co-expressed with TLR-7. Myeloid differentiation primary response gene 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6) and interferon regulatory factor 7 (IRF7) co-expressed with the pDC marker CD303 in LSGs. Ducts from pSS patients dominantly expressed TLR-7, and TLR-7 in the ducts co-expressed with MyD88, TRAF6 and IRF7. Type I IFNs including IFN-α and IFN-β were detected in MNCs and ducts in pSS patients' LSGs. Increased TRAF6 expression and the nuclear translocation of IRF7 in SGECs were detected by immunofluorescence following loxoribine (a TLR-7 ligand) stimulation despite IFN-β pretreatment. Western blotting showed increased TRAF6 expression in SGECs following IFN-β and loxoribine stimulation. Although no increase in IFN-α was detected in supernatant from stimulated SGECs, the IFN-α in supernatant from stimulated peripheral blood pDCs from pSS patients was significantly increased. Our findings suggest that TLR-7 is dominantly expressed in both MNCs and ducts with downstream signals for type I IFNs, indicating that TLR7-dominant innate immunity is related to the development of sialadenitis in pSS. 相似文献
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Korman BD Alba MI Le JM Alevizos I Smith JA Nikolov NP Kastner DL Remmers EF Illei GG 《Genes and immunity》2008,9(3):267-270
Single nucleotide polymorphisms in the STAT4 gene have recently been shown to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Primary Sj?gren's syndrome (pSS) is a related autoimmune disease thought to have a pathogenesis similar to these diseases. To test the hypothesis that the variant haplotype of STAT4 seen in RA and SLE is also associated with pSS, we genotyped rs7574865, the most strongly disease-associated SNP in the variant STAT4 haplotype, in 124 Caucasian pSS subjects and compared them to 1143 Caucasian controls. The disease-associated T allele was more common in chromosomes of the pSS patients (29.6%) than in controls (22.3%), leading to a P-value for association of 0.01. These results implicate polymorphisms in the STAT4 gene in the pathogenesis of pSS. 相似文献
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Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjögren's syndrome, rheumatoid arthritis and healthy controls
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Eriksson P Andersson C Ekerfelt C Ernerudh J Skogh T 《Clinical and experimental immunology》2004,137(3):617-620
Primary Sjögren's syndrome (SS) is characterized by inflammation in salivary and lachrymal glands, with a local predominance of Th1‐like cytokines, as well as the pleiotropic cytokine interleukin (IL) 18. High serum levels of polyclonal IgG are common, with a subclass imbalance in which IgG1 is increased and IgG2 is normal or low. IL‐18 is also of pathogenetic importance in rheumatoid arthritis. In the present study we looked for any relationship between serum IL‐18 as well as transforming growth factor (TGF) β1 versus IgA, IgM, and IgG subclass levels in SS (n = 16), rheumatoid arthritis (RA) (n = 15), and healthy controls (n = 15). SS was defined by the revised American‐European classification criteria. IL‐18 and TGF‐β1 were analyzed with enzyme immunoassays (EIA), and IgG1, IgG2 and IgG3 by single radial immunodiffusion. In the composite group of RA, SS and normal controls, IgG1 and IL‐18 were related (R = 0·52, P = 0·0005). No relation was found neither between IL‐18 versus IgG2, IgG3 or IgA, nor between serum TGF‐β1 versus any of the immunoglobulins. Since serum levels of IL‐18 are related to serum IgG1, IL‐18 may be of importance for IgG1 switch and/or release. 相似文献
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Clinical significance of autoantibodies recognizing Sjögren's syndrome A (SSA), SSB, calpastatin and alpha-fodrin in primary Sjögren's syndrome
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Goëb V Salle V Duhaut P Jouen F Smail A Ducroix JP Tron F Le Loët X Vittecoq O 《Clinical and experimental immunology》2007,148(2):281-287
The aim of our study was (i) to compare the clinical and biological characteristics of 148 (137 women, 11 men) primary Sjögren's syndrome (pSS) patients at diagnosis as a function of their sex and (ii) to assess the prognostic value of anti‐calpastatin and anti‐alpha‐fodrin autoantibodies. In addition, the presence of anti‐nuclear antibodies (ANA), anti‐52‐ and 60‐kDa Sjögren's syndrome A (SSA), anti‐Sjögren's syndrome B (SSB), anti‐cyclic citrullinated peptide (CCP) antibodies and rheumatoid factors (RF) of IgA, IgG and IgM isotypes was sought in sera collected at pSS onset. Raynaud's syndrome, significantly more frequent in women, was the only systemic manifestation of pSS whose frequency differed significantly as a function of the patient's sex (P = 0·02). ANA (P = 0·001) and anti‐60‐kDa SSA autoantibodies (P = 0·03) were significantly more common in women, while men never synthesized detectable levels of anti‐SSB, anti‐calpastatin or IgG anti‐alpha‐fodrin autoantibodies. In addition, anti‐CCP autoantibodies were found in low percentages of pSS patients (4% F/18% M). The absence of autoantibodies does not exclude the diagnosis of pSS in men that will be based mainly on the anatomopathological findings of a minor salivary gland biopsy. Positivity of anti‐60‐kDa SSA, anti‐SSB, anti‐calpastatin, IgA and IgG anti‐alpha‐fodrin antibodies is not associated with pSS clinical and biological severity. 相似文献
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Nakagawa Y Kataoka H Kurita T Nakagawa H Yasuda S Horita T Atsumi T Koike T 《Nihon Rinshō Men'eki Gakkai kaishi》2012,35(1):75-80
Sj?gren's syndrome (SS) is a systemic autoimmune disorder characterized by profound lymphocytic infiltration into the lacrimal and salivary glands, thereby diminished secretory function. B cell hyper-activation is a predominant feature of SS related to hypergammaglobulinemia and production of autoantibodies. The adaptor molecule NF-kB activator 1 (Act1) plays an important role in the homeostasis of B cells by attenuating CD40 and B cell-activating factor belonging to the tumor necrosis factor family receptor (BAFFR) signaling. Act1-deficient mice develop autoimmune manifestations similar to SS, which are hypergammaglobulinemia, high levels of anti-SSA and anti-SSB autoantibodies. In this study, to investigate the role of Act1 in the pathogenesis of SS, we examined Act1mRNA expressions in B cells from patients with SS and discussed the association of Act1 with parameters and clinical manifestations of SS. We showed the low level of Act1mRNA expression in patients with SS and reciprocal association of Act1 with serum IgG level. Diminished Act1mRNA expression in SS may be associated with B cell hyperactivity and elevated immunoglobulin production in SS by uncontrolled B cell activation signal through CD40 and BAFFR. 相似文献
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Beroukas D Hiscock J Gannon BJ Jonsson R Gordon TP Waterman SA 《Laboratory investigation; a journal of technical methods and pathology》2002,82(11):1547-1552
Salivary and lacrimal gland secretions are reduced in primary Sj?gren's syndrome (pSS). Aquaporins (AQPs) are involved in transmembrane water transport, and different isoforms show specific cellular and subcellular distributions in salivary and lacrimal glands. Changes in expression of AQP molecules have therefore been suggested to contribute to the glandular dysfunction in pSS. AQP-5 is present in the apical membrane of acinar cells, where it mediates fluid outflow; however, we have recently shown that its expression is not altered in pSS. We therefore studied whether expression of other isoforms of AQP would be altered in pSS. Using high-resolution confocal microscopy, we determined the distribution of AQP-1 and AQP-3 in labial salivary gland biopsies from 11 patients with pSS and 9 healthy controls. AQP-1 is present in myoepithelial cells surrounding acini, and its expression in these cells was decreased by 38% in pSS glands. By contrast, expression of AQP-1 in endothelial cells of nonfenestrated capillaries was not altered in pSS. AQP-3 was expressed in the basolateral membrane of acinar epithelial cells, and its expression was not altered in disease. We therefore conclude that AQP-1 expression in myoepithelial cells is selectively down-regulated in pSS and that myoepithelial cell dysfunction may play a crucial role in the pathology of this disease. 相似文献