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ID PMID Title PublicationDate abstract
16932699 Mechanisms of Disease: primary Sjögren's syndrome and the type I interferon system. 2006 May Sjögren's syndrome is a chronic autoimmune disease of largely unknown etiology and pathogenesis. The salivary and lacrimal glands are the main target organs, and key cells and molecules involved in the autoimmune process have been detected in these glands. Chemokines, expressed by epithelial cells, can attract T cells and dendritic cells that produce proinflammatory cytokines, which stimulate the immune response and induce apoptosis in the acinar and ductal epithelial cells. The autoantigens SSA and SSB are translocated to the apoptotic blebs and trigger infiltrating B cells to produce autoantibodies against SSA and SSB. Germinal-center-like structures can form within glandular lymphocyte foci, facilitating the antigen-driven B-cell activation. Many of the autoimmune mechanisms described above can be induced by type I interferon (IFN), and activation of this system in patients with Sjögren's syndrome has been described. A possible scenario is that an initial viral infection induces type I IFN production in salivary glands with a subsequent activation of the adaptive immune system. Resultant autoantibodies form nucleic-acid-containing immune complexes that can trigger prolonged type I IFN production, leading to a self-perpetuating autoimmune reaction. Several potential therapeutic targets for Sjögren's syndrome exist within the type I IFN system.
16670339 The Sjogren's syndrome-associated autoantigen Ro52 is an E3 ligase that regulates prolifer 2006 May 15 Patients affected by Sjögren's syndrome and systemic lupus erythematosus (SLE) carry autoantibodies to an intracellular protein denoted Ro52. Although the serologic presence of Ro52 autoantibodies is used clinically for diagnostic purposes, the function of the protein or why it is targeted as an autoantigen in several rheumatic conditions has not been elucidated. In this study, we show that the expression of Ro52 is significantly increased in PBMC of patients with Sjögren's syndrome and SLE, and demonstrate that Ro52 is a RING-dependent E3 ligase involved in ubiquitination. Overexpression of Ro52, but not of Ro52 lacking the RING domain, in a mouse B cell line lead to decreased growth in steady state and increased cell death after activation via the CD40 pathway. The role of Ro52 in activation-mediated cell death was further confirmed as a reduction in Ro52 expression restored cell viability. These findings suggest that the increased expression of the Ro52 autoantigen in patients may be directly involved in the reduced cellular proliferation and increased apoptotic cell death observed in Sjögren's syndrome and SLE, and may thus contribute to the autoantigenic load and induction of autoimmune B and T cell responses observed in rheumatic patients.
16881116 Characterization and differentiation of autoimmune versus viral liver involvement in patie 2006 Aug OBJECTIVE: To analyze the prevalence and clinical significance of liver involvement in patients with Sjögren's syndrome (SS), focusing on the characterization and differentiation of autoimmune versus chronic viral liver disease. METHODS: We investigated liver involvement (clinical signs, analytical data, chronic viral infections, and autoantibodies) in 475 consecutive patients with SS. All patients fulfilled 4 or more of the 1993 European Community Study Group criteria for SS. RESULTS: Liver involvement was detected in 129 (27%) patients. After ruling out chronic illnesses or use of hepatotoxic drugs, the main etiologies were chronic viral liver disease in 64 (13%) cases [chronic hepatitis C virus (HCV) infection in 63 and HBV infection in one] and autoimmune liver diseases in 24 (5%; primary biliary cirrhosis in 16 patients and type-1 autoimmune hepatitis in 8). The analytical liver profile was not useful in differentiating between viral and autoimmune liver disease. In contrast, patients with SS and autoimmune liver disease presented higher mean values of erythrocyte sedimentation rate (p = 0.044), circulating gammaglobulins (p = 0.007), and a higher prevalence of antinuclear antibodies (p < 0.001), antimitochondrial antibodies (p < 0.001), anti-smooth muscle antibodies (p = 0.026), anti-Ro/SSA (p < 0.001), and anti-La/SSB (p = 0.01), while patients with chronic viral liver disease had a higher frequency of cryoglobulinemia (p < 0.001) and hypocomplementemia (p < 0.001). CONCLUSION: Chronic viral liver disease (associated overwhelmingly with HCV) was the main cause of liver involvement in our patients with SS, with a prevalence of 13%, nearly 3-fold greater than that observed for autoimmune liver involvement. The immunological pattern played a key role in the differentiation of viral (predominance of cryoglobulins and low complement levels) and autoimmune (higher frequency of autoantibodies) liver involvement.
16802363 Systemic sclerosis-associated Sjögren's syndrome and relationship to the limited cutaneou 2006 Jul OBJECTIVE: To determine the prevalence of sicca symptoms and Sjögren's syndrome (SS) in a 2-center prospective series of patients with systemic sclerosis (SSc), using the American-European Consensus Group criteria for SS. METHODS: Consecutive SSc patients hospitalized for followup care were evaluated for sicca symptoms. When the initial clinical evaluation yielded positive findings, a labial salivary gland biopsy was performed; histologic analysis evaluated focal lymphocytic sialadenitis and/or glandular fibrosis. Computed tomography and respiratory function tests were used to assess pulmonary fibrosis. RESULTS: We included 133 SSc patients (mean +/- SD age 55 +/- 13 years; mean +/- SD disease duration 6.5 +/- 6 years). Eighty-one patients had limited cutaneous SSc (lcSSc). Ninety-one patients (68%) had sicca syndrome. Histologic analysis revealed fibrotic involvement in 50 of these 91 patients, but labial salivary gland fibrosis was not associated with any organ involvement we evaluated. Nineteen of the 133 patients (14%) had SS. In this subgroup, lcSSc was present at a significantly higher frequency (18 of 19 patients) than in the remaining patients with sicca syndrome (39 of 72 patients) and the patients without sicca syndrome (24 of 42 patients). This subgroup also had a significantly higher frequency of anticentromere antibodies (18 of 19 patients) than did the remaining patients with sicca syndrome (19 of 72 patients) and the patients without sicca syndrome (5 of 42 patients). In addition, this subgroup had a significantly lower prevalence of pulmonary fibrosis (2 of 19 patients) than did the remaining patients with sicca syndrome (29 of 72 patients) and the patients without sicca syndrome (19 of 42 patients). CONCLUSION: There was a 68% prevalence of sicca syndrome in this prospective series of SSc patients. Sicca syndrome was related primarily to glandular fibrosis, the hallmark of SSc. The prevalence of secondary SS, as defined by the American-European Consensus Group criteria, was 14% and was markedly associated with lcSSc. We believe that lcSSc should be regarded as a specific autoimmune subgroup of SSc.
18301381 Fetal Hox11 expression patterns predict defective target organs: a novel link between deve 2008 May Developmental biology has long been ignored in the etiology and diverse manifestations of autoimmune diseases. Yet a role for development is suggested by intriguing overlaps in particular organs targeted in autoimmune diseases, in this case type 1 diabetes and Sjogren's syndrome. Patients with type 1 diabetes have high rates of co-occurring Sjogren's syndrome, and both conditions are associated with hearing loss and tongue abnormalities. All of these co-occurrences are found in organs tracing their lineage to the developmental transcription factor Hox11, which is expressed in embryonic cells destined for the pancreas, salivary glands, tongue, cranial nerves and cochlea. To determine whether development contributes to autoimmunity, we compared four target organs in NOD mice (an animal model for type 1 diabetes and Sjogren's syndrome) with NOD-SCID mice (which lack lymphocytes) and normal controls. We examined the structure and/or function of the cochlea, salivary glands, pancreas and tongue at early time points after birth. Before the usual time of the onset of type 1 diabetes or Sjogren's syndrome, we show that all four Hox11-derived organs are structurally abnormal in both NOD mice and NOD-SCID mice versus controls. The most striking functional defect is near complete hearing loss occurring before the normal time of the onset of autoimmunity. The hearing loss is associated with severe structural defects in the cochlea, suggesting that near-deafness occurs independent of autoimmune attack. The pancreas and salivary glands are also structurally abnormal in NOD and NOD-SCID mice, but they are functionally normal. This suggests that autoimmune attack of these two organs is required for functional failure. We conclude that a developmental lineage of cells contributes to autoimmunity and predicts which organs may be targeted, either structurally and/or functionally. Taken together, our findings challenge the orthodoxy that autoimmunity is solely caused by a defective immune system.
17145372 Clinical, serologic, and genetic profiles of patients with associated Sjögren's syndrome 2006 Nov Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) can coexist in patients. The aim of this study was to investigate the clinical, laboratory, and serologic features of the association of the two diseases. Data from 56 patients having both SS and SLE were analyzed, with special emphasis on their clinical, laboratory, and serologic features. Data from 50 patients with SLE and 50 patients with SS served as control subjects. The mean age in SS-SLE group was lower than in patients with SS but higher than patients with SLE. When SLE and SS were associated, presence of rheumatoid factor was less frequent, whereas anti-Ro/SS-A, anti-La/SS-B, antinuclear, anti-DNA, and antiphospholipid autoantibodies appeared more often. Antiphospholipid syndrome, anemia, leucopenia, and lymphopenia were more frequent in the associated disease than in patients with SS alone. In SS-SLE patients, pulmonary, renal, skin, central nervous system involvement, and serositis occurred more often than in patients with SS alone. Thyroiditis, autoantibodies to Ro/SS-A, La/SS-B and ds-DNA was more frequent in the SS-SLE group than in patients with SLE. Genetic background of the patients did not differ significantly. In conclusion, characteristic clinical, laboratory and serologic features distinguish between the association of SS and SLE and the primary forms of these two diseases.
16735112 Extranodal marginal zone B-cell lymphoma of the lung in Sjögren's syndrome patients: reap 2007 Jan BACKGROUND: Primary Sjögren's syndrome (pSs) is an autoimmune rheumatic disease that may express in a small number of patients a spectrum of lymphoproliferative diseases. The aim of this study was to describe clinical, imaging and pathology features of the extranodal marginal zone B-cell lymphoma (MZCL) of the lung of mucosa-associated lymphoid tissue (MALT) type in patients with pSs. METHODS: All patients (N=10) with biopsy proven MZCL of the lung of MALT type diagnosed in a tertiary teaching hospital during the last 7 years were studied. RESULTS: Seven patients had pSs. Almost all patients presented an indolent clinical course, contrasting strongly with the spectacular radiological findings in both chest roentgenograms and computed tomography. Pathology infiltration patterns observed were either nodular, peribronchial-perivascular, alveolar, or interstitial. Immunohistochemical study in all cases showed B cell phenotypes. Immunoglobulin light chain restriction was demonstrated in all patients. Monoclonal IgM(kappa) was evident in 5/7, IgM(lambda) in 1/7 and IgG (kappa) in 1/7 of patients. CONCLUSIONS: Lung MZCL associated with pSs are characterized by an important dissociation between clinical expression and radiological pattern. Clinical presentation and imaging features are not specific. Therefore, histologic documentation is mandatory to ensure diagnosis. Various chemotherapeutic agents in combination with rituximab lead to partial or complete remission in the majority of patients.
18625620 Severe alterations in expression and localisation of {alpha}6{beta}4 integrin in salivary 2009 Jun OBJECTIVES: In salivary glands from patients with Sjögren syndrome, overexpression of laminins 1 and 5 and disorganisation of the acinar basal lamina have been reported. Laminin 5 mediates association of the basal lamina with epithelial cells by forming adhesion complexes upon interaction with alpha6beta4 integrin. In the present work, mRNA and protein levels of alpha6beta4 integrin were determined and its localisation in salivary glands evaluated in patients with Sjögren syndrome. METHODS: Salivary glands of 12 patients with Sjögren syndrome and 8 controls were studied. The mRNA and protein levels of alpha6beta4 were determined by semiquantitative reverse transcriptase (RT)-PCR and western blot analysis, respectively. The subcellular localisation of alpha6beta4 and laminin were evaluated by confocal microscopy. RESULTS: In patients, no significant differences in alpha6 and beta4 mRNA levels were detected. However, beta4 integrin protein levels were significantly lower, whereas, changes in alpha6, were highly variable. In controls, alpha6beta4 was detected in the basolateral and basal surface of serous and mucous acini, respectively. In patients, alterations in alpha6beta4 distribution were particularly dramatic for acini with strong basal lamina disorganisation. alpha6beta4 was also detected in the cytoplasm and lateral plasma membrane in serous and mucous acini. CONCLUSION: Mild alterations in the basal lamina correlated with lateral redistribution of alpha6beta4 integrin and the formation of new cell-cell adhesions that help maintain acinar organisation and promote cell survival. Conversely, in cases with severe basal lamina alterations, lateral alpha6beta4 redistribution was no longer sufficient to maintain acinar cell survival. Thus, maintenance of equilibrium between cell-cell and cell-basal lamina attachment is required to sustain gland cell survival.
18084707 A case of proteinase 3-antineutrophil cytoplasmic antibody-positive Sjögren's syndrome co 2007 A 65-year-old woman who had fever was admitted. Laboratory data showed renal tubular dysfunction, elevated C-reactive protein, soluble interleukin-2 receptor (sIL-2R), and IgG. Her blood showed proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) as well as antinuclear antibody and anti-Ro/SS-A antibody. Salivary gland and renal biopsy showed inflammatory infiltration of lymphocytes. A diagnosis of Sjögren's syndrome (SS) and interstitial nephritis was made. beta(2)-microglobulin, sIL-2R, IgG, and PR3-ANCA were decreased in response to medium-dose oral prednisolone. Antineutrophil cytoplasmic antibody could be a new marker for extraglandular features of SS. It would be beneficial for SS patients who have positive ANCA to investigate extraglandular lesions such as interstitial nephritis.
18050226 Increased apoptosis of peripheral blood lymphocytes and its association with interleukin-1 2007 Dec 15 OBJECTIVE: To determine spontaneous and activation-induced apoptosis of peripheral blood lymphocytes (PBLs) from patients with active untreated adult-onset Still's disease (AOSD) and to examine the role of interleukin-18 (IL-18) involved in the apoptosis related to this disease. METHODS: The percentages of spontaneous and IL-18-stimulated apoptotic lymphocytes in peripheral blood of 20 patients with active untreated AOSD, 20 with active untreated systemic lupus erythematosus (SLE), and 20 healthy controls were determined using annexin V/propidium iodide staining and flow cytometry. Serum IL-18 levels were measured using enzyme-linked immunosorbent assay. The transcripts of caspase 3 gene and apoptosis-regulating genes, including Fas, FasL, Bcl-2, and p53 in IL-18-treated peripheral blood mononuclear cells (PBMCs) from 8 AOSD patients, 4 SLE patients, and 4 healthy controls, were examined by real-time quantitative polymerase chain reaction. RESULTS: Significantly higher percentages of spontaneous and IL-18-stimulated apoptotic PBLs were found in patients with active untreated AOSD and those with active untreated SLE than in healthy controls. The percentages of spontaneous and IL-18-stimulated apoptotic lymphocytes correlated positively with clinical activity scores and serum IL-18 levels for AOSD patients and SLE patients. The percentages of spontaneous and activation-induced apoptotic PBLs significantly declined, paralleling clinical remission and the decrease in serum IL-18 levels after effective therapy in AOSD patients. Up-regulation of FasL and p53 transcripts was demonstrated in IL-18-treated PBMCs from AOSD patients and SLE patients in a dose-dependent manner. CONCLUSION: The increased apoptosis of PBLs from AOSD patients may be associated with the effect of IL-18 through up-regulation of FasL and p53 transcripts.
17665453 Modified aquaporin 5 expression and distribution in submandibular glands from NOD mice dis 2007 Aug OBJECTIVE: To investigate the expression and localization of aquaporin 5 (AQP5) in salivary glands and salivary gland function in the NOD mouse. METHODS: All experiments were performed using NOD and BALB/c mice (ages 8 weeks and 24 weeks). Real-time reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical analysis were used to study the expression and distribution of AQP5 in salivary glands. In addition, salivary gland function was determined. RESULTS: Compared with the levels in BALB/c mice, relative AQP5 messenger RNA levels were not significantly modified in the parotid glands from NOD mice of both ages but were significantly increased in the submandibular glands from NOD mice of both ages. Western blot analyses of both salivary gland membranes revealed that the level of AQP5 protein was increased in 24-week-old NOD mice. Important inflammatory infiltrates were observed in the submandibular glands, but not in the parotid glands, from 24-week-old NOD mice. The 8-week-old and 24-week-old BALB/c mice and the 8-week-old NOD mice showed AQP5 primarily at the apical membrane of the salivary gland acinus. In contrast, in acini from the submandibular glands (but not the parotid glands) from 24-week-old NOD mice, AQP5 staining was reduced at the apical membrane but was increased at the basal membrane. A moderately statistically significant decrease in pilocarpine-stimulated salivary flow was observed in 24-week-old NOD mice compared with that in age-matched BALB/c mice. CONCLUSION: Submandibular glands from 24-week-old NOD mice displayed inflammatory infiltrates, increased AQP5 protein expression, and impaired AQP5 distribution. However, the moderately statistically significant decrease in the salivary flow rate in these mice did not match the extent of AQP5 misdistribution.
17489060 Chronic hepatitis C infection and sicca syndrome: a clear association with HLA DQB1*02. 2007 Jun BACKGROUND: Hepatitis C virus infection is a major cause of nonA, nonB hepatitis worldwide. A high prevalence of immunological abnormalities has been shown to occur in patients with chronic hepatitis C virus infection. AIM: The aim of this study was to assess the development of sicca syndrome in a cohort of patients infected with a single strain of hepatitis C virus, namely genotype 1b, and correlate this with viral persistence and human leukocyte antigen type of the patients. METHODS: Ninety-five patients infected with the single strain hepatitis C virus were used in this study, 32 of whom were polymerase chain reaction-negative and 63 polymerase chain reaction-positive. Patient details were reviewed for symptoms consistent with sicca syndrome. Human leukocyte antigen class I (A, B and C) and class II (DRB and DQB1) typing was performed on all patients. Auto-antibodies were also measured. RESULTS: DQB1*02 was highly significantly associated with viral persistence (P<0.0001). Nineteen of 21 patients with sicca syndrome were hepatitis C virus-polymerase chain reaction-positive demonstrating a strong association with viral persistence and the development of the syndrome. Human leukocyte antigen DQB1*02 was significantly associated with the development of sicca syndrome, P=0.02. CONCLUSION: The development of autoimmune disease in patients with chronic hepatitis C virus infection depends on the interaction of multiple factors. This study suggests that important factors in this process are viral persistence and human leukocyte antigen type of the patients.
17208228 Lymphocytic infiltration and goblet cell marker alteration in the conjunctiva of the MRL/M 2007 Mar Sjögren's syndrome is an autoimmune disorder characterized by a progressive, immune-mediated destruction of mucosal tissues such as the lacrimal and salivary glands, leading to ocular and oral dryness. The MRL/MpJ-Fas(lpr) mouse is one of the animal models used to study this disease. However, little is known about the potential alterations in the conjunctiva in this murine model. The purpose of this study was to determine: (1) whether the conjunctiva is infiltrated by T lymphocytes, (2) characterize the type, amount and temporal sequence of the inflammatory infiltrates, and (3) investigate whether the amount of conjunctival goblet cells is altered in this murine model of Sjögren's syndrome. Female 4-, 9-, 13-, 16-, and 18-/20-wk-old MRL/MpJ-Fas(lpr) (lpr, diseased) and congenic MRL/MpJ (+/+, control) mice were used. Right eyes were either fixed, frozen, cryosectioned, and studied by immunofluorescence microscopy or the conjunctiva was removed, homogenized and analyzed by electrophoresis and Western blot analysis. The following antibodies were used: anti-CD3 (specific T lymphocyte marker), anti-cytokeratin 7 (CK-7), anti-PKD (formerly known as PKCmu, both markers of goblet cell bodies), anti-PGP 9.5 (pan-neuronal marker), anti-VIP and TH (markers for parasympathetic and sympathetic nerves, respectively), anti-adrenergic (alpha(1) and beta(1-3)) and muscarinic (M(1)-M(3)) receptor subtypes (markers for neurotransmitter receptors of the sympathetic and parasympathetic pathways, respectively). Left eyes were fixed, embedded, sectioned, and stained. Hematoxylin/eosin, Giemsa, or alcian blue/periodic acid Schiff's reagent were used to study lymphocyte infiltration; to determine the presence of eosinophils, neutrophils, and mast cells; and to count the number of goblet cells, respectively. By immunofluorescence microscopy, lymphocytes were detected in the conjunctiva of 9-wk-old lpr, but not +/+, mice. The lymphocytic infiltration became more extensive as the animals aged, with 16- and 18-/20-wk lpr mice appearing to have a greater lymphocytic infiltration than +/+ mice at the same age. By Western blot analysis, the amount of CD3 was enhanced in lpr compared to +/+ mice by the 16th wk, but not by the 9th wk. No major differences in the presence of eosinophils, neutrophils and degranulated mast cells between lpr and +/+ mice were observed. By light microscopy, a significant increase in goblet cell number was found in lpr mice compared to +/+ mice at 16 wks on. By Western blotting, the amount of CK-7 was significantly increased at 9 wks on and the amount of PKD was significantly increased at 16 wks. By immunofluorescence microscopy, there were no major differences in distribution of sympathetic and parasympathetic nerves present in the lpr conjunctiva compared to that of +/+ mice at any ages, although slight differences were observed with increased age. Muscarinic receptor expression was decreased, as less M(3) receptor subtype-associated immunofluorescence was detected in older lpr mice compared to +/+ mice and confirmed by Western blot analysis. No differences in the localization or the amount of alpha(1)- or beta(1-3)-adrenergic receptor immunodetection were observed between lpr and +/+ mice. We conclude that the conjunctiva is a target tissue in Sjögren's syndrome-related inflammation in this murine model.
16054750 Subacute aseptic meningitis as neurological manifestation of primary Sjögren's syndrome. 2006 Oct Sjögren's syndrome (SS) is an autoimmune disease characterized by inflammatory infiltration and secondary chronic dysfunction of exocrine glands. Systemic (extraglandular) manifestations of the disease occur in one-third of the patients, including a wide spectrum of peripheral and central neurological disorders. We report a case of subacute afebrile aseptic meningitis (AM) as neurological manifestation of primary SS. The neurological symptomatology presented gradual onset and progression, including diplopia, mild headache, pain and stiffness of the neck. The clinical examination pointed out xerostomia and xerophthalmia. Diagnosis of SS was confirmed by Schirmer's tear test and histopathology of the labial salivary glands. The neurological involvement was highlighted by gadolinium-enhanced magnetic resonance imaging of the brain which displayed an increased diffuse leptomeningeal enhancement. Cerebrospinal fluid (CSF) analysis showed moderate pleocytosis with prevalence of polymorphonuclear leukocytes and increased protein level but no evidence of Ig intrathecal synthesis. A cycle of intravenous steroid therapy led to a complete disappearance of the neurological symptomatology and to normalization of the CSF inflammatory pattern. Given the unusual presentation of this case of AM, which resembled the characteristics of a chronic meningitis rather than those of an acute form, in patients affected by SS we must stress the importance of cephalic symptoms such as headaches and cervical stiffness (even if mild and without fever) as possible signs of central neurological involvement of the disease.
18438817 Increased enthesopathy among Behçet's syndrome patients with acne and arthritis: an ultra 2008 May OBJECTIVE: Behçet's syndrome is characterized by clusters of disease expression, one of which is the coexistence of acne and arthritis. The aim of this study was to test the hypothesis that enthesopathy is increased in this cluster, having features reminiscent of acne-associated arthritis. METHODS: The study group comprised 35 patients with Behçet's syndrome who had acne and arthritis (BS-AA), 38 patients with Behçet's syndrome who did not have arthritis (BS-WA), 37 patients with ankylosing spondylitis (AS), 25 patients with rheumatoid arthritis (RA), and 25 healthy control subjects. Five entheseal sites (the superior and inferior poles of the patella, the tibial tuberosity, and the superior and inferior poles of the calcaneus) on both lower extremities were examined by 2 independent observers, using ultrasonography. A previously validated composite score was calculated for each patient. The numbers of entheseal sites giving a positive power Doppler signal in each group were also compared. RESULTS: Patients with AS had the highest enthesopathy score (mean +/- SD 4.1 +/- 2.4; F [4df] = 8.43, P < 0.001) followed by BS-AA patients (3.0 +/- 1.9; F [3df] = 3.63, P = 0.015). The mean +/- SD enthesopathy scores among the remaining 3 groups were similar (for BS-WA, 1.8 +/- 1.4; for RA, 2.2 +/- 1.6; for healthy controls, 2.0 +/- 1.5 [F (2df) = 0.65, P = 0.53]). Power Doppler scores were highest for the BS-AA group (mean +/- SD 3.0 +/- 1.5; F [4df] = 15.54, P < 0.001) followed by the AS group (2.7 +/- 1.8; F [3df] = 14.38, P < 0.001), the RA group (2.6 +/- 1.8; F [2df] = 13.88, P < 0.001), the BS-WA group (1.2 +/- 1.3; F [1df] = 4.48, P = 0.038), and the control group (0.5 +/- 1.1). There was 87% agreement between the 2 observers (kappa = 0.55, intraclass correlation coefficient 0.71). CONCLUSION: The increased presence of enthesopathy among BS-AA patients compared with that among BS-WA patients further supports the hypothesis that patients with Behçet's syndrome who also have arthritis and acne form a distinct cluster.
18601859 [Effects of Tongbi Mixture 2 on expressions of CD28 and CD152 and content of tumor necrosi 2008 Jul OBJECTIVE: To study the effects of Tongbi Mixture 2, a compound traditional Chinese herbal medicine for treating rheumatoid arthritis (RA), on immunoregulation of T lymphocytes in rats with collagen-induced arthritis (CIA). METHODS: Forty Wistar rats were randomly divided into normal control group, untreated group, Tongbi Mixture 2-treated group, methotrexate (MTX)-treated group and Tripterygium wilfordii polyglycoside (TWP)-treated group. Except for the rats of the normal control group (injection with normal saline), rats of the other four groups were subcutaneouly multipoint-injected with collagen protein II to induce CIA. The rats were treated with normal saline, Tongbi Mixture 2, MTX tablets and TWP tablets respectively for 36 days. The expressions of CD28 and CD152 were detected by flow cytometry, while the content of tumor necrosis factor-alpha (TNF-alpha) was analyzed by enzyme-linked immunosorbent assay. RESULTS: The expression of CD28 among the three drug treated groups had no statistical difference (P>0.05), while significantly higher than that of the normal control group (P<0.01) and lower than that of the untreated group (P<0.01). The expression of CD152 in the Tongbi Mixture 2 treated-group was lower than those of the MTX- and TWP-treated groups (P<0.05, P<0.01), but had no statistical difference as compared with the normal control group (P>0.05). There were no statistical differences in content of TNF-alpha between the drug treated groups and the normal control group (P>0.05), but the content of TNF-alpha of the drug treated groups was lower than that of the untreated group (P<0.05 or P<0.01). CONCLUSION: Tongbi Mixture 2 can inhibit T lymphocytes through down-regulating the expressions of CD28 and CD152 and the content of TNF-alpha, which may be the major mechanisms in treating RA.
18581212 Preparation of active proteins, vaccines and pharmaceuticals as fine powders using supercr 2008 Sep Supercritical or near-critical fluid processes for generating microparticles have enjoyed considerable attention in the past decade or so, with good success for substances soluble in supercritical fluids or organic solvents. In this review, we survey their application to the production of protein particles. A recently developed process known as CO2-assisted nebulization with a Bubble Dryer (CAN-BD) has been demonstrated to have broad applicability to small-molecule as well as macromolecule substances (including therapeutic proteins). The principles of CAN-BD are discussed as well as the stabilization, micronization and drying of a wide variety of materials. More detailed case studies are presented for three proteins, two of which are of therapeutic interest: anti-CD4 antibody (rheumatoid arthritis), alpha1-antitrypsin (cystic fibrosis and emphysema), and trypsinogen (a model enzyme). Dry powders were formed in which stability and activity are maintained and which are fine enough to be inhaled and reach the deep lung. Enhancement of apparent activity after CAN-BD processing was also observed in some formulation and processing conditions.
18300566 High mobility group box 1 in the pathogenesis of inflammatory and autoimmune diseases. 2008 Jan High mobility group box 1 is a nuclear protein participating in chromatin architecture and transcriptional regulation. When released from cells, HMGB1 can also act as a pro-inflammatory mediator or alarmin. Upon stimulation with lipopolysaccharides or tumor necrosis factor-alpha, HMGB1 is secreted from certain cells such as monocytes/macrophages and fosters inflammatory responses. In addition, HMGB1 is passively released from necrotic cells and mediates inflammation and immune activation. In contrast, during apoptotic cell death, nuclear HMGB1 becomes tightly attached to hypo-acetylated chromatin and is not released into the extracellular milieu, thereby preventing an inflammatory response. There is accumulating evidence that extracellular HMGB1 contributes to the pathogenesis of many inflammatory diseases, including autoimmune diseases. Increased concentrations of HMGB1 have been detected in the synovial fluid of patients with rheumatoid arthritis. In animal models of RA, HMGB1 appears to be crucially involved in the pathogenesis of arthritis since neutralization of HMGB1 significantly ameliorates the disease. Also, in the serum and plasma of patients with systemic lupus erythematosus we detected substantial amounts of HMGB1, which may contribute to the disease process. However, investigations of blood concentrations of HMGB1 and its relevance in human diseases are hindered by the lack of reliable routine test systems.
17347265 The emergence of proteinase-activated receptor-2 as a novel target for the treatment of in 2007 May 15 The signalling molecules that are involved in inflammatory pathways are now thought to play a part in many disorders of the central nervous system (CNS). In common with peripheral chronic inflammatory diseases such a rheumatoid arthritis and ulcerative colitis, evidence now exists for the involvement of inflammatory cytokines, for example tumour necrosis factor (TNF) and interleukins (IL), in neurological disorders. A common factor observed with the up-regulation of these cytokines in peripheral inflammatory diseases, is the increased expression of the proteinase-activated receptor (PAR) subtype PAR-2. Indeed, recent evidence suggests that targeting PAR-2 helps reduce joint swelling observed in animal models of arthritis. So could targeting this receptor prove to be useful in treating those CNS disorders where inflammatory processes are thought to play an intrinsic role? The aim of this review is to summarize the emerging data regarding the role of PAR-2 in neuroinflammation and ischaemic injury and discuss its potential as an exciting new target for the prevention and/or treatment of CNS disorders.
19016524 APRIL (TNFSF13) regulates collagen-induced arthritis, IL-17 production and Th2 response. 2008 Dec A proliferation-inducing ligand (APRIL or TNFSF13) shares receptors with B-cell activation factor of the TNF family (BAFF) on B and T cells. Although much is known about the function of APRIL in B cells, its role in T cells remains unclear. Blocking both BAFF and APRIL suggested that BAFF and/or APRIL contributed to collagen-induced arthritis (CIA); however, the role of APRIL alone in CIA remained unresolved. We show here that, in vitro, our newly generated APRIL(-/-) mice exhibited increased T-cell proliferation, enhanced Th2 cytokine production under non-polarizing conditions, and augmented IL-13 and IL-17 production under Th2 polarizing conditions. Upon immunization with OVA and aluminum potassium sulfate, APRIL(-/-) mice responded with an increased antigen-specific IgG1 response. We also show that in APRIL(-/-) mice, the incidence of CIA was significantly reduced compared with WT mice in parallel with diminished levels of antigen-specific IgG2a autoantibody and IL-17 production. Our data indicate that APRIL plays an important role in the regulation of cytokine production and that APRIL-triggered signals contribute to arthritis. Blockade of APRIL thus may be a valuable adjunct in the treatment of rheumatoid arthritis.