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ID PMID Title PublicationDate abstract
18477009 Hydroxychloroquine-associated, photo-induced toxic epidermal necrolysis. 2008 Aug A patient developed toxic epidermal necrolysis (TEN), which was triggered by sun exposure while the patient was on long-term hydroxychloroquine. Phototoxic and photoallergic reactions are known to occur with hydroxychloroquine, but, to our knowledge, this is the first reported case of photo-induced TEN associated with the drug.
17713716 Autoantibodies to novel membrane and cytosolic antigens of the lachrymal gland in primary 2008 Feb Sjögren's syndrome (SS) is a prototypical systemic autoimmune disease, where autoimmune processes lead to the dysfunction of the exocrine glands. The key feature of the disease is autoimmune exocrinopathy, causing reduced tear secretion and subsequent keratoconjunctivitis sicca (KCS). The aim of this study was to investigate the connection between the presence of autoantibodies to lachrymal gland antigens and the reduced tear production in patients with primary SS. Ninety-nine patients, 90 women and 9 men, were investigated in the study. Twenty healthy young women served as controls. Enzyme-linked immunosorbent assay (ELISA) and Western blotting were applied to detect autoantibodies to antigen fractions prepared from the human lachrymal gland membrane and cytosolic fractions. Autoantibodies of the IgG, IgA and IgM isotypes to the lachrymal membrane and cytosolic fractions were detected in about one third (27%) of the patients with primary SS. IgA antobodies to the membrane and cytosolic fractions occurred most frequently in SS patients. A significant difference was found in the presence of IgA antibodies to the membrane lachrymal fraction between patients and controls given in ELISA indices (1.23 +/- 0.3 vs 1 +/- 0.19, p < 0.001). IgG, IgA, and IgM isotypes of autoantibodies directed to the membrane lachrymal fraction of 200-180, 120-116, 80-70, 58, 50, 48.5, 40 and 28.8 kDa were also identified in patients. Membrane IgG antibody levels showed a positive correlation (R = 0.998; p = 0.045) with the clinical loss of secretory function (Schirmer's test values). Positive correlation was found between membrane IgM and anti-SS-A levels (R = 0.962; p = 0.038) and also between cytosolic IgM antibodies and anti-SS-A levels (R = 0.982; p = 0.018). IgG, IgA and IgM types of autoantibodies may play a role in the development of the impaired lachrymal secretion and therefore may be involved in the pathogenesis of KCS.
17713098 Comparison of human papillomavirus testing and cervical cytology with colposcopic examinat 2007 OBJECTIVE: The purpose of this study was to evaluate women with Sjögren Syndrome by using cervical cytology, colposcopic examination and HPV-DNA testing and to compare these findings with those obtained from the control group. METHOD: A total of 100 women, who were referred to Ege University, School of Medicine, Department of Obstetrics and Gynecology for cervical cytological screening between September 2004 and March 2005 and 33 of whom had Sjögren syndrome were included in this study. The patients were informed and subjected to cervical cytology, colposcopic examination and HPV-DNA testing. Colposcopic biopsy and endocervical canal curettage were carried out in cases of suspicious colposcopic examination and cytological findings. The findings obtained from 33 women with Sjögren syndrome and 67 subjects in the control group were compared. RESULTS: Normal cervical cytology was detected in five women (5.7%), while suspicious cervical cytology was reported in 62 women (92.5%) in the control group. The prevalence of normal cytology in patients with Sjögren syndrome was 93.9% (n = 31), where 6.1% (n = 2) of the women had suspicious cervical cytology findings. HPV-DNA findings were negative in 66 women (98.5%) in the control group, where the test result of one women (1.5%) was positive. HPV-DNA findings of patients with Sjögren syndrome were positive in one women (3%) and negative in 32 (97%). Colposcopic findings were normal in 63 women (94%) in the control group, where abnormal colposcopic findings were observed in four women (6%). Normal colposcopic findings were observed in 32 women (97%) with Sjögren syndrome, while pathological findings were recorded in one woman (3%). Suspicious cervical cytology, positive findings at colposcopic examination and biopsy and positive HPV-DNA tests were observed together in only one 40-year-old woman who was diagnosed with Sjögren syndrome for a period of four years. Prevalence of dyspareunia and vaginal dryness (atrophic vaginitis) symptoms were observed in Sjögren syndrome and control groups as 36.3% and 22.3%, respectively. CONCLUSION: No significant differences were observed between Sjögren syndrome and the control group who were evaluated by using cervical cytology, colposcopic examination and HPV-DNA tests. A higher prevalence of dyspareunia and vaginal dryness were observed in patients with Sjögren syndrome, yet this difference was not considered as significant with respect to either colposcopic or histopathological findings.
17562045 Family history of lymphoma and risk for solid tumors in patients with Sjogren's syndrome. 2007 Nov It has been recognized that primary Sjogren's syndrome predisposes to the development of lymphoproliferative disorders. However, it is so far uncertain whether these patients are at an increased risk for solid tumors. Herein we report two cases of primary Sjogren's syndrome complicated by breast and lung cancer and who have a strong family history for lymphoproliferative diseases.
17396337 [Dysthyroidism and connective pathology]. 2006 Dec AIM: The aim of the study is to evaluate the degree of the relationship between dysthyroidism and connective pathology, both autoimmune diseases, presenting, sometimes, an early common symptom: the Raynaud phenomenon. METHOD: We studied 30 patients subdivided as follows: 18 affected by mixed connective pathology, 6 by scleroderma, 2 by CREST, 4 by scleroderma and Sjogren syndrome. We focused our attention on the chronology and the duration of the diagnosis, correlated to the laboratory parameters and the hypothesis of the pathogenetic pathway. RESULTS: 36.6% were positive to both the pathologies. One of the 11 patients resulted positive to hyperthyroidism and mixed connective, 10 patients resulted positive to hyperthyroidism subdivided in: 6 affected by sclerodermia and by 4 sclerodermia and S. of Sjogren. All the patients were positive to ANA without correlation between those values and the microsomal or antithyreoglobulin antibodies: the last two were present in 33%. The laboratory parameters indicating the inflammatory state were in the normal range, a light hypercholesterolemia was found in all patients. CONCLUSION: There is a suggestive relationship between the connective pathology and dysthyroidism,therefore it can be useful to evaluate always the association of both pathologies for the future identification of the immunogenetic alteration factors, the evaluation of the composition and the turnover of the collagen, subdividing the patients in relation to the clinical and the laboratory parameters, follow up to middle and long term.
16941199 Central nervous system lymphoma in a patient with Sjogren's syndrome and autoimmune thyroi 2007 Aug We present a case of central nervous system (CNS) lymphoma in a patient with Sjogren's syndrome (SS) and autoimmune thyroiditis (Hashimoto's thyroiditis) overlap. A 60-year-old woman, who had the diagnosis of SS for 16 years, had been admitted for visual loss, fever, weight and appetite loss for 3 months. Cranial magnetic resonance imaging was in accordance with CNS lymphoma, and biopsy from right parietal region showed diffuse large B-cell lymphoma of the CNS. This is the first report of diffuse large B-cell lymphoma of the CNS in SS and autoimmune thyroiditis (Hashimoto's thyroiditis) overlap.
16749244 CLS meets the aquaporin family: clinical cases involving aquaporin systems. 2006 Spring Virtually all human cells incorporate aquaporins, or water channel proteins, into their cell membrane. Indeed, many cells produce several aquaporins, each adapted for a specific physiologic function. Thus, it is not surprising that aquaporin malfunctions are associated with numerous important clinical conditions. This article describes the clinical aspects of malfunctions in aquaporins or their regulation. Although water can diffuse across biological membranes (osmosis) without the aid of a transport system, researchers had predicted for decades that rapid reabsorption by renal tubule cells must be aided by a channel or pore. Yet, not until the 1990s were the first members of the aquaporin (AQP) family identified. Led by Dr. Peter Agre, recipient of the 2003 Nobel Prize in Chemistry, researchers have since amassed an astounding amount of information about AQPs and their function. For example, the flow rate of water through AQP1 is an extraordinary three billion water molecules per second per aquaporin channel, while a relative trickle of water crosses the hydrophobic lipid bilayer of cell membranes devoid of AQPs. Our understanding of renal physiology and pathophysiology has advanced greatly as we account for the subtle implications of various AQP systems. For example, nephrogenic diabetes insipidus (NDI), the inability to produce concentrated urine, can result from several different malfunctions in the hormonally controlled AQP2 system. The list of diseases known to involve AQPs now includes: early onset of cataracts, Sjogren's syndrome, cerebral and pulmonary edemas, cirrhotic liver development of ascites, and congestive heart failure (CHF).
18560967 Mucosa-associated lymphoid tissue lymphoma of the thymus associated with Sjögren's syndro 2008 A 68-year-old Japanese man with Sjögren's syndrome was pointed out to have a nodular shadow in the anterior mediastinum. The tumor was resected under video-assisted thoracoscopy and it was pathologically diagnosed to be thymic mucosa-associated lymphoid tissue (MALT) lymphoma. There has been no recurrence for 17 months after surgery. Mucosa-associated lymphoid tissue lymphoma of the thymus is rare, and its pathological diagnosis requires sufficient knowledge and experience. Since thymic MALT lymphoma is distinct from MALT lymphoma of other sites in several ways, including gene abnormalities and geographic distribution, an alternative oncogenic pathway and the influence of racial and/or environmental factors must be considered to be involved. However, since the number of reported thymic MALT lymphomas is limited, these issues are still unclear. The accumulation of further similar cases will help to elucidate various issues concerning thymic MALT lymphoma associated with Sjögren's syndrome.
18184611 MUC19 expression in human ocular surface and lacrimal gland and its alteration in Sjögren 2008 Feb This study investigated the expression of MUC19, a newly discovered gel-forming mucin gene, in normal human lacrimal functional unit components and its alteration in Sjögren syndrome patients. Real-time PCR and immunohistochemistry were performed to determine the expression of MUC19 and MUC5AC in human cornea, conjunctiva, and lacrimal gland tissues. Conjunctival impression cytology specimens were collected from normal control subjects and Sjögren syndrome patients for Real-time PCR, PAS staining, and immunohistochemistry assays. In addition, conjunctiva biopsy specimens from both groups were examined for the expression differences of MUC19 and MUC5AC at both mRNA and protein level. The MUC19 mRNA was found to be present in cornea, conjunctiva and lacrimal gland tissues. The immunohistochemical staining of mucins showed that MUC19 was expressed in epithelial cells from corneal, conjunctival, and lacrimal gland tissues. In contrast, MUC5AC mRNA was only present in conjunctiva and lacrimal gland tissues, but not in cornea. Immunostaining demonstrates the co-staining of MUC19 and MUC5AC in conjunctival goblet cells. Consistent with the significant decrease of mucous secretion, both MUC19 and MUC5AC were decreased in conjunctiva of Sjögren syndrome patients compared to normal subjects. Considering the contribution of gel-forming mucins to the homeostasis of the ocular surface, the decreased expression of MUC19 and MUC5AC in Sjögren syndrome patients suggested that these mucins may be involved in the disruption of the ocular surface homeostasis in this disease.
17992593 Clinical, immunologic, and molecular factors predicting lymphoma development in Sjogren's 2007 Jun Among autoimmune diseases, Sjogren's syndrome (SS) displays the highest incidence of non-Hodgkin lymphoma (NHL) development with the salivary extranodal marginal zone B cell lymphomas being the most common type. The majority of SS-associated NHLs are characterized by localized stage, indolent clinical course, and recurrence in other extranodal sites. Although the transition from a chronic inflammatory condition to malignant lymphoma is a multistep process yet poorly understood, there is increasing evidence that chronic antigenic stimulation by an exoantigen or autoantigens plays an essential role in the development of SS associated lymphoproliferation. Additional molecular oncogenic events such as microsatellite instability, loss of the B cell cycle control, and the forced overproduction of specific B cell biologic stimulators seem to contribute to the emergence and progression of the malignant overgrowth. Among the clinical and serological parameters that have been associated with lymphoma development in SS patients, the presence of palpable purpura, low C4, and mixed monoclonal cryoglobulinemia constitute the main predictive markers, and patients displaying these risk factors should be monitored closely.
17850433 Fcgamma receptors mediate internalization of anti-Ro and anti-La autoantibodies from Sjög 2007 Oct BACKGROUND: The presence of serum anti-Ro and anti-La autoantibodies directed against the ribonucleoproteins Ro and La has been associated with Sjögren's syndrome (SS), an autoimmune rheumatic disease that targets salivary and lachrymal glands. There is increasing evidence of the direct involvement of autoantibodies in the pathogenesis of tissue injury and correlation of their presence with clinical manifestations in SS. The focus of this work was to explore the cellular apoptotic pathway triggered by binding and penetration of anti-Ro and anti-La autoantibodies in human salivary gland cell line A-253 and to identify the membrane receptors through which anti-Ro and anti-La could exert their effect. METHODS: Anti-Ro and anti-La autoantibodies were purified from IgG fractions, obtained from eleven healthy volunteers and patients with primary Sjögren's syndrome, using Sepharose 4B-Ro and Sepharose 4B-La affinity columns. Flow cytometry, RT-PCR, western blot and confocal microscopy analysis were used to visualize the FCgammaRI, FCgammaRII and FCgammaRIII receptors on the A-253 cell membrane. DNA laddering and western blot analysis of caspases activation were studied to evaluate in A-253 cells treated with anti-Ro and anti-La autoantibodies. RESULTS: The results yeilded the evidence of the presence of members of the Fcgamma receptors (FcgammaRs) family on the cell membrane of the human salivary gland cell line A-253. Furthermore, we demonstrated that, in the A-253 cell line, anti-Ro and anti-La autoantibodies can access the cells probably through Fcgamma receptors, and trigger apoptotis. CONCLUSIONS: We conclude that anti-Ro and anti-La autoantibodies have pathogenic effects that could depend on binding to Fcgamma receptors.
17302899 Expression of functional Toll-like receptors by salivary gland epithelial cells: increased 2007 Mar Toll-like receptors (TLR) play an essential role in the activation of both innate and adaptive immune responses. Salivary gland epithelial cells (SGEC) may participate in the development of glandular inflammatory reactions that characterize primary Sjögren's syndrome (pSS). In this study we sought to assess the expression and function of several TLR molecules in cultured non-neoplastic SGEC obtained from pSS patients and disease controls. Long-term cultured non-neoplastic SGEC derived from pSS patients (SS-SGEC) and disease controls (control-SGEC), as well as the monocytic cell line THP-1 (positive control cell line), were examined by reverse transcription-polymerase chain reaction (RT-PCR) analysis and quantitative real-time PCR for mRNA expression of TLR1, -2, -3 and -4 molecules. TLR function was assessed by the induction of the expression (flow cytometry) of the immunoregulatory molecules CD54/intercellular adhesion molecule-1 (ICAM-1), CD40, CD86/B7 x 2, major histocompatibility complex (MHC) class I and MHC class II following treatment with the TLR ligands: Staphylococcus aureus peptidoglycan (TLR2), the synthetic dsRNA analogue polyinosinic:cytidylic acid (TLR3) and Escherichia coli lipopolysaccharide (TLR4). SGEC were found to express functional TLR2, -3 and -4 molecules, as attested by dose-dependent up-regulation of surface ICAM-1, CD40 and MHC-I expression (as well as of reciprocal TLR mRNA) following treatment with the respective TLR-ligands. SS-SGEC lines displayed significantly higher constitutive expression of TLR1 (P=0 x 0027), TLR2 (P=0 x 01) and TLR4 (P=0 x 03) mRNA compared to control-SGEC. This study demonstrates that cultured SGEC express functional TLR molecules; the high constitutive TLR expression by SS-SGEC is probably suggestive of the intrinsic activation of epithelial cells in pSS and further supports the role of this type of tissue in pathogenesis of the disorder.
18383373 A B cell apotope of Ro 60 in systemic lupus erythematosus. 2008 Apr OBJECTIVE: Previous studies have attempted to segregate anti-60-kd Ro/SSA (anti-Ro 60) responses in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS) but have shown limited disease preference. The aim of the present study was to determine whether the presence of autoantibodies against an Ro 60 apotope (an epitope expressed on apoptotic cells) distinguishes anti-Ro 60 responses in SLE and primary SS. METHODS: Multiparameter flow cytometry was used to select early apoptotic cells and measure the simultaneous binding of annexin V, propidium iodide, and anti-Ro 60-positive IgG from SLE patients (n=21) and patients with primary SS (n=19). The specificity of the Ro 60 apotope was determined by inhibition experiments with recombinant and native Ro 60. RESULTS: Autoantibodies against the Ro 60 apotope were prevalent in SLE patients (13 of 21, 62%) and were rarely observed in patients with primary SS (1 of 19, 5%) (P=0.0002). Further, within SLE patients, autoantibodies to the Ro 60 apotope strongly distinguished patients with anti-Ro 60 alone (12 of 13, 92%) from those with both anti-Ro 60 and anti-La (1 of 8, 13%) (P=0.0005). When we considered all patients with anti-Ro 60 alone, the presence of autoantibodies to the Ro 60 apotope had both high sensitivity (92.3%) and high specificity (85.7%) for SLE compared with primary SS (P=0.0012). The presence of autoantibodies to the Ro 60 apotope may therefore be of diagnostic value in patients with isolated anti-Ro 60 responses. CONCLUSION: The preferential targeting of an Ro 60 apotope exposed on early apoptotic cells in a subset of SLE patients implies disease-specific pathways for the induction of anti-Ro 60 autoimmunity.
18328155 Is the heart affected in primary Sjögren's syndrome? An echocardiographic study. 2008 Jan OBJECTIVE: To evaluate whether patients with primary Sjögren's syndrome without overt cardiac disease have echocardiographic abnormalities and their relation with clinical and laboratory data. METHODS: One hundred and seven consecutive patients with primary Sjögren's syndrome and 112 healthy controls, matched for age and gender, underwent complete echocardiographic study. RESULTS: Thirty-two patients had mitral valve regurgitation (p<0.001) whereas tricuspid and aortic valve regurgitation were, also, more frequent in the patient group (p=0.022 and p=0.007 respectively). In multivariate analyses, low C4 levels of complement and age were strong predictors of mitral valve regurgitation whereas age was predictor of aortic valve regurgitation. Tricuspid valve regurgitation was associated with pulmonary hypertension. Clinically silent pericardial effusion, found in 9 patients (p=0.008), was associated with cryoglobulinemia and primary biliary cirrhosis. Twenty-four patients had pulmonary hypertension (p<0.001) whereas hypocomplementemia and cryoglobulinemia were strong predictors of pulmonary artery systolic pressure. The analyses reveal that easy fatigability was associated with pulmonary hypertension and low C4 levels. The patients' left ventricular mass index differed significantly from the controls (108.9+/-17.21 gm(-2) vs. 85.8+/-6.73 gm(-2), p<0.001) and was associated with palpaple purpura and anti-Ro/SSA. From the diastolic function indices only the left ventricular isovolumic relaxation time differed significantly among patients and controls. CONCLUSION: Valvular regurgitation, pericardial effusion, pulmonary hypertension and increased left ventricular mass index occur with disproportionately high frequency in patients with primary Sjögren's syndrome and no clinically apparent heart disease. Thus echocardiographic studies may need to be performed in these patients especially when palpable purpura, antibody reactivity and low C4 levels are present.
17278022 CD40-CD40 ligand signal induces the intercellular adhesion molecule-1 expression through n 2007 The purpose of this study is to clarify signal transduction of expression of the intercellular adhesion molecule-1 (ICAM-1) via CD40-CD40 ligand in salivary glands of patients with Sjögren's syndrome (SS). We used cultured salivary gland epithelial cells (SG cells) from 15 SS patients and 8 controls obtained by labial minor salivary gland biopsy. First, ICAM-1 expression was determined with reverse transcriptase-polymerase chain reaction and flow cytometry in the presence or absence of soluble CD40L (sCD40L). Next, SG cells were transfected with plasmids of pGL1.3-Luc inserted with promoter region of ICAM-1, pGL1.3kB(-)-Luc mutated in nuclear factor kappa-B (NF-kappaB) binding site of pGL1.3-Luc and pNF-kappaB-Luc by lipofection method. Luciferase activity of the cells was measured in the presence or absence of sCD40L or sCD40L and an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC). Finally NF-kappaB family proteins of cell nuclear extracts were determined. ICAM-1 expression was significantly enhanced with sCD40L at the mRNA and protein level. Activity of pNF-kappaB-Luc and pGL1.3-Luc was significantly elevated by stimulation with sCD40L and suppressed by PDTC. NF-kappaB p50 protein level was elevated by stimulation with sCD40L and suppressed by PDTC. Our results suggest that sCD40L enhances the ICAM-1 expression by activation of NF-kappaB p50 in the SS SG cells.
16797160 Autoantibodies from Sjögren's syndrome induce activation of both the intrinsic and extrin 2006 Aug Sjögren's syndrome (SS) is an autoimmune rheumatic disease that targets salivary and lachrymal glands, characterized by a high concentration of serum autoantibodies directed against nuclear and cytoplasmic antigens. It is known that autoantibodies can enter viable cells and this phenomenon has functional consequences including activation of apoptotic process. The objective of this work was to explore whether autoantibodies contained in IgG purified from Sjögren sera trigger apoptotic process in an experimental model represented by the human salivary gland cell line A-253. To define if the intrinsic or extrinsic pathways are activated, we examined which caspases are critical for inducing cell death. The results have demonstrated that morphological changes and DNA laddering, consistent with apoptotic cell death, occurred in A-253 cells treated with IgG from Sjögren sera. Sjögren IgG induced cleavage and activation of the effector caspase-3 and degradation of the caspase-3 substrate poly(ADP-ribose)polymerase. Both the intrinsic and extrinsic apoptotic pathways were activated, since both caspase-8 and caspase-9 cleavages occurred. In conclusion, autoantibodies contained in IgG purified from Sjögren sera mediate apoptosis of the A-253 cell line in a caspase-dependent manner.
16572451 Antimuscarinic antibodies in primary Sjögren's syndrome reversibly inhibit the mechanism 2006 Apr OBJECTIVE: Sjögren's syndrome (SS) is an autoimmune condition affecting salivary glands, for which a clearly defined pathogenic autoantibody has yet to be identified. Autoantibodies that bind to the muscarinic M3 receptors (M3R), which regulate fluid secretion in salivary glands, have been proposed in this context. However, there are no previous data that directly show antisecretory activity. This study was undertaken to investigate and characterize the antisecretory activity of anti-M3R. METHODS: Microfluorimetric Ca2+ imaging and patch clamp electrophysiologic techniques were used to measure the secretagogue-evoked increase in [Ca2+]i and consequent activation of Ca2+-dependent ion channels in individual mouse and human submandibular acinar cells. Together, these techniques form a sensitive bioassay that was used to determine whether IgG isolated from patients with primary SS and from control subjects has antisecretory activity. RESULTS: IgG (2 mg/ml) from patients with primary SS reduced the carbachol-evoked increase in [Ca2+]i in both mouse and human acinar cells by approximately 50%. IgG from control subjects had no effect on the Ca2+ signal. Furthermore, the inhibitory action of primary SS patient IgG on the Ca2+ signal was acutely reversible. We repeated our observations using rabbit serum containing antibodies raised against the second extracellular loop of M3R and found an identical pattern of acutely reversible inhibition. Anti-M3R-positive serum had no effect on Ca2+-dependent ion channel activation evoked by the direct intracellular infusion of inositol 1,4,5-triphosphate. CONCLUSION: These observations show for the first time that IgG from patients with primary SS contains autoantibodies capable of damaging saliva production and contributing to xerostomia. The unusual but not unprecedented acute reversibility of the effects of anti-M3 autoantibodies is the subject of further research.
18718225 The role of radiology in the management of systemic sclerosis. 2008 Sep Systemic sclerosis is a multisystem connective tissue disorder. Radiology plays an integral part in its management, guiding the clinician concerning the onset and severity of visceral involvement. After skin involvement, the gastrointestinal tract is the most commonly affected system; contrast radiography and magnetic resonance imaging (MRI) play a role in diagnosis. Non-specific interstitial pneumonia is the most frequent respiratory disease and high-resolution computed tomography (CT) is the cornerstone of management. In common with other rheumatic disorders, the role of cardiac MRI is expanding. Radiography remains the main technique in the investigation of skeletal involvement, although MRI is useful as a problem-solving tool. Neurological involvement is increasingly recognized and the major role of radiology is the exclusion of coexistent pathology. We present a thorough review of the role of radiology in the management of systemic sclerosis.
18696337 Altered distribution of aquaporin 5 and its C-terminal binding protein in the lacrimal gla 2008 Aug PURPOSE: To investigate the distribution and expression of aquaporin 5 (AQP5) and its C-terminal binding protein in the apical membrane of the lacrimal glands (LGs) in a mouse model for Sjogren's syndrome (SS). METHODS: The LGs of NOD mice (mouse model for SS) and ICR mice (normal control) were homogenized and delivered into the affinity columns bound to synthetic AQP5 C-terminal peptide. The eluates were analyzed by electrophoresis and liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) techniques. RESULTS: AQP5 from the NOD mice exhibited the capacity to bind a 21-kDa protein that was lacking in the ICR mice. Instead, ICR mouse expressed a 17-kDa AQP5 binding protein that was absent in LGs of SS. LC-MS/MS analysis revealed these respective proteins to be major urinary protein 4 (MUP4) and prolactin-inducible protein (PIP). The treatment of ICR mice with antisense PIP oligonucleotides decreased immunostaining of AQP5 in the apical membrane. CONCLUSIONS: These observations suggest that the binding of PIP to the C-terminal portion of AQP5 may cause AQP5 to be transported to the apical membrane of LGs. Correction of the aberrant binding of PIP to the AQP5 C-terminus could normalize AQP5 trafficking to the apical membrane, leading to a treatment for patients with SS.
18558572 [Thrombotic thrombocytopenic purpura: a case report]. 2008 May We report a case of thrombotic thrombocytopenic purpura (TTP) in a 60 years-old woman with Sjogren's syndrome. Symptomatology on admission leads to evoke the diagnosis of TTP. Biological results allow to set the diagnosis. Actually, association of haemolytic anaemia, schizocytes and thrombocytopenia are in favour of TTP. Undetectable ADAMTS 13 activity (below 5%) confirms the diagnosis. In congenital TTP, plasma ADAMTS 13 is absent or severely reduced as a consequence of mutations in the two ADAMTS 13 gene. In acquired TTP, circulating antibodies inhibit plasma ADAMTS 13 activity. In those cases, further biological studies are needed to find a cause of TTP. Follow-up implies standard laboratory tests. Plasma exchanges are progressively tapered after normalization of platelets count.