Sjögren-Larsson syndrome(SLS) is a rare hereditable disease characterized by congenital ichthyosis, spastic diplegia and mental retardation. Along with the typical triad of symptoms, many patients with this disease have short stature, kyphosis and glistening dots in the retina of the eye. The pathogenesism is unknown but recent studies suggest that SLS might be, at least in part, a disorder of fatty acid metabolism. We describe a patient with a pathognomonic finding in the fundus and with the classic features of SLS.
Cerebral Palsy ; Humans ; Ichthyosis ; Intellectual Disability ; Kyphosis ; Metabolism ; Retina ; Sjogren-Larsson Syndrome*

Biomarkers ; Humans ; Idiopathic Pulmonary Fibrosis/genetics* ; MicroRNAs/metabolism* ; Sjogren's Syndrome/genetics*

OBJECTIVETo study the variations of protein concentration in saliva stimulated and its effect on clinical diagnosis.

METHODSThe saliva from 33 normal controls and 73 patients with Sjögren syndrome (SS) who were stimulated with acid and not were collected. The concentration of beta 2 microglobulin (beta 2-mG), secretory immunoglobulin A (SIgA), and pH were measured by Radioimmunoassay, Rate Nephelometry and pH Detection Paper, respectively. SPSS 10.0 was used to determine the mean statistical differences among these groups.

RESULTSIn patients with SS, the concentration of beta 2-mG in saliva stimulated with Vc was significantly lower compared with that in saliva not stimulated (P < 0.01); In saliva stimulated with Vc, the concentration of beta 2-mG in patients with SS was higher than that in normal controls (P < 0.05). In normal controls, compared with that in saliva not stimulated, flow rate in saliva stimulated with 3% acetic acid and Vc was significantly higher (P < 0.01) and pH, concentration of beta 2-mG and SIgA were significantly lower (P < 0.01 and P < 0.05 respectively); there was a significant difference of flow rate, beta 2-mG, SIgA and pH in saliva between the subjects stimulated with 3% acetic acid and with Vc (P < 0.01).

CONCLUSIONSThe reason for the decrease of protein concentration in saliva stimulated may be the increase of flow rate caused by the decrease of pH or the decrease of pH itself. Protein detection of saliva stimulated in patients with SS is helpful in diagnosis, but the criterion is different between the saliva stimulated and not stimulated.

Adult ; Female ; Humans ; Hydrogen-Ion Concentration ; Immunoglobulin A, Secretory ; metabolism ; Male ; Saliva ; metabolism ; secretion ; Salivary Proteins and Peptides ; metabolism ; Sjogren's Syndrome ; diagnosis ; metabolism ; beta 2-Microglobulin ; metabolism

Biopsy ; Female ; Glomerular Basement Membrane ; metabolism ; Hashimoto Disease ; metabolism ; pathology ; Humans ; Kidney Diseases ; metabolism ; pathology ; Middle Aged ; Proteinuria ; metabolism ; pathology ; Sjogren's Syndrome ; metabolism ; pathology

OBJECTIVETo investigate the expression of proteasome immunosubunit low molecular weight polypeptide (LMP)2 and LMP7 in labial glands of patients with primary Sjogren's syndrome patients, and thus explore their role in the diagnosis, differential diagnosis and pathogenesis of primary Sjogren's syndrome (pSS).

METHODSLabial specimens were collected from 40 patients with pSS, 15 patients with connective tissue diseases other than pSS, and 9 healthy controls. The expressions of LMP2 and LMP7 in labial specimens were determined using immunohistochemical approaches and analyzed using semi-quantitative methods. The positive rate of acinar was calculated. After the square arcsine transformation of data, the differences of the positive rate in acinar between LMP2 and LMP7 were compared among three groups. Spearman's rank correlation coefficient was used for analyzing the correlation of clinical manifestations with LMP2 and LMP7 expressions.

RESULTSThe expressions of LMP2 and LMP7 within the acinar and ductal epithelial cells were confirmed. Although the LMP2 expression in labial specimens was not significantly different among three groups(P=0.369), the expression of LMP7 was significantly higher in pSS patients compared with patients with connective tissue disease and healthy controls (P<0.01). Only in pSS group, LMP7 was found to be with higher positive rate in acinar than LMP2 (P<0.01). No significant correlation was found between LMP2/LMP7 and clinical manifestations (P>0.05).

CONCLUSIONIn patients with pSS, the expression of LMP7 (but not LMP2) is up-regulated in labial gland, indicating these two proteins have different genetic regulation mechanisms.

Adult ; Cysteine Endopeptidases ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Proteasome Endopeptidase Complex ; metabolism ; Salivary Glands, Minor ; metabolism ; Sjogren's Syndrome ; diagnosis ; metabolism

Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder with worldwide incidence of 0.4 per 100,000 people. It is characterized by the triad of congenital ichthyosis, spastic diplegia or quadriplegia, and mental retardation. Herein we report a 2-year-old male child with SLS, asthma, and recurrent pneumonia. SLS was confirmed by a molecular genetics study that revealed a deletion mutation in the ALDH3A2 gene. An ALDH3A2 gene mutation results in dysfunction of the microsomal enzyme fatty aldehyde dehydrogenase and impaired metabolism and accumulation of leukotriene B4, which is a key molecule and a pro-inflammatory mediator in developing allergic diseases, especially asthma. An increased level of leukotriene B4 has been reported in SLS patients. As far as we are aware, this is the first report of SLS associated with asthma and recurrent pneumonia. In conclusion, pediatricians should be aware of and evaluate patients with SLS for possible associated asthma and allergic disorders.
Aldehyde Dehydrogenase ; Asthma* ; Cerebral Palsy ; Child ; Child, Preschool ; Humans ; Ichthyosis ; Incidence ; Intellectual Disability ; Leukotriene B4 ; Male ; Metabolism ; Molecular Biology ; Neurocutaneous Syndromes ; Pneumonia* ; Quadriplegia ; Sequence Deletion ; Sjogren-Larsson Syndrome*

OBJECTIVETo investigate the Raman spectral characteristics of the pathological lip minor salivary glands affected in primary Sjögren's syndrome.

METHODSThirty pathological samples and 30 normal samples were collected in this study. The samples were examined by Raman microscope.Support vector machine(SVM) was employed to analyze the data and establish the classification model.

RESULTSThe spectra of pathological tissues was different from the controls in proteins, nucleic acids, lipids and glycogen skeleton. The sensitivity, specificity and accuracy of the model established by SVM on the training sets were all 92.0% (92/100), but the sensitivity, specificity and accuracy of the model established by SVM on the testing sets were 69.2% (37/53), 100.0% (37/37) and 82.0% (73/89) respectively.

CONCLUSIONSThere was significant difference in Raman spectra between the pathological and normal lip salivary glands, and the classification model established by SVM could discriminate the pathological glands from the normal ones.

Female ; Glycogen ; metabolism ; Humans ; Keratins ; metabolism ; Lip ; metabolism ; pathology ; Lipids ; analysis ; Male ; Middle Aged ; Nucleic Acids ; metabolism ; Salivary Glands, Minor ; metabolism ; pathology ; Sjogren's Syndrome ; diagnosis ; metabolism ; pathology ; Spectrum Analysis, Raman ; methods

OBJECTIVETo investigate whether interferon-inducible protein 10 (IP-10) is involved in the inflammatory process of the labial gland of patients with Sjogren's Syndrome (SS).

METHODSForty-nine patients performed labial gland biopsy, the number of lymphocytes in the biopsy tissues was calculated and the IP-10 was detected by the methods as following: 39 biopsied labial tissues were examined by RT-PCR, among them, 21 were from primary SS, 5 from secondary SS and 13 from other diseases. With RT-PCR, the IP-10 and beta-actin were co-amplified with specific primers. The gel-fractioned and ethidium bromide amplification products were then analyzed by densitometry. The expression of IP-10 was semi-quantificated by IP-10/beta-actin ratio. Twenty-one samples were examined by immunohistochemistry with specific goat anti-IP-10 antibody, 10 of them from primary SS, 3 from secondary SS, 8 from other diseases. 11 out of 21 samples were examined by both RT-PCR and immunohistochemistry.

RESULTSThe expression of IP-10 mRNA was significantly up-regulated in labial glands of patients with SS compared with other diseases (IP-10/beta-actin ratio was 0.329 +/- 0.157 vs 0.099 +/- 0.059, P < 0.01). The number of lymphocyte infiltration foci in labial glands of patients with SS correlated to the IP-10/beta-actin ratio (r = 0.657, P < 0.05). Ductal epithelial cells and some of the infiltrating lymphocytes were stained by anti-IP-10 antibody by immunohistochemistry in 8 of the primary SS (8/10), all of the secondary SS (3/3) and one with primary biliary sclerosis (1/8). The expression of IP-10 protein detected by immunohistochemistry was consistent with that of mRNA detected by RT-PCR.

CONCLUSIONSIP-10 is abnormally highly expressed in the labial glands of patients with SS and positively relates to the lymphocyte infiltration. It thus suggests chemokine IP-10 may be one of the important molecules attracting the lymphocytes to the minor salivary glands to form the lymphocytic foci of Sjogren's Syndrome.

Adult ; Chemokine CXCL10 ; Chemokines, CXC ; biosynthesis ; genetics ; Epithelial Cells ; metabolism ; Female ; Humans ; Immunohistochemistry ; Lip ; metabolism ; Male ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Salivary Glands, Minor ; metabolism ; Sjogren's Syndrome ; metabolism ; Up-Regulation

BACKGROUND: Sjögren's syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. The treatment is still challenging. This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth (SHED-exos) in sialadenitis caused by SS. METHODS: SHED-exos were administered to the submandibular glands (SMGs) of 14-week-old non-obese diabetic (NOD) mice, an animal model of the clinical phase of SS, by local injection or intraductal infusion. The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice. Protein expression was examined by western blot analysis. Exosomal microRNA (miRNAs) were identified by microarray analysis. Paracellular permeability was evaluated by transepithelial electrical resistance measurement. RESULTS: SHED-exos were injected into the SMG of NOD mice and increased saliva secretion. The injected SHED-exos were taken up by glandular epithelial cells, and further increased paracellular permeability mediated by zonula occluden-1 (ZO-1). A total of 180 exosomal miRNAs were identified from SHED-exos, and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway might play an important role. SHED-exos treatment down-regulated phospho-Akt (p-Akt)/Akt, phospho-glycogen synthase kinase 3β (p-GSK-3β)/GSK-3β, and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells. Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1, a PI3K agonist. Slug bound to the ZO-1 promoter and suppressed its expression. For safer and more effective clinical application, SHED-exos were intraductally infused into the SMGs of NOD mice, and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and Slug and increased ZO-1 expression. CONCLUSION Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3β/Slug pathway-mediated ZO-1 expression.
Mice ; Animals ; Humans ; Sjogren's Syndrome/therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Tight Junctions/metabolism* ; Glycogen Synthase Kinase 3 beta ; Mice, Inbred NOD ; Phosphatidylinositol 3-Kinases/metabolism* ; Exosomes/metabolism* ; Xerostomia ; Phosphatidylinositol 3-Kinase ; MicroRNAs/genetics*

OBJECTIVETo explore the molecular mechanism of exocrine immune inflammatory injury of Sjögren's Syndrome and the intervention of Banxia Qinlian Decoction (BQD).

METHODSTotally 18 female NOD mice were randomly divided into the model group, the positive drug group, and the BQD group, 6 in each group. Six female BALB/c mice were recruited as a blank control group. Mice in the blank control group and the model group were gavaged with deionized water at the daily dose of 0.1 mL/10 g body weight. Tripterygium Tablet was administered by gastrogavage to mice in the positive group at the daily dose of 10 mg/kg. BQD was administered by gastrogavage to mice in the BQD group at the daily dose of 60 g crude drugs/kg. After 12 weeks of medication, mice were sacrificed. Their eyeballs were excised and blood collected. Tissues of bilateral parotids and submandibular glands were kept. mRNA transcriptional levels of IL-17, IL-6, type 3 muscarinic acetylcholine receptors (M3R), aquaporin protein-5 (AQP5) were detected by RT-PCR. Expression levels of M3R and AQP5 protein were detected by Western blot. Protein expression levels of IL-17 and IL-6 were detected by ELISA.

RESULTSCompared with the normal group, mRNA transcriptional levels and protein expression levels of IL-17, IL-6, M3R, and AQP5 were significantly up-regulated in the model group (P < 0.01). Compared with the model group, mRNA transcriptional levels and protein expression levels of IL-17, IL-6, M3R, and AQP5 were significantly down-regulated in the positive drug group and the BQD group with statistical difference (P < 0.01, P < 0.05). Compared with the BQD group, mRNA-transcriptional levels of IL-17, IL-6, and M3R, as well as M3R and AQP5 protein expression levels were significantly down-regulated in the positive drug group (all P < 0.01).

CONCLUSIONThe molecular mechanism of BQD in inhibiting SS exocrine neurotoxic injury might be possibly related to regulating Th17/IL-17 immune inflammatory way.

Animals ; Aquaporin 5 ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Interleukin-17 ; metabolism ; Interleukin-6 ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Sjogren's Syndrome ; drug therapy ; immunology ; Submandibular Gland ; Th17 Cells ; Up-Regulation