Xerostomia Research Today is a free monthly online journal that collates and summarizes the latest research about Xerostomia, including details on dry mouth, treatment, causes, lack of saliva.

The fellowship of the RING: the RING-B-box linker region interacts with the RING in TRIM21/Ro52, contains a native autoantigenic epitope in Sjögren syndrome, and is an integral and conserved region in TRIM proteins.

Hennig J, Bresell A, Sandberg M, Hennig KD, Wahren-Herlenius M, Persson B, Sunnerhagen M

Molecular Biotechnology, IFM, Campus Valla, Linköping University, SE-581 83 Linköping, Sweden.

Ro52 is a major autoantigen that is targeted in the autoimmune disease Sjögren syndrome and belongs to the tripartite motif (TRIM) protein family. Disease-related antigenic epitopes are mainly found in the coiled-coil domain of Ro52, but one such epitope is located in the Zn(2+)-binding region, which comprises an N-terminal RING followed by a B-box, separated by a approximately 40-residue linker peptide. In the present study, we extend the structural, biophysical, and immunological knowledge of this RING-B-box linker (RBL) by employing an array of methods. Our bioinformatic investigations show that the RBL sequence motif is unique to TRIM proteins and can be classified into three distinct subtypes. The RBL regions of all three subtypes are as conserved as their known flanking domains, and all are predicted to comprise an amphipathic helix. This helix formation is confirmed by circular dichroism spectroscopy and is dependent on the presence of the RING. Immunological studies show that the RBL is part of a conformation-dependent epitope, and its antigenicity is likewise dependent on a structured RING domain. Recombinant Ro52 RING-RBL exists as a monomer in vitro, and binding of two Zn(2+) increases its stability. Regions stabilized by Zn(2+) binding are identified by limited proteolysis and matrix-assisted laser desorption/ionization mass spectrometry. Furthermore, the residues of the RING and linker that interact with each other are identified by analysis of protection patterns, which, together with bioinformatic and biophysical data, enabled us to propose a structural model of the RING-RBL based on modeling and docking experiments. Sequence similarities and evolutionary sequence patterns suggest that the results obtained from Ro52 are extendable to the entire TRIM protein family.

Published 10 March 2008 in J Mol Biol, 377(2): 431-49.
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Articles on Xerostomia published 29 February 2008:

Glandular function in Sjögren syndrome: assessment with dynamic contrast-enhanced MR imaging and tracer kinetic modeling--initial experience.   Radiology, 246(3): 845-53.

PURPOSE: To prospectively use dynamic contrast material-enhanced magnetic resonance (MR) imaging and a tracer kinetic model to compare parotid gland microvascular characteristics in patients who have Sjögren syndrome (SS) with those in healthy volunteers. MATERIALS AND METHODS: The local research ethics committee approved the study, and written informed consent was obtained from all participants. Twenty-one patients (19 women, two men; age range, 31-73 years) with a diagnosis of SS and 11 ... [Abstract] [Full-text]

Articles on Xerostomia published 18 January 2008:

B-cell activating factor of the tumour necrosis factor family expression in blood monocytes and T cells from patients with primary Sjögren's syndrome.   Scand J Immunol, 67(2): 185-92.

We investigated B-cell activating factor of the tumour necrosis factor family (BAFF) level in peripheral blood mononuclear cells (PBMCs), monocytes and T cells from patients with primary Sjögren's syndrome (pSS) and controls both ex vivo and in vitro after cytokine stimulation. PBMCs, monocytes and T cells were isolated from 15 patients with pSS and 17 controls. Cells were cultured alone or with interferon (IFN)alpha, IFNgamma and interleukin 10 (IL-10). T cells were stimulated with ... [Abstract] [Full-text]

Articles on Xerostomia published 13 December 2007:

Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjögren syndrome: a randomised controlled trial.   Ann Rheum Dis, 67(1): 91-7.

OBJECTIVE: Dehydroepiandrosterone (DHEA) administration has been reported to improve fatigue, psychological distress, and physical disability. These are common features of primary Sjögren syndrome (pSS). We investigated the effects of DHEA administration on fatigue, well-being, and functioning in women with pSS. METHODS: In a double-blind, randomised placebo-controlled clinical trial, 60 female patients with pSS received 200 mg oral DHEA or placebo. Primary outcome measures were general ... [Abstract] [Full-text]

Articles on Xerostomia published 23 October 2007:

Primary lymphoma of the subglottic airway in a patient with Sjogren's syndrome mimicking high laryngotracheal stenosis.   Ann Thorac Surg, 84(5): 1756-8.

Primary B cell lymphoma of the central airways is a rare tumor. This report describes a case of primary B cell lymphoma of the subglottic airway in a patient with Sjogren's syndrome, which resembled a benign, cicatricial subglottic stenosis. Successful management was achieved using surgical resection with laryngotracheal reconstruction. [Abstract] [Full-text]

Articles on Xerostomia published 10 October 2007:

Parotid gland involvement, the presenting sign of high grade non-Hodgkin lymphoma in two patients with Gaucher disease and sicca syndrome.   J Inherit Metab Dis, 30(5): 825.

Increased risk of haematological malignancies has been described in Gaucher disease patients; however, high-grade lymphoma has been rarely observed. We report two patients with Gaucher disease and sicca syndrome diagnosed with aggressive lymphoma involving the parotid gland. A 29-year-old woman with Gaucher disease developed tumour of the left parotid gland. She reported chronic arthralgias, xerostomia and xerophthalmia. Parotid gland biopsy disclosed diffuse large B-cell lymphoma. No ... [Abstract] [Full-text]

Articles on Xerostomia published 3 October 2007:

A child with primary Sjögren syndrome and a review of the literature.   Clin Pediatr (Phila), 46(8): 738-42.

Primary Sjögren syndrome (pSS) is an uncommon disease in childhood. Childhood pSS might have different clinical manifestations than adult pSS. We describe a 13-year-old girl with multiple episodes of bilateral parotid swelling lasting 2 years. Her history included severe arthralgia, local edema, and purpura episodes since 9 years of age. During her 3-week hospitalization, 2 episodes of parotid swelling occurred, which both resolved in 48 hours. Ultrasonography and magnetic resonance images of ... [Abstract] [Full-text]

Articles on Xerostomia published 13 September 2007:

Fcgamma receptors mediate internalization of anti-Ro and anti-La autoantibodies from Sjögren's syndrome and apoptosis in human salivary gland cell line A-253.   J Oral Pathol Med, 36(9): 511-23.

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 ... [Abstract] [Full-text]

Articles on Xerostomia published 11 September 2007:

Elevated Th1/Th2 cell ratios in a pregnant woman with a history of RSA, secondary Sjögren's syndrome and rheumatoid arthritis complicated with one fetal demise of twin pregnancy.   Am J Reprod Immunol, 58(4): 325-9.

PROBLEM: Elevated Th1/Th2 cytokine producing CD3(+)/CD4(+) cell ratios were reported in women with a history of recurrent spontaneous abortion (RSA) and multiple implantation failures. We report, significantly elevated Th1/Th2 cell ratios were noticed in a pregnant woman with twin pregnancies complicated with one fetal demise, who had a history of RSA, secondary Sjögren's syndrome (SS), and rheumatoid arthritis. METHOD OF STUDY: Case report. RESULTS: Peripheral blood Th1/Th2 cell ratios were ... [Abstract] [Full-text]

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