Dataset Information

Brief Report: Patients With Primary Sjogren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity.

ABSTRACT: Autoantibodies reactive with Ro52 (tripartite motif-containing protein 21 [TRIM21]) are detected in 70% of patients with primary Sjögren's syndrome (SS). TRIM21 belongs to a 34-member C-IV family of TRIM proteins. Although autoantibodies against other TRIM proteins within the C-IV family have been detected in the sera of patients with primary SS, their clinical relevance remains unclear. This study was undertaken to investigate the frequency of anti-TRIM38 in patients with primary SS and evaluate its association with various clinical measures of the disease.Serum samples from patients with primary SS (n?=?235) and controls (n?=?50) were analyzed for reactivity with in vitro-transcribed and -translated (35) S-methionine-labeled TRIM38 protein. The associations of anti-TRIM38 with various laboratory and clinical measures of primary SS were evaluated. Reactivity of anti-TRIM38 with different structural domains of TRIM38 was analyzed. Affinity-purified anti-TRIM38 antibodies were used to immunoprecipitate TRIM21.TRIM38-reactive autoantibodies were detected in the sera of 24 of the 235 patients with primary SS and 2 of the 50 controls. Anti-TRIM38 positivity was significantly associated with the presence of anti-Ro60, anti-Ro52, anti-La, rheumatoid factor, and hypergammaglobulinemia. Clinically, anti-TRIM38 was associated with significantly higher ocular surface staining scores, lower Schirmer's test scores, and minor labial salivary gland biopsy focus scores of ?3.0. Anti-TRIM38 antibodies mainly recognized the cortactin-binding protein 2 (CortBP-2; amino acids 128-238) and the B30.2/SPRY (amino acids 268-465) domains on TRIM38. Affinity-purified antibodies to TRIM38-CortBP-2 and TRIM38-B30.2/SPRY domains reacted with TRIM21.Our data demonstrate that anti-TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease.

SUBMITTER: Wolska N

PROVIDER: S-EPMC4767665 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Brief Report: Patients With Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity.

Wolska Nina N Rybakowska Paulina P Rasmussen Astrid A Brown Michael M Montgomery Courtney C Klopocki Arkadiusz A Grundahl Kiely K Scofield Robert H RH Radfar Lida L Stone Donald U DU Anaya Juan M JM Ice John A JA Lessard Christopher J CJ Lewis David M DM Rhodus Nelson L NL Gopalakrishnan Rajaram R Huang Andrew J W AJ Hughes Pamela J PJ Rohrer Michael D MD Weisman Michael H MH Venuturupalli Swamy S Guthridge Joel M JM James Judith A JA Sivils Kathy L KL Bagavant Harini H Deshmukh Umesh S US

Arthritis & rheumatology (Hoboken, N.J.) 20160301 3

<h4>Objective</h4>Autoantibodies reactive with Ro52 (tripartite motif-containing protein 21 [TRIM21]) are detected in 70% of patients with primary Sjögren's syndrome (SS). TRIM21 belongs to a 34-member C-IV family of TRIM proteins. Although autoantibodies against other TRIM proteins within the C-IV family have been detected in the sera of patients with primary SS, their clinical relevance remains unclear. This study was undertaken to investigate the frequency of anti-TRIM38 in patients with prim ...[more]

PMID: 26636433

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Project description:BACKGROUND:Several members of the tripartite motif-containing (TRIM) protein family have been reported to serve as vital regulators of tumorigenesis. Recent studies have demonstrated an oncogenic role of TRIM 14 in multiple human cancers; however, the importance of this protein in glioblastoma remains to be elucidated. METHODS:The expression levels of TRIM14 were analyzed in a series of database and were examined in a variety of glioblastoma cell lines. Two independent TRIM14 shRNA were transfected into LN229 and U251 cells, and the effect of TRIM14 depletion was confirmed. Transwell assay and wound healing assay assay were carried out to assess the effect of TRIM14 depletion on glioblastoma cell invasion and migration. Western blotting was performed to screen the downstream gene of TRIM14. The stability analysis and Ubiquitylation assays and Orthotopic xenograft studies were also performed to investigate the role of TRIM14 and the relationship with downstream gene. Human glioblastoma tissues were obtained and immunohistochemical staining were carried out to confirm the clinical significance of TRIM14. RESULTS:In this study, we showed that TRIM14 was upregulated in human glioblastoma specimens and cell lines, and correlated with glioblastoma progression and shorter patient survival times. Functional experiments showed that decreased TRIM14 expression reduced glioblastoma cell invasion and migration. Furthermore, we identified that zinc finger E-box binding homeobox 2 (ZEB2), a transcription factor involved in epithelial-mesenchymal transition, is a downstream target of TRIM14. Further investigation revealed that TRIM14 inactivation significantly facilitated ZEB2 ubiquitination and proteasomal degradation, which led to aggressive invasion and migration. Our findings provide insight into the specific biological role of TRIM14 in tumor invasion. CONCLUSIONS:Our findings provide insight into the specific biological role of TRIM14 in tumor invasion, and suggest that targeting the TRIM14/ZEB2 axis might be a novel therapeutic approach for blocking glioblastoma.

Dataset Information

Brief Report: Patients With Primary Sjogren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity.

Publications

Brief Report: Patients With Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity.

Similar Datasets

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