title: Brief Report: Patients With Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our data demonstrate that anti-TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease.
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Nina
authors.initials: N
authors.lastname: Wolska
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Paulina
authors.initials: P
authors.lastname: Rybakowska
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Astrid
authors.initials: A
authors.lastname: Rasmussen
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Michael
authors.initials: M
authors.lastname: Brown
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Courtney
authors.initials: C
authors.lastname: Montgomery
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Klopocki
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Kiely
authors.initials: K
authors.lastname: Grundahl
authors.affiliation: Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, and VAMC, Oklahoma City.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Scofield
authors.affiliation: University of Oklahoma College of Dentistry, Oklahoma City.
authors.forename: Lida
authors.initials: L
authors.lastname: Radfar
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Donald U
authors.initials: DU
authors.lastname: Stone
authors.affiliation: Universidad del Rosario, Bogota, Colombia.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Anaya
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: John A
authors.initials: JA
authors.lastname: Ice
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lessard
authors.affiliation: University of Oklahoma College of Dentistry, Oklahoma City.
authors.forename: David M
authors.initials: DM
authors.lastname: Lewis
authors.affiliation: University of Minnesota School of Dentistry, Minneapolis.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Rhodus
authors.affiliation: University of Minnesota School of Dentistry, Minneapolis.
authors.forename: Rajaram
authors.initials: R
authors.lastname: Gopalakrishnan
authors.affiliation: Washington University, St. Louis, Missouri.
authors.forename: Andrew J W
authors.initials: AJ
authors.lastname: Huang
authors.affiliation: University of Minnesota School of Dentistry, Minneapolis.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hughes
authors.affiliation: University of Minnesota School of Dentistry, Minneapolis.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Rohrer
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Weisman
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Swamy
authors.initials: S
authors.lastname: Venuturupalli
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Guthridge
authors.affiliation: Oklahoma Medical Research Foundation and University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Sivils
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Harini
authors.initials: H
authors.lastname: Bagavant
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Umesh S
authors.initials: US
authors.lastname: Deshmukh
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D002352:Carrier Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D006942:Hypergammaglobulinemia / Q000276:immunology; D047468:Immunoprecipitation; D008297:Male; D008715:Methionine; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood; D012261:Ribonucleoproteins / Q000276:immunology; D012720:Severity of Illness Index; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000503:physiopathology; D013462:Sulfur Radioisotopes; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D000099207:SS-A Antigen
chemical_list: D001323:Autoantibodies; D002352:Carrier Proteins; D008715:Methionine; D012217:Rheumatoid Factor; D012261:Ribonucleoproteins; D013462:Sulfur Radioisotopes; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D000099207:SS-A Antigen; C106984:TRIM38 protein, human