Patients with Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity

Nina Wolska, Paulina Rybakowska, Astrid Rasmussen, Michael Brown, Courtney Montgomery, Arkadiusz Klopocki, Kiely Grundahl, Robert H. Scofield, Lida Radfar, Donald U. Stone, Juan M. Anaya, John A. Ice, Christopher J. Lessard, David M. Lewis, Nelson L. Rhodus, Rajaram Gopalakrishnan, Andrew J.W. Huang, Pamela J. Hughes, Michael D. Rohrer, Michael H. Weisman & 6 others Swamy Venuturupalli, Joel M. Guthridge, Judith A. James, Kathy L. Sivils, Harini Bagavant, Umesh S. Deshmukh

Research output: Contribution to journalArticle

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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. Conclusion Our data demonstrate that anti-TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease.

Original languageEnglish (US)
Pages (from-to)724-729
Number of pages6
JournalArthritis and Rheumatology
Volume68
Issue number3
DOIs
StatePublished - Mar 1 2016

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Autoantibodies
Anti-Idiotypic Antibodies
Cortactin
Serum
Minor Salivary Glands
Hypergammaglobulinemia
Amino Acids
Antibody Affinity
Rheumatoid Factor
Lip
Protein C
Tripartite Motif Proteins
Methionine
Carrier Proteins
Staining and Labeling
Biopsy
Proteins

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Patients with Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity. / Wolska, Nina; Rybakowska, Paulina; Rasmussen, Astrid; Brown, Michael; Montgomery, Courtney; Klopocki, Arkadiusz; Grundahl, Kiely; Scofield, Robert H.; Radfar, Lida; Stone, Donald U.; Anaya, Juan M.; Ice, John A.; Lessard, Christopher J.; Lewis, David M.; Rhodus, Nelson L.; Gopalakrishnan, Rajaram; Huang, Andrew J.W.; Hughes, Pamela J.; Rohrer, Michael D.; Weisman, Michael H.; Venuturupalli, Swamy; Guthridge, Joel M.; James, Judith A.; Sivils, Kathy L.; Bagavant, Harini; Deshmukh, Umesh S.

In: Arthritis and Rheumatology, Vol. 68, No. 3, 01.03.2016, p. 724-729.

Research output: Contribution to journalArticle

Wolska, N, Rybakowska, P, Rasmussen, A, Brown, M, Montgomery, C, Klopocki, A, Grundahl, K, Scofield, RH, Radfar, L, Stone, DU, Anaya, JM, Ice, JA, Lessard, CJ, Lewis, DM, Rhodus, NL, Gopalakrishnan, R, Huang, AJW, Hughes, PJ, Rohrer, MD, Weisman, MH, Venuturupalli, S, Guthridge, JM, James, JA, Sivils, KL, Bagavant, H & Deshmukh, US 2016, 'Patients with Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity', Arthritis and Rheumatology, vol. 68, no. 3, pp. 724-729. https://doi.org/10.1002/art.39497
Wolska, Nina ; Rybakowska, Paulina ; Rasmussen, Astrid ; Brown, Michael ; Montgomery, Courtney ; Klopocki, Arkadiusz ; Grundahl, Kiely ; Scofield, Robert H. ; Radfar, Lida ; Stone, Donald U. ; Anaya, Juan M. ; Ice, John A. ; Lessard, Christopher J. ; Lewis, David M. ; Rhodus, Nelson L. ; Gopalakrishnan, Rajaram ; Huang, Andrew J.W. ; Hughes, Pamela J. ; Rohrer, Michael D. ; Weisman, Michael H. ; Venuturupalli, Swamy ; Guthridge, Joel M. ; James, Judith A. ; Sivils, Kathy L. ; Bagavant, Harini ; Deshmukh, Umesh S. / Patients with Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity. In: Arthritis and Rheumatology. 2016 ; Vol. 68, No. 3. pp. 724-729.
@article{270c0d155b8f4b689f113443e97973b5,
title = "Patients with Primary Sj{\"o}gren'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 Sj{\"o}gren'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. Conclusion Our data demonstrate that anti-TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease.",
author = "Nina Wolska and Paulina Rybakowska and Astrid Rasmussen and Michael Brown and Courtney Montgomery and Arkadiusz Klopocki and Kiely Grundahl and Scofield, {Robert H.} and Lida Radfar and Stone, {Donald U.} and Anaya, {Juan M.} and Ice, {John A.} and Lessard, {Christopher J.} and Lewis, {David M.} and Rhodus, {Nelson L.} and Rajaram Gopalakrishnan and Huang, {Andrew J.W.} and Hughes, {Pamela J.} and Rohrer, {Michael D.} and Weisman, {Michael H.} and Swamy Venuturupalli and Guthridge, {Joel M.} and James, {Judith A.} and Sivils, {Kathy L.} and Harini Bagavant and Deshmukh, {Umesh S.}",
year = "2016",
month = "3",
day = "1",
doi = "10.1002/art.39497",
language = "English (US)",
volume = "68",
pages = "724--729",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - Patients with Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity

AU - Wolska, Nina

AU - Rybakowska, Paulina

AU - Rasmussen, Astrid

AU - Brown, Michael

AU - Montgomery, Courtney

AU - Klopocki, Arkadiusz

AU - Grundahl, Kiely

AU - Scofield, Robert H.

AU - Radfar, Lida

AU - Stone, Donald U.

AU - Anaya, Juan M.

AU - Ice, John A.

AU - Lessard, Christopher J.

AU - Lewis, David M.

AU - Rhodus, Nelson L.

AU - Gopalakrishnan, Rajaram

AU - Huang, Andrew J.W.

AU - Hughes, Pamela J.

AU - Rohrer, Michael D.

AU - Weisman, Michael H.

AU - Venuturupalli, Swamy

AU - Guthridge, Joel M.

AU - James, Judith A.

AU - Sivils, Kathy L.

AU - Bagavant, Harini

AU - Deshmukh, Umesh S.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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. Conclusion Our data demonstrate that anti-TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease.

AB - 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. Conclusion Our data demonstrate that anti-TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease.

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U2 - 10.1002/art.39497

DO - 10.1002/art.39497

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VL - 68

SP - 724

EP - 729

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

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