SOX‐5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women
Objective Adaptive immunity mediates psoriatic disease pathogenesis. We aimed to identify novel psoriatic autoantigens and their phenotypic associations in deeply characterized patient cohorts. Methods Sera from psoriatic arthritis (PsA) patients were used for autoantibody discovery. Immunoprecipita...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-12-01
|
| Series: | ACR Open Rheumatology |
| Online Access: | https://doi.org/10.1002/acr2.11740 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850062660881612800 |
|---|---|
| author | Ana‐Maria Orbai David Fiorentino Jamie Perin Erika Darrah Qingyuan Yang Laura Gutierrez‐Alamillo Clifton O. Bingham Michelle Petri Antony Rosen Livia Casciola‐Rosen |
| author_facet | Ana‐Maria Orbai David Fiorentino Jamie Perin Erika Darrah Qingyuan Yang Laura Gutierrez‐Alamillo Clifton O. Bingham Michelle Petri Antony Rosen Livia Casciola‐Rosen |
| author_sort | Ana‐Maria Orbai |
| collection | DOAJ |
| description | Objective Adaptive immunity mediates psoriatic disease pathogenesis. We aimed to identify novel psoriatic autoantigens and their phenotypic associations in deeply characterized patient cohorts. Methods Sera from psoriatic arthritis (PsA) patients were used for autoantibody discovery. Immunoprecipitations performed with cell lysates were on‐bead digested, and autoantigens were identified by mass spectrometry. Prevalence and clinical features associated with anti–SRY‐Box transcription factor‐D (SOX‐D) antibodies were determined by screening discovery cohorts of patients with PsA (n = 135), patients with psoriasis without PsA (n = 24), and healthy controls (n = 41). A PsA validation cohort (n = 325) and disease control samples of individuals with rheumatoid arthritis (RA; n = 66) and systemic lupus erythematosus (SLE, n = 66) were assayed for anti‐SOX5 antibodies. Disease characteristics were compared by antibody status. Longitudinal data were analyzed using linear mixed‐effects models with patient‐specific intercept to ascertain associations. We also tested PsA sera for the recently described anti–ADAMTS‐L5 autoantibody in PsA. Results The novel autoantigens identified were SOX‐D transcription factors, with SOX‐5 being the focus of this analysis. Anti‐SOX5 antibodies were present in 8.9% (12 of 135) and 4.3% (14 of 323) of patients in the PsA discovery and validation cohorts, respectively, 12.5% of patients (3 of 24) in the psoriasis group, 2.4% (1 of 41) of healthy controls, and 7.6% (5 of 66) each of patients in the RA and SLE groups. Anti‐SOX5 were associated with female sex in both PsA cohorts (discovery: 15.7% women, 2.6% men, P = 0.006; validation: 6.3% women, 1.4% men, P = 0.049). In a longitudinal analysis adjusted for sex, anti‐SOX5 associated with biologic disease‐modifying antirheumatic drug treatment (95% vs 61%; P = 0.001; n = 96) and with differences in estimated treatment effects by mechanism of action. Anti–ADAMTS‐L5 autoantibodies were identified in 8 of 124 patients (6.5%) in the PsA group. Conclusion SOX‐D transcription factors are novel psoriatic autoantigens. Anti‐SOX5 antibodies were preferentially found in women with PsA and associated with specific clinical and treatment characteristics, suggesting that anti‐SOX5 antibodies may identify mechanistic subgroups. We independently validated anti–ADAMTS‐L5 autoantibodies in PsA. |
| format | Article |
| id | doaj-art-8d5ec29fda92410cb0eb4da5864aef94 |
| institution | DOAJ |
| issn | 2578-5745 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | ACR Open Rheumatology |
| spelling | doaj-art-8d5ec29fda92410cb0eb4da5864aef942025-08-20T02:49:52ZengWileyACR Open Rheumatology2578-57452024-12-0161280781910.1002/acr2.11740SOX‐5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in WomenAna‐Maria Orbai0David Fiorentino1Jamie Perin2Erika Darrah3Qingyuan Yang4Laura Gutierrez‐Alamillo5Clifton O. Bingham6Michelle Petri7Antony Rosen8Livia Casciola‐Rosen9Johns Hopkins University School of Medicine Baltimore MarylandStanford University School of Medicine Stanford CaliforniaJohns Hopkins University School of Public Health Baltimore MarylandJohns Hopkins University School of Medicine Baltimore MarylandJohns Hopkins University School of Medicine Baltimore MarylandJohns Hopkins University School of Medicine Baltimore MarylandJohns Hopkins University School of Medicine Baltimore MarylandJohns Hopkins University School of Medicine Baltimore MarylandJohns Hopkins University School of Medicine Baltimore MarylandJohns Hopkins University School of Medicine Baltimore MarylandObjective Adaptive immunity mediates psoriatic disease pathogenesis. We aimed to identify novel psoriatic autoantigens and their phenotypic associations in deeply characterized patient cohorts. Methods Sera from psoriatic arthritis (PsA) patients were used for autoantibody discovery. Immunoprecipitations performed with cell lysates were on‐bead digested, and autoantigens were identified by mass spectrometry. Prevalence and clinical features associated with anti–SRY‐Box transcription factor‐D (SOX‐D) antibodies were determined by screening discovery cohorts of patients with PsA (n = 135), patients with psoriasis without PsA (n = 24), and healthy controls (n = 41). A PsA validation cohort (n = 325) and disease control samples of individuals with rheumatoid arthritis (RA; n = 66) and systemic lupus erythematosus (SLE, n = 66) were assayed for anti‐SOX5 antibodies. Disease characteristics were compared by antibody status. Longitudinal data were analyzed using linear mixed‐effects models with patient‐specific intercept to ascertain associations. We also tested PsA sera for the recently described anti–ADAMTS‐L5 autoantibody in PsA. Results The novel autoantigens identified were SOX‐D transcription factors, with SOX‐5 being the focus of this analysis. Anti‐SOX5 antibodies were present in 8.9% (12 of 135) and 4.3% (14 of 323) of patients in the PsA discovery and validation cohorts, respectively, 12.5% of patients (3 of 24) in the psoriasis group, 2.4% (1 of 41) of healthy controls, and 7.6% (5 of 66) each of patients in the RA and SLE groups. Anti‐SOX5 were associated with female sex in both PsA cohorts (discovery: 15.7% women, 2.6% men, P = 0.006; validation: 6.3% women, 1.4% men, P = 0.049). In a longitudinal analysis adjusted for sex, anti‐SOX5 associated with biologic disease‐modifying antirheumatic drug treatment (95% vs 61%; P = 0.001; n = 96) and with differences in estimated treatment effects by mechanism of action. Anti–ADAMTS‐L5 autoantibodies were identified in 8 of 124 patients (6.5%) in the PsA group. Conclusion SOX‐D transcription factors are novel psoriatic autoantigens. Anti‐SOX5 antibodies were preferentially found in women with PsA and associated with specific clinical and treatment characteristics, suggesting that anti‐SOX5 antibodies may identify mechanistic subgroups. We independently validated anti–ADAMTS‐L5 autoantibodies in PsA.https://doi.org/10.1002/acr2.11740 |
| spellingShingle | Ana‐Maria Orbai David Fiorentino Jamie Perin Erika Darrah Qingyuan Yang Laura Gutierrez‐Alamillo Clifton O. Bingham Michelle Petri Antony Rosen Livia Casciola‐Rosen SOX‐5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women ACR Open Rheumatology |
| title | SOX‐5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women |
| title_full | SOX‐5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women |
| title_fullStr | SOX‐5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women |
| title_full_unstemmed | SOX‐5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women |
| title_short | SOX‐5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women |
| title_sort | sox 5 transcription factor a novel psoriatic autoantigen preferentially found in women |
| url | https://doi.org/10.1002/acr2.11740 |
| work_keys_str_mv | AT anamariaorbai sox5transcriptionfactoranovelpsoriaticautoantigenpreferentiallyfoundinwomen AT davidfiorentino sox5transcriptionfactoranovelpsoriaticautoantigenpreferentiallyfoundinwomen AT jamieperin sox5transcriptionfactoranovelpsoriaticautoantigenpreferentiallyfoundinwomen AT erikadarrah sox5transcriptionfactoranovelpsoriaticautoantigenpreferentiallyfoundinwomen AT qingyuanyang sox5transcriptionfactoranovelpsoriaticautoantigenpreferentiallyfoundinwomen AT lauragutierrezalamillo sox5transcriptionfactoranovelpsoriaticautoantigenpreferentiallyfoundinwomen AT cliftonobingham sox5transcriptionfactoranovelpsoriaticautoantigenpreferentiallyfoundinwomen AT michellepetri sox5transcriptionfactoranovelpsoriaticautoantigenpreferentiallyfoundinwomen AT antonyrosen sox5transcriptionfactoranovelpsoriaticautoantigenpreferentiallyfoundinwomen AT liviacasciolarosen sox5transcriptionfactoranovelpsoriaticautoantigenpreferentiallyfoundinwomen |