Serum and tear autoantibodies from NOD and NOR mice as potential diagnostic indicators of local and systemic inflammation in Sjögren’s disease
BackgroundSjögren’s Disease (SjD) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands (LG). The LG produces the protein-rich aqueous component of tears, and SjD-associated autoimmune dacryoadenitis (AD) may thus alter tear autoantibody composition.Metho...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1516330/full |
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| author | Shruti Singh Kakan Sara Abdelhamid Sara Abdelhamid Yaping Ju Yaping Ju J. Andrew MacKay J. Andrew MacKay J. Andrew MacKay Maria C. Edman Indu Raman Chengsong Zhu Prithvi Raj Sarah F. Hamm-Alvarez Sarah F. Hamm-Alvarez |
| author_facet | Shruti Singh Kakan Sara Abdelhamid Sara Abdelhamid Yaping Ju Yaping Ju J. Andrew MacKay J. Andrew MacKay J. Andrew MacKay Maria C. Edman Indu Raman Chengsong Zhu Prithvi Raj Sarah F. Hamm-Alvarez Sarah F. Hamm-Alvarez |
| author_sort | Shruti Singh Kakan |
| collection | DOAJ |
| description | BackgroundSjögren’s Disease (SjD) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands (LG). The LG produces the protein-rich aqueous component of tears, and SjD-associated autoimmune dacryoadenitis (AD) may thus alter tear autoantibody composition.MethodsThe presence of tertiary lymphoid structures (TLS) in LG from two murine models of SjD-associated AD, male non-obese diabetic (NOD) and male non-obese insulitis resistant (NOR) mice, were evaluated using immunofluorescence. IgG and IgA reactivity in serum and tears from these models were probed in three studies against a panel of 80-120 autoantigens using autoantibody microarrays relative to serum and tears from healthy male BALB/c mice. Sources of Ig in tears were investigated using scRNA-Seq of the LG (GSE132420). Data were analyzed by R package Limma and Seurat.ResultsAnalysis of immunofluorescence in LG sections from both SjD models showed TLS. Only one autoantibody was significantly elevated in tears and serum in both SjD models across all studies. Three autoantibodies were significantly elevated in serum but not in tears in both SjD models across all studies. Conversely, six IgG and thirteen IgA autoantibodies (6 sharing the same autoantigen) were significantly elevated in tears but not serum in both SjD models. Igha and Ighg2b expressing cells were identified in the plasma cell cluster of NOD.H2b LG.ConclusionNOD and NOR mice with SjD-associated AD have distinct autoantibody profiles in tears and serum. Tear IgA isotype autoantibodies showed a greater diversity than tear IgG autoantibodies. TLS observed in LG are a likely source of the tear autoantibodies. |
| format | Article |
| id | doaj-art-5d7cbe39ba614e319394e51ade5b942c |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-5d7cbe39ba614e319394e51ade5b942c2025-01-28T06:41:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15163301516330Serum and tear autoantibodies from NOD and NOR mice as potential diagnostic indicators of local and systemic inflammation in Sjögren’s diseaseShruti Singh Kakan0Sara Abdelhamid1Sara Abdelhamid2Yaping Ju3Yaping Ju4J. Andrew MacKay5J. Andrew MacKay6J. Andrew MacKay7Maria C. Edman8Indu Raman9Chengsong Zhu10Prithvi Raj11Sarah F. Hamm-Alvarez12Sarah F. Hamm-Alvarez13Department of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Pharmacology & Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United StatesDepartment of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Pharmacology & Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United StatesDepartment of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Pharmacology & Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United StatesAlfred E. Mann Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, United StatesDepartment of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Immunology, Microarray and Immune Phenotyping Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Immunology, Microarray and Immune Phenotyping Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Immunology, Microarray and Immune Phenotyping Core Facility, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Pharmacology & Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, United StatesBackgroundSjögren’s Disease (SjD) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands (LG). The LG produces the protein-rich aqueous component of tears, and SjD-associated autoimmune dacryoadenitis (AD) may thus alter tear autoantibody composition.MethodsThe presence of tertiary lymphoid structures (TLS) in LG from two murine models of SjD-associated AD, male non-obese diabetic (NOD) and male non-obese insulitis resistant (NOR) mice, were evaluated using immunofluorescence. IgG and IgA reactivity in serum and tears from these models were probed in three studies against a panel of 80-120 autoantigens using autoantibody microarrays relative to serum and tears from healthy male BALB/c mice. Sources of Ig in tears were investigated using scRNA-Seq of the LG (GSE132420). Data were analyzed by R package Limma and Seurat.ResultsAnalysis of immunofluorescence in LG sections from both SjD models showed TLS. Only one autoantibody was significantly elevated in tears and serum in both SjD models across all studies. Three autoantibodies were significantly elevated in serum but not in tears in both SjD models across all studies. Conversely, six IgG and thirteen IgA autoantibodies (6 sharing the same autoantigen) were significantly elevated in tears but not serum in both SjD models. Igha and Ighg2b expressing cells were identified in the plasma cell cluster of NOD.H2b LG.ConclusionNOD and NOR mice with SjD-associated AD have distinct autoantibody profiles in tears and serum. Tear IgA isotype autoantibodies showed a greater diversity than tear IgG autoantibodies. TLS observed in LG are a likely source of the tear autoantibodies.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1516330/fullSjögren’s diseaseautoimmune diseaseIgA autoantibodiesIgG autoantibodiestear filmserum |
| spellingShingle | Shruti Singh Kakan Sara Abdelhamid Sara Abdelhamid Yaping Ju Yaping Ju J. Andrew MacKay J. Andrew MacKay J. Andrew MacKay Maria C. Edman Indu Raman Chengsong Zhu Prithvi Raj Sarah F. Hamm-Alvarez Sarah F. Hamm-Alvarez Serum and tear autoantibodies from NOD and NOR mice as potential diagnostic indicators of local and systemic inflammation in Sjögren’s disease Frontiers in Immunology Sjögren’s disease autoimmune disease IgA autoantibodies IgG autoantibodies tear film serum |
| title | Serum and tear autoantibodies from NOD and NOR mice as potential diagnostic indicators of local and systemic inflammation in Sjögren’s disease |
| title_full | Serum and tear autoantibodies from NOD and NOR mice as potential diagnostic indicators of local and systemic inflammation in Sjögren’s disease |
| title_fullStr | Serum and tear autoantibodies from NOD and NOR mice as potential diagnostic indicators of local and systemic inflammation in Sjögren’s disease |
| title_full_unstemmed | Serum and tear autoantibodies from NOD and NOR mice as potential diagnostic indicators of local and systemic inflammation in Sjögren’s disease |
| title_short | Serum and tear autoantibodies from NOD and NOR mice as potential diagnostic indicators of local and systemic inflammation in Sjögren’s disease |
| title_sort | serum and tear autoantibodies from nod and nor mice as potential diagnostic indicators of local and systemic inflammation in sjogren s disease |
| topic | Sjögren’s disease autoimmune disease IgA autoantibodies IgG autoantibodies tear film serum |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1516330/full |
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