Abstract
Objective: Scleroderma patients with autoantibodies to CENPs and/or interferon-inducible protein 16 (IFI-16) are at increased risk of severe vascular complications. This study was undertaken to determine whether these autoantigens are enriched in cells of the vasculature. Methods: Successive stages of embryoid bodies (EBs) as well as vascular progenitors were used to evaluate the expression of scleroderma autoantigens IFI-16 and CENP by immunoblotting. CD31 was included to mark early blood vessels. IFI-16 and CD31 expression were defined in paraffin-embedded skin sections from scleroderma patients and from healthy controls. IFI-16 expression was determined by flow cytometric analysis in circulating endothelial cells (CECs) and circulating hematopoietic progenitor cells. Results: Expression of CENP-A, IFI-16, and CD31 was enriched in EBs on days 10 and 12 of differentiation, and particularly in cultures enriched in vascular progenitors (IFI-16, CD31, and CENPs A and B). This pattern was distinct from that of comparator autoantigens. Immunohistochemical staining of paraffin-embedded skin sections showed enrichment of IFI-16 in CD31-positive vascular endothelial cells in biopsy specimens from scleroderma patients and normal controls. Flow cytometric analysis revealed IFI-16 expression in circulating hematopoietic progenitor cells but minimal expression in CECs. Conclusion: Our findings indicate that expression of the scleroderma autoantigens IFI-16 and CENPs, which are associated with severe vascular disease, is increased in vascular progenitors and mature endothelial cells. High level, lineage-enriched expression of autoantigens may explain the striking association between clinical phenotypes and the immune targeting of specific autoantigens.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2540-2549 |
| Number of pages | 10 |
| Journal | Arthritis and Rheumatology |
| Volume | 68 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2016 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Rheumatology
- Immunology
Cite this
Enrichment of Scleroderma Vascular Disease–Associated Autoantigens in Endothelial Lineage Cells. / McMahan, Zsuzsanna; Cottrell, Tricia R.; Wigley, Fredrick; Antiochos, Brendan; Zambidis, Elias; Park, Tea Soon; Halushka, Marc K; Gutierrez, Laura; Cimbro, Raffaello; Rosen, Antony; Casciola Rosen, Livia A.
In: Arthritis and Rheumatology, Vol. 68, No. 10, 01.10.2016, p. 2540-2549.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enrichment of Scleroderma Vascular Disease–Associated Autoantigens in Endothelial Lineage Cells
AU - McMahan, Zsuzsanna
AU - Cottrell, Tricia R.
AU - Wigley, Fredrick
AU - Antiochos, Brendan
AU - Zambidis, Elias
AU - Park, Tea Soon
AU - Halushka, Marc K
AU - Gutierrez, Laura
AU - Cimbro, Raffaello
AU - Rosen, Antony
AU - Casciola Rosen, Livia A
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Objective: Scleroderma patients with autoantibodies to CENPs and/or interferon-inducible protein 16 (IFI-16) are at increased risk of severe vascular complications. This study was undertaken to determine whether these autoantigens are enriched in cells of the vasculature. Methods: Successive stages of embryoid bodies (EBs) as well as vascular progenitors were used to evaluate the expression of scleroderma autoantigens IFI-16 and CENP by immunoblotting. CD31 was included to mark early blood vessels. IFI-16 and CD31 expression were defined in paraffin-embedded skin sections from scleroderma patients and from healthy controls. IFI-16 expression was determined by flow cytometric analysis in circulating endothelial cells (CECs) and circulating hematopoietic progenitor cells. Results: Expression of CENP-A, IFI-16, and CD31 was enriched in EBs on days 10 and 12 of differentiation, and particularly in cultures enriched in vascular progenitors (IFI-16, CD31, and CENPs A and B). This pattern was distinct from that of comparator autoantigens. Immunohistochemical staining of paraffin-embedded skin sections showed enrichment of IFI-16 in CD31-positive vascular endothelial cells in biopsy specimens from scleroderma patients and normal controls. Flow cytometric analysis revealed IFI-16 expression in circulating hematopoietic progenitor cells but minimal expression in CECs. Conclusion: Our findings indicate that expression of the scleroderma autoantigens IFI-16 and CENPs, which are associated with severe vascular disease, is increased in vascular progenitors and mature endothelial cells. High level, lineage-enriched expression of autoantigens may explain the striking association between clinical phenotypes and the immune targeting of specific autoantigens.
AB - Objective: Scleroderma patients with autoantibodies to CENPs and/or interferon-inducible protein 16 (IFI-16) are at increased risk of severe vascular complications. This study was undertaken to determine whether these autoantigens are enriched in cells of the vasculature. Methods: Successive stages of embryoid bodies (EBs) as well as vascular progenitors were used to evaluate the expression of scleroderma autoantigens IFI-16 and CENP by immunoblotting. CD31 was included to mark early blood vessels. IFI-16 and CD31 expression were defined in paraffin-embedded skin sections from scleroderma patients and from healthy controls. IFI-16 expression was determined by flow cytometric analysis in circulating endothelial cells (CECs) and circulating hematopoietic progenitor cells. Results: Expression of CENP-A, IFI-16, and CD31 was enriched in EBs on days 10 and 12 of differentiation, and particularly in cultures enriched in vascular progenitors (IFI-16, CD31, and CENPs A and B). This pattern was distinct from that of comparator autoantigens. Immunohistochemical staining of paraffin-embedded skin sections showed enrichment of IFI-16 in CD31-positive vascular endothelial cells in biopsy specimens from scleroderma patients and normal controls. Flow cytometric analysis revealed IFI-16 expression in circulating hematopoietic progenitor cells but minimal expression in CECs. Conclusion: Our findings indicate that expression of the scleroderma autoantigens IFI-16 and CENPs, which are associated with severe vascular disease, is increased in vascular progenitors and mature endothelial cells. High level, lineage-enriched expression of autoantigens may explain the striking association between clinical phenotypes and the immune targeting of specific autoantigens.
UR - http://www.scopus.com/inward/record.url?scp=84988891881&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84988891881&partnerID=8YFLogxK
U2 - 10.1002/art.39743
DO - 10.1002/art.39743
M3 - Article
C2 - 27159521
AN - SCOPUS:84988891881
VL - 68
SP - 2540
EP - 2549
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 10
ER -