ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 987

Novel Auto-Antigen in Aortic Aneurysms of Large Vessel Vasculitis

Ritu Chakravarti1, Karishma Gupta2, Jaclyn Scholtz3, Edward Soltesz4, Eric Roselli5, Gosta Pettersson4, Lars Svensson5, Douglas Johnston4, Belinda Willard6, Michifumi Yamashita7, Thomas Daly8 and Gary S. Hoffman9, 1Pathobiology, Assistant Prof/ Project Staff, Cleveland, OH, 2Pathobiology, Technician, Cleveland, OH, 3Student, Cleveland Clinic, cleveland, OH, 4Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland, OH, 5Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland, OH, 6Cleveland Clinic Foundation, Cleveland, OH, 7Pathology, Resident, Cleveland, OH, 8Clinical Lab, Director,, Cleveland, OH, 9Center for Vasculitis Care and Research, Cleveland Clinic Foundation, Cleveland, OH

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: B cell Biology and Targets in Autoimmune Disease: Rheumatoid Arthritis and Related Diseases

Session Type: Abstract Submissions (ACR)

Background/Purpose

Large Vessel Vasculitides (LVV) are a group of autoimmune diseases characterized by injury and anatomic modifications of large vessels that may include the aorta and its branch vessels. Disease etiology is unknown.  Using samples from aorta root, ascending aorta and aorta arch surgical specimens, we sought to identify antigen targets within affected vessel walls in patients with LVV, including giant cell arteritis (GCA), Takayasu’s arteritis (TA) and isolated focal aortitis (IFA).

Methods

Thoracic aorta aneurysm specimens and autologous blood were acquired from consenting consecutive patients in whom aorta reconstruction procedures were indicated. Aorta tissues from patients with both LVV and age-, race- and gender-matched patients with non-inflammatory aneurysms, were lysed and resolved on SDS-polyacrylamide gels. Sera from study groups were used to probe antigen-antibody reactivity on  western blots followed by MS analysis to identify antigen. Additional sera samples tested included sera from diseases including medium to small vessel vasculitis, sepsis etc.

Results

We found that patients with LVV (n=17) produce antibodies to 14-3-3 proteins in the aortic wall, whereas patients with non-inflammatory matrix disorders (n=17) rarely do so. Most of the sera from other immune diseases were also negative. Anti-14-3-3 antibody production was demonstrated in all 3 forms of LVV. In each, sera contained autoantibody that was sufficient to immunoprecipitate 14-3-3 protein(s) from the aortic lysates. Antibodies to 14-3-3 were not found in sera of additional controls. Three out of seven known isoforms of 14-3-3 were found to be upregulated in LVV aortas. Most  14-3-3 Ag was found to co-localize within granulomas, chronic inflammatory cells and smooth muscle cells in  LVV.

Conclusion

This study is the first to utilize sterile, snap frozen tissue from aortic reconstruction surgeries in an attempt to identify autoantigens in LVV. 14-3-3 protein(s) appears to be a novel auto-antigen in aortic aneurysms caused by LVV. The precise role of these antibodies and 14-3-3 proteins in LVV etiology and pathogenesis deserves further study.

Disclosure:

R. Chakravarti,
None;

K. Gupta,
None;

J. Scholtz,
None;

E. Soltesz,
None;

E. Roselli,
None;

G. Pettersson,
None;

L. Svensson,
None;

D. Johnston,
None;

B. Willard,
None;

M. Yamashita,
None;

T. Daly,
None;

G. S. Hoffman,
None.

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