Stephanie M LaVergne1,2, Saori Sakabe1, Lansana Kanneh3,4, Mambu Momoh3,4,5, Foday Al-Hassan3,4, Mohamed Yilah3,4, Augustine Goba3,4, John Demby Sandi3,4, Michael Gbakie3,4, Beatrice Cubitt1, Matthew Boisen6, Jessica M Mayeux7, Ashley Smira8, Kayla Shore9, Iris Bica8, K Michael Pollard7, Juan Carlos de la Torre1, Luis M Branco6, Robert F Garry10, Donald S Grant3,4,11, John S Schieffelin8, Michael B A Oldstone1, Brian M Sullivan1. 1. Viral-Immunobiology Laboratory, Department of Immunology and Microbiology, Scripps Research, La Jolla, California, USA. 2. Division of Infectious Diseases, University of California, San Diego, La Jolla, California, USA. 3. Viral Hemorrhagic Fever Program, Kenema Government Hospital, Kenema, Sierra Leone. 4. Ministry of Health and Sanitation, Freetown, Sierra Leone. 5. Eastern Polytechnic Institute, Kenema, Sierra Leone. 6. Zalgen Labs, Germantown, USA. 7. Department of Molecular Medicine, Scripps Research, La Jolla, California, USA. 8. Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, USA. 9. Department of Tropical Medicine, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA. 10. Department of Immunology and Microbiology, Tulane University School of Medicine, New Orleans, Louisiana, USA. 11. College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
Abstract
BACKGROUND: Ebola virus (EBOV) disease has killed thousands of West and Central Africans over the past several decades. Many who survive the acute disease later experience post-Ebola syndrome, a constellation of symptoms whose causative pathogenesis is unclear. METHODS: We investigated EBOV-specific CD8+ and CD4+ T-cell responses in 37 Sierra Leonean EBOV disease survivors with (n = 19) or without (n = 18) sequelae of arthralgia and ocular symptoms. Peripheral blood mononuclear cells were infected with recombinant vesicular stomatitis virus encoding EBOV antigens. We also studied the presence of EBOV-specific immunoglobulin G, antinuclear antibodies, anti-cyclic citrullinated peptide antibodies, rheumatoid factor, complement levels, and cytokine levels in these 2 groups. RESULTS: Survivors with sequelae had a significantly higher EBOV-specific CD8+ and CD4+ T-cell response. No differences in EBOV-specific immunoglobulin G, antinuclear antibody, or anti-cyclic citrullinated peptide antibody levels were found. Survivors with sequelae showed significantly higher rheumatoid factor levels. CONCLUSION: EBOV-specific CD8+ and CD4+ T-cell responses were significantly higher in Ebola survivors with post-Ebola syndrome. These findings suggest that pathogenesis may occur as an immune-mediated disease via virus-specific T-cell immune response or that persistent antigen exposure leads to increased and sustained T-cell responses.
BACKGROUND:Ebola virus (EBOV) disease has killed thousands of West and Central Africans over the past several decades. Many who survive the acute disease later experience post-Ebola syndrome, a constellation of symptoms whose causative pathogenesis is unclear. METHODS: We investigated EBOV-specific CD8+ and CD4+ T-cell responses in 37 Sierra Leonean EBOV disease survivors with (n = 19) or without (n = 18) sequelae of arthralgia and ocular symptoms. Peripheral blood mononuclear cells were infected with recombinant vesicular stomatitis virus encoding EBOV antigens. We also studied the presence of EBOV-specific immunoglobulin G, antinuclear antibodies, anti-cyclic citrullinated peptide antibodies, rheumatoid factor, complement levels, and cytokine levels in these 2 groups. RESULTS: Survivors with sequelae had a significantly higher EBOV-specific CD8+ and CD4+ T-cell response. No differences in EBOV-specific immunoglobulin G, antinuclear antibody, or anti-cyclic citrullinated peptide antibody levels were found. Survivors with sequelae showed significantly higher rheumatoid factor levels. CONCLUSION:EBOV-specific CD8+ and CD4+ T-cell responses were significantly higher in Ebola survivors with post-Ebola syndrome. These findings suggest that pathogenesis may occur as an immune-mediated disease via virus-specific T-cell immune response or that persistent antigen exposure leads to increased and sustained T-cell responses.
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