title: Clinical and immunological insights on severe, adverse neurotropic and viscerotropic disease following 17D yellow fever vaccination.
abstract: Yellow fever (YF) vaccines (17D-204 and 17DD) are well tolerated and cause very low rates of severe adverse events (YEL-SAE), such as serious allergic reactions, neurotropic adverse diseases (YEL-AND), and viscerotropic diseases (YEL-AVD). Viral and host factors have been postulated to explain the basis of YEL-SAE. However, the mechanisms underlying the occurrence of YEL-SAE remain unknown. The present report provides a detailed immunological analysis of a 23-year-old female patient. The patient developed a suspected case of severe YEL-AVD with encephalitis, as well as with pancreatitis and myositis, following receipt of a 17D-204 YF vaccination. The patient exhibited a decreased level of expression of Fc-gammaR in monocytes (CD16, CD32, and CD64), along with increased levels of NK T cells (an increased CD3(+) CD16(+/-) CD56(+/-)/CD3(+) ratio), activated T cells (CD4(+) and CD8(+) cells), and B lymphocytes. Enhanced levels of plasmatic cytokines (interleukin-6 [IL-6], IL-17, IL-4, IL-5, and IL-10) as well as an exacerbated ex vivo intracytoplasmic cytokine pattern, mainly observed within NK cells (gamma interferon positive [IFN-gamma(+)], tumor necrosis factor alpha positive [TNF-alpha(+)], and IL-4 positive [IL-4(+)]), CD8(+) T cells (IL-4(+) and IL-5(+)), and B lymphocytes (TNF-alpha(+), IL-4(+), and IL-10(+)). The analysis of CD4(+) T cells revealed a complex profile that consisted of an increased frequency of IL-12(+) and IFN-gamma(+) cells and a decreased percentage of TNF-alpha(+), IL-4(+), and IL-5(+) cells. Depressed cytokine synthesis was observed in monocytes (TNF-alpha(+)) following the provision of antigenic stimuli in vitro. These results support the hypothesis that a strong adaptive response and abnormalities in the innate immune system may be involved in the establishment of YEL-AND and YEL-AVD.
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, FIOCRUZ/Minas, Avenida Augusto de Lima 1715, Barro Preto, Belo Horizonte, Minas Gerais 30190-002, Brazil.
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Silva
authors.forename: Luçandra Ramos
authors.initials: LR
authors.lastname: Espírito-Santo
authors.forename: Marina Angela
authors.initials: MA
authors.lastname: Martins
authors.forename: Denise
authors.initials: D
authors.lastname: Silveira-Lemos
authors.forename: Vanessa
authors.initials: V
authors.lastname: Peruhype-Magalhães
authors.forename: Ricardo Carvalho
authors.initials: RC
authors.lastname: Caminha
authors.forename: Péricles
authors.initials: P
authors.lastname: de Andrade Maranhão-Filho
authors.forename: Maria
authors.initials: M
authors.lastname: Auxiliadora-Martins
authors.forename: Reinaldo
authors.initials: R
authors.lastname: de Menezes Martins
authors.forename: Ricardo
authors.initials: R
authors.lastname: Galler
authors.forename: Marcos
authors.initials: M
authors.lastname: da Silva Freire
authors.forename: Rugimar
authors.initials: R
authors.lastname: Marcovistz
authors.forename: Akira
authors.initials: A
authors.lastname: Homma
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Teuwen
authors.forename: Silvana Maria
authors.initials: SM
authors.lastname: Elói-Santos
authors.forename: Mariléia Chaves
authors.initials: MC
authors.lastname: Andrade
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000276:immunology* / Q000473:pathology*; D004660:Encephalitis / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology; D009000:Monocytes / Q000737:chemistry / Q000276:immunology; D009220:Myositis / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D022341:Yellow Fever Vaccine / Q000009:adverse effects* / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D022341:Yellow Fever Vaccine