Clinical and immunological insights on severe, adverse neurotropic and viscerotropic disease following 17D yellow fever vaccination.
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.
Silva
Maria Luiza
ML
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.
Espírito-Santo
Luçandra Ramos
LR
Martins
Marina Angela
MA
Silveira-Lemos
Denise
D
Peruhype-Magalhães
Vanessa
V
Caminha
Ricardo Carvalho
RC
de Andrade Maranhão-Filho
Péricles
P
Auxiliadora-Martins
Maria
M
de Menezes Martins
Reinaldo
R
Galler
Ricardo
R
da Silva Freire
Marcos
M
Marcovistz
Rugimar
R
Homma
Akira
A
Teuwen
Dirk E
DE
Elói-Santos
Silvana Maria
SM
Andrade
Mariléia Chaves
MC
Teixeira-Carvalho
Andréa
A
Martins-Filho
Olindo Assis
OA
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
D016207:Cytokines; D022341:Yellow Fever Vaccine