Live rubella virus vaccine long-term persistence as an antigenic trigger of cutaneous granulomas in patients with primary immunodeficiency

被引:65
作者
Bodemer, C. [1 ,2 ,3 ]
Sauvage, V. [4 ]
Mahlaoui, N. [5 ,6 ]
Cheval, J. [4 ]
Couderc, T. [8 ,9 ]
Leclerc-Mercier, S. [1 ,2 ,10 ]
Debre, M. [5 ]
Pellier, I. [11 ]
Gagnieur, L. [12 ]
Fraitag, S. [2 ,10 ]
Fischer, A. [3 ,5 ,6 ,7 ]
Blanche, S. [3 ,5 ,6 ]
Lecuit, M. [3 ,6 ,8 ,9 ,13 ]
Eloit, M. [4 ,12 ,14 ]
机构
[1] Necker Enfants Malad Univ Hosp, APHP, Dept Dermatol, Paris, France
[2] Reference Ctr Cutaneous Rare Dis MAGEC, Paris, France
[3] Univ Paris 05, Inst Imagine, Sorbonne Paris Cite, Paris, France
[4] PathoQuest, Paris, France
[5] Necker Enfants Malad Univ Hosp, APHP, Paediat Haematoimmunol Unit, Paris, France
[6] Necker Enfants Malad Univ Hosp, APHP, Natl Reference Ctr Primary Immune Deficiencies CE, Paris, France
[7] Inserm U768, Paris, France
[8] Inst Pasteur, Biol Infect Unit, Paris, France
[9] Inserm U1117, Paris, France
[10] Necker Enfants Malad Univ Hosp, APHP, Dept Pathol, Paris, France
[11] CHU Angers, Haematol Immunol Oncol Paediat Unit, Paris, France
[12] Inst Pasteur, Dept Virol, Lab Pathogen Discovery, 28 Rue Docteur Roux, F-75724 Paris, France
[13] Necker Enfants Malad Univ Hosp, APHP, Div Infect Dis & Trop Med, Paris, France
[14] Ecole Natl Vet Alfort UMR 1161 Virol ENVA, INRA, ANSES, Maisons Alfort, France
基金
欧洲研究理事会;
关键词
REPLICATION; MUTATIONS; LESIONS; SKIN;
D O I
10.1111/1469-0691.12573
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Granulomas may develop as a response to a local antigenic trigger, leading to the activation of macrophages and T-lymphocytes. Primary immunodeficiency (PID) is associated with the development of extensive cutaneous granulomas, whose aetiology remains unknown. We performed high-throughput sequencing of the transcriptome of cutaneous granuloma lesions on two consecutive index cases, and RT-PCR in a third consecutive patient. The RA27/3 vaccine strain of rubella virusthe core component of a universally used paediatric vaccinewas present in the cutaneous granuloma of these three consecutive PID patients. Controls included the healthy skin of two patients, non-granulomatous cutaneous lesions of patients with immunodeficiency, and skin biopsy samples of healthy individuals, and were negative. Expression of viral antigens was confirmed by immunofluorescence. Persistence of the rubella vaccine virus was also demonstrated in granuloma lesions sampled 4-5years earlier. The persistence of the rubella virus vaccine strain in all three consecutive cutaneous granuloma patients with PID strongly suggests a causal relationship between rubella virus and granuloma in this setting.
引用
收藏
页码:O656 / O663
页数:8
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