INSERM U976 HIPI, équipe INSIGHT, Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France.
Department of Clinical Immunology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.
Blood Adv. 2023 May 9;7(9):1682-1691. doi: 10.1182/bloodadvances.2022008456.
Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8-associated multicentric Castleman disease (MCD) is a polyclonal B-cell lymphoproliferative disorder that mainly occurs in immunocompromised hosts. The diagnosis relies on lymph node biopsy demonstrating KSHV-infected cells located in the mantle zone with a marked interfollicular plasma cell infiltration. Infected cells are large cells positive for immunoglobulin M (IgM), λ light chain, and CD38, described initially as infected plasmablasts. We show that IgM+λ+CD38high cells were also detectable in the peripheral blood of 14 out of 18 (78%) patients with active KSHV-MCD and absent in 40 controls. Using immunofluorescence and flow-fluorescence in situ hybridization, we demonstrate that these cells are KSHV infected and express both latent and lytic KSHV transcripts. These KSHV-infected viroblasts (KIVs) harbor a distinct phenotype compared with conventional plasmablasts. We also identified several putative mechanisms of immune escape used by KSHV, because KIVs displayed an overall decrease of costimulatory molecules, with a remarkable lack of CD40 expression and are interleukin-10-producing cells. The identification of this specific and easily accessible KSHV+ circulating population brings new elements to the understanding of KSHV-MCD but also raises new questions that need to be clarified.
卡波西肉瘤相关疱疹病毒（KSHV）/人类疱疹病毒 8 相关多中心 Castleman 病（MCD）是一种多克隆 B 细胞淋巴增生性疾病，主要发生在免疫功能低下的宿主中。诊断依赖于淋巴结活检，显示位于套区的 KSHV 感染细胞，伴有明显的滤泡间浆细胞浸润。感染细胞为大细胞，免疫球蛋白 M（IgM）、λ 轻链和 CD38 阳性，最初描述为感染的浆母细胞。我们表明，在 18 名活动性 KSHV-MCD 患者中的 14 名（78%）患者的外周血中也可检测到 IgM+λ+CD38high 细胞，而在 40 名对照中则不存在。通过免疫荧光和流式荧光原位杂交，我们证明这些细胞被 KSHV 感染，并表达潜伏和裂解的 KSHV 转录本。与传统的浆母细胞相比，这些被 KSHV 感染的病毒母细胞（KIV）具有独特的表型。我们还确定了 KSHV 用于免疫逃避的几种潜在机制，因为 KIV 显示出共刺激分子的总体减少，CD40 表达明显缺乏，并且是白细胞介素-10 产生细胞。这种特定且易于获得的 KSHV+循环群体的鉴定为理解 KSHV-MCD 带来了新的元素，但也提出了需要澄清的新问题。
