Plasmacytoid Dendritic Cells Producing Interferon-α (IFN-α) and Inducing Mx1 Play an Important Role for CD4&lt;sup&gt;+ &lt;/sup&gt;Cells and CD8&lt;sup&gt;+&lt;/sup&gt; Cells in Necrotizing Lymphadenitis

Sato, Hiroko; Asano, Shigeyuki; Mori, Kikuo; Yamazaki, Kazuki; Wakasa, Haruki

doi:10.3960/jslrt.55.127

Cited by 13 publications

(22 citation statements)

References 22 publications

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“…pDCs have been associated with a variety of reactive lymph node conditions. 17,38,39 Kishimoto et al 15 first suggested increased numbers of pDCs in a small cohort of KFD patients. Pilichowska et al 16 and Rollins-Raval et al 17 described similar findings in KFD patients.…”

Section: Discussionmentioning

confidence: 99%

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Immunopathology of Kikuchi–Fujimoto disease: A reappraisal using novel immunohistochemistry markers

et al. 2020

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Aims Kikuchi–Fujimoto disease (KFD) is a self‐limited disease characterised by destruction of the lymph node parenchyma. Few studies have assessed the immunohistological features of KFD, and most employed limited antibody panels that lacked many of the novel immunohistochemistry markers currently available. Methods and results We used immunohistochemistry to reappraise the microanatomical distribution of plasmacytoid dendritic cells (pDCs), follicular helper T cells and cytotoxic T cells, B cells, follicular dendritic cell (FDC) meshworks, and histiocytes in lymph nodes involved by KFD. The study group consisted of 138 KFD patients (89 women; 64.5%) with a median age of 27 years (range, 3–50 years). Cervical lymph nodes were most commonly involved, in 108 (78.3%) patients. The numbers of pDCs were increased, predominantly around and within apoptotic areas and the paracortex, and tapering off within xanthomatous areas. pDCs formed sizeable tight clusters, most notably around apoptotic/necrotic areas. T cells consisted mostly of CD8‐positive cells with predominant expression of T‐cell receptor‐β. There were notable increases in the numbers of CD8‐positive T cells within lymphoid follicles, and their numbers correlated with alterations in FDC meshworks (P < 0.001). The number of follicular helper T cells was decreased within distorted FDC meshworks. CD21 highlighted frequent distortion of FDC meshworks, even in lymph node tissue that was distant from apoptotic/necrotic areas. Distorted FDC meshworks spanned all morphological patterns, and FDC meshwork characteristics (intact; distorted; remnant/nearly absent) correlated with morphological patterns (P < 0.01). Conclusions The immunohistological landscape of KFD is complex and characterised by increased numbers of pDCs that frequently cluster around apoptotic/necrotic foci, increased numbers of cytotoxic T cells, and substantial distortion of FDC meshworks.

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Section: Discussionmentioning

confidence: 99%

“…pDCs have been associated with a variety of reactive lymph node conditions 17,38,39 . Kishimoto et al 15 .…”

Section: Discussionmentioning

confidence: 99%

Immunopathology of Kikuchi–Fujimoto disease: A reappraisal using novel immunohistochemistry markers

et al. 2020

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“…[2][3][4] Moreover, histological specimens contained a focal necrotic area.1 Immunohistochemical study also demonstrated myeloperoxidase-positive macrophages, which is one of the characteristic immunological findings of KD. [8][9][10] However, the presence of epithelioid histiocytes and cells with plasma cell differentiation, and absence of tingible body macrophages with crescent-shaped nuclei and plasmacytoid dendritic cells in this case are different from KD. 9,10 Immunohistochemical study demonstrated mixed nature of large lymphoid cells are also different from KD.…”

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confidence: 84%

“…[8][9][10] However, the presence of epithelioid histiocytes and cells with plasma cell differentiation, and absence of tingible body macrophages with crescent-shaped nuclei and plasmacytoid dendritic cells in this case are different from KD. 9,10 Immunohistochemical study demonstrated mixed nature of large lymphoid cells are also different from KD. 1 Stanley described numerous tingible body macrophages in 2 of 10 cases by cytological examination.…”

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confidence: 84%

Infectious mononucleosis lymphadenitis resembling Kikuchi's disease: Cytological, histopathological, and immunohistological findings.

Takada

Shimizu

Nakazato

et al. 2017

J Clin Exp Hematopathol

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TO THE EDITORKikuchi's disease (KD) is a benign self-limited disease, most frequently seen in young Asians, with painless cervical lymphadenopathy and systemic symptoms such as fever. 1 The characteristic cytological findings of KD include tingible body macrophages with crescent-shaped nuclei, prominent karyorrhectic nuclei and the absence of neutrophils.2-4 The causative agents of KD remain unknown. However, Epstein-Barr virus (EBV)-encoded mRNA (EBER) was found in a few cases by in situ hybridization (ISH) 1, 5 Here, we report, here, cytological, histopathological, and immunohistochemical findings of a case of infectious mononucleosis (IM) resembling KD.A 40-year-old Japanese woman presented with bilateral cervical lymphadenopathy. A lymph node biopsy was performed and she was tentatively diagnosed with malignant lymphoma. Laboratory studies demonstrated a white blood cell count of 5.260/mm 3 with lymphocytosis of 45% including 3% atypical forms, a slightly elevated LDH level (245 <229 IU/L), and moderately abnormal liver function tests: ALT (74 <27 IU/L) and AST (125<47 IU/L). Subsequent serologic tests for EBV showed the following results: a viral capsid antigen (VCA) IgG titer of 0.2 (normal range <1), VCA IgM titer of 0.6 (normal range <0.5), and an antigen (EBNA) titer of 0.1(normal range <0.5). There was no further treatment administered, and the patient was well at the last follow-up two months later.Cytological examination of the imprint smears demonstrated a polymorphic lymphoid cell population, including numerous tingible body macrophages, and isolated or small clusters of epithelioid cells (Fig.1). No macrophages with crescent nuclei were observed in the smear. The majority of the lymphoid cells were small to medium-sized lymphocytes with scattered large transformed lymphocytes and immunoblasts (Fig.1). On Giemsa staining of a smear, the immunoblasts had round nuclei with fine nuclear chromatin, and large central nucleoli, and relatively broad basophilic cytoplasm. Some of them had a perinuclear halo (Fig. 2). Moreover, mature plasma cells, binucleated plasma cells, and cells with plasma cell differentiation were also intermingled with these cells. The epithelioid cells had an oval or elongated vesicular nuclei, and abundant amphophilic cytoplasm (Fig. 1). The lesion contained only a few neutrophils.Histologically, in a low-power field, the lesion contained a focally coagulative necrotic area (Fig. 2). Lymphoid follicles were not prominent. In a high-power field, the lesion was composed of small to medium-sized lymphocytes, large transformed lymphocytes, immunoblasts, tingible body macrophages, epithelioid cells, cells with plasma cell differentiation, and plasma cells (Fig. 5). CD3 and CD20 immunostain demonstrated the mixed natures of large transformed lymphocytes and immunoblasts. CD15 immunostain demonstrated only a few neutrophils. Scattered myeloperoxidase-positive

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“…However, it may be related to viral infection, as inferred from clinicopathological findings. [1][2][3][4][5][6][7][8] With NEL, innumerable plasmacytoid dendritic cells (PDCs) are observed in lymph nodes. The PDCs produce large quantities of interferon-α (IFN-α).…”

Section: Introductionmentioning

confidence: 99%

Necrotizing lymphadenitis may be induced by overexpression of Toll-like receptor7 (TLR7) caused by reduced TLR9 transport in plasmacytoid dendritic cells (PDCs)

Asano¹,

Sato²,

Mori³

et al. 2021

J Clin Exp Hematopathol

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Necrotizing lymphadenitis (NEL) is a self-limited systemic disease exhibiting characteristic clinical features. The pathogenesis of the disease remains unclear, but it may be associated with viral infection. In lymph nodes affected by this disease, innumerable plasmacytoid dendritic cells produce interferon-α when triggered by certain viral stimuli. IFN-α presents antigens causing the transformation of CD8 + cells into immunoblasts and apoptosis of CD4 + cells. From the perspective of innate immunity, UNC93B1, an endoplasmic reticulum (ER)-resident protein, associates more strongly with TLR9 than TLR7. Homeostasis is maintained under normal conditions. However, in NEL, TLR 7 was observed more than TLR 9, possibly because mutant type UNC93B1 associates more tightly with TLR7. The inhibitory effects against TLR7 by TLR9 were reported to disappear. It is likely that more TLR7 than TLR9 is transported from the ER to endolysosomes. In conclusion, overexpression of TLR7, an innate immune sensor of microbial single-stranded RNA, is inferred. Consequently, NEL may be induced.

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Plasmacytoid Dendritic Cells Producing Interferon-α (IFN-α) and Inducing Mx1 Play an Important Role for CD4<sup>+ </sup>Cells and CD8<sup>+</sup> Cells in Necrotizing Lymphadenitis

Cited by 13 publications

References 22 publications

Immunopathology of Kikuchi–Fujimoto disease: A reappraisal using novel immunohistochemistry markers

Immunopathology of Kikuchi–Fujimoto disease: A reappraisal using novel immunohistochemistry markers

Infectious mononucleosis lymphadenitis resembling Kikuchi's disease: Cytological, histopathological, and immunohistological findings.

Necrotizing lymphadenitis may be induced by overexpression of Toll-like receptor7 (TLR7) caused by reduced TLR9 transport in plasmacytoid dendritic cells (PDCs)

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