Inflammation and Epstein-Barr Virus Infection Are Common Features of Myasthenia Gravis Thymus: Possible Roles in Pathogenesis
Immunohistochemistry for latent LMP1 (a)–(h) and lytic BZLF1 (i)–(p) EBV proteins. (a) to (h) LMP1 immunostaining. No signal of immunoreactivity was observed in negative control performed by incubating sections with isotype-specific nonimmune IgG (Dako) (a). LMP1 was not detected in EBV-negative Jurkat T-cell line (b) but was readily detectable in EBV-positive JY cells (c). Normal thymuses showed no immunoreactivity for LMP1 antibody (d). In hyperplastic thymuses (MG1 is shown), LMP1+ cells were detected in areas containing CD20+ B cells organized in germinal centers (GCs) ((e) and inset in (e)) or were diffused throughout the highly infiltrated medullary region (f). Numerous LMP1+ cells were identified in thymitis cases (MG13 is shown), that were diffused in thymic medulla and frequently located around Hassall’s corpuscles (HCs), where often concentrate B cells (g). In involuted thymuses (MG16 is shown), numerous LMP1+ cells were scattered in the residual thymic parenchyma and frequently located in thymic infiltrated areas around HCs (h). Inset in (e) shows CD20 immunostaining of the same area of the main panel in a serial section. Insets in (f), (g), and (h) show areas of the main panels at higher power of magnification to reveal membrane localization of LMP1. (i) to (p) BZLF1 immunostaining. No signal of immunoreactivity was observed in negative control performed by incubating sections with isotype-specific nonimmune IgG (Dako) (i). BZLF1 was not detected in EBV-negative Jurkat T-cell line (j) but was readily detectable in EBV-positive JY cells (k). Normal thymuses showed no immunoreactivity for BZLF1 antibody (l). In hyperplasia (MG1 is shown), BZLF1+ cells were often detected at the edge of GCs ((m) and inset in (m)) or were scattered in thymic medulla (n). Inset in (m) shows CD20 immunostaining of the same area of the main panel in a serial section. In thymitis (MG11 is shown) (o) and involuted thymuses (MG17 is shown) (p), BZLF1+ cells were present in thymic medulla, in some cases located within medullary infiltrates in proximity to HCs. Magnifications: ×20 (a, d, i, l); ×40 (b, c, e, f, g, h, j, k, m, o, p); ×80 (n).
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