Degree of lymphoid organization of the periductal lymphocytic infiltrates in salivary gland of patients with Sjögren's syndrome (SS)

<p><b>Copyright information:</b></p><p>Taken from "Increased circulating levels and salivary gland expression of interleukin-18 in patients with Sjögren's syndrome: relationship with autoantibody production and lymphoid organization of the periductal inflammatory infiltrate"</p><p>Arthritis Research & Therapy 2004;6(5):R447-R456.</p><p>Published online 3 Aug 2004</p><p>PMCID:PMC546280.</p><p>Copyright © 2004 Bombardieri et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.</p> Paraffin-embedded sections were double-stained for CD3 (brown) and CD20 (purple) (a–c) and single-stained with CD21 (d). Inflammatory foci were classified as nonsegregated when T and B lymphocytes were not compartmentalized in distinct areas (a), as segregated in the presence of evident compartmentalization of T and B cells (b), and as segregated with germinal-centre-like structures (arrow) when a clear histological appearance (c) and networks of CD21follicular dendritic cells (d) were observed. Original magnification × 200

Immunohistochemical (IHC) detection of IL-18 in salivary glands of patients with Sjögren's syndrome (SS) and in nonspecific chronic sialoadenitis

<p><b>Copyright information:</b></p><p>Taken from "Increased circulating levels and salivary gland expression of interleukin-18 in patients with Sjögren's syndrome: relationship with autoantibody production and lymphoid organization of the periductal inflammatory infiltrate"</p><p>Arthritis Research & Therapy 2004;6(5):R447-R456.</p><p>Published online 3 Aug 2004</p><p>PMCID:PMC546280.</p><p>Copyright © 2004 Bombardieri et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.</p> (a,b) Paraffin-embedded section of glands in SS, showing high amounts of IL-18-expressing cells distributed in a scattered fashion within the periductal mononuclear infiltrate. (c) IL-18-positive cells were also observed surrounding acini (arrows) in proximity with the inflammatory aggregate. (d–f) Paraffin-embedded sections of glands from patients with nonspecific chronic sialoadenitis, demonstrating the absence of IL-18 expression in mononuclear cells in nonfocal periductal infiltrates. (g) Paraffin-embedded sections of glands from patients with SS, double-stained for CD68 (brown) and IL-18 (purple), showed exclusive co-localization of IL-18 expression in most of the CD68macrophages (arrows) within the periductal inflammatory infiltrates. (h) Macrophages expressing a large amount of IL-18 (arrows) were also observed surrounding acini in contiguity with a focal lymphocytic aggregate. (i, same sample as g) Conversely, CD68macrophages adjacent to a nonfocal infiltrate remained single-stained. Original magnification (a,b,d) × 100, (c,e–i) × 200

Relationship between IL-18 expression and B-/T-cell compartmentalization and germinal-center-like (GC-like) structures in the salivary glands of patient with Sjögren's syndrome (SS) and, for comparison, in normal lymph nodes

<p><b>Copyright information:</b></p><p>Taken from "Increased circulating levels and salivary gland expression of interleukin-18 in patients with Sjögren's syndrome: relationship with autoantibody production and lymphoid organization of the periductal inflammatory infiltrate"</p><p>Arthritis Research & Therapy 2004;6(5):R447-R456.</p><p>Published online 3 Aug 2004</p><p>PMCID:PMC546280.</p><p>Copyright © 2004 Bombardieri et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.</p> Representative section of a large segregated aggregate double-stained for CD20 (brown) and IL-18 (purple) (a), and (b) sequential section with an irrelevant antibody replacing the anti-CD20, demonstrating the presence of IL-18-producing cells both in the T-cell (a, arrows) and B-cell (b, arrows) areas. (c) Single staining for IL-18, demonstrating a large number of IL-18-producing cells within ectopic GC-like structures in salivary gland from SS. (d) Double immunohistochemical staining for CD68 (brown) and IL-18 (purple), demonstrating the exclusive co-localization of IL-18 with CD68 macrophages. (e–h) An identical pattern of distribution in terms of IL-18 expression and co-localization with CD68 macrophages was observed in GCs of secondary lymphoid organs. Histomorphological analysis of the IL-18 positive cells within the GC showed evidence of engulfed apoptotic bodies in the cytoplasm (e) that identifies these cells as tingible body macrophages (TBMs). (f) Double immunohistochemical staining for CD68/IL-18 confirmed the exclusive co-localization of IL-18 with TBMs within the GC. Sequential sections in which the anti-CD68 (e), anti-IL-18 (g), or both the primary antibodies (h) were replaced with an isotype-matched irrelevant antibody confirmed the specificity of the double staining (h, negative control). Original magnification (a–d) × 200, (e-h) × 40

IL-18 expression in salivary gland ducts of patients with Sjögren's syndrome (SS) and nonspecific chronic sialoadenitis

<p><b>Copyright information:</b></p><p>Taken from "Increased circulating levels and salivary gland expression of interleukin-18 in patients with Sjögren's syndrome: relationship with autoantibody production and lymphoid organization of the periductal inflammatory infiltrate"</p><p>Arthritis Research & Therapy 2004;6(5):R447-R456.</p><p>Published online 3 Aug 2004</p><p>PMCID:PMC546280.</p><p>Copyright © 2004 Bombardieri et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.</p> IL-18-positive ducts were detected in all the SS samples but in only a minority of those from chronic sialoadenitis. A considerable range of variability of IL-18 expression was observed in ducts among different samples. Within the same glandular lobule, positive and negative (arrowheads) adjacent ducts were observed (a). Ductal IL-18 expression was found in ducts surrounded (b) and not surrounded (c) by focal infiltrate, as well as in ducts characterized by periductal fibrosis (d). In contrast to ductal epithelial cells, no staining for IL-18 was found in acinar cells (a,d, stars). In a minority of patients with chronic sialoadenitis, we observed similar ductal staining patterns. Representative examples of positive (e) and negative (f) ductal IL-18 staining in different patients with chronic sialoadenitis are shown. Original magnification × 200