title: Advanced glycation end product-modified beta2-microglobulin is a component of amyloid fibrils of primary localized cutaneous nodular amyloidosis.
abstract: Primary localized cutaneous nodular amyloidosis is a rare form of cutaneous amyloidosis. Amyloid fibrils in primary localized cutaneous nodular amyloidosis have been reported to be originated from immunoglobulin light chains. Immunohistochemical studies on the lesional skins of four patients with primary localized cutaneous nodular amyloidosis demonstrated that amyloid deposits of all cases showed a positive reaction with the antibodies for beta2-microglobulin and advanced glycation end products as well as immunoglobulin light chain (kappa or lambda). No beta2-microglobulin and advanced glycation end product immunoreactivity was found in the amyloid deposits of other primary localized cutaneous amyloidosis (lichen amyloidosis and macular amyloidosis). Double immunofluorescence study of the lesional skin of primary localized cutaneous nodular amyloidosis showed that anti-kappa light chain, anti-beta2-microglobulin and anti-advanced glycation end product antibodies mostly reacted with the same area of amyloid deposit. Amyloid proteins were sequentially extracted with distilled water from one case of primary localized cutaneous nodular amyloidosis and recovered in the five water-soluble fractions (fractions I-V). Immunoblot assay of amyloid fibril proteins demonstrated that immunoreactive polypeptides with anti-kappa light chain antibody (29 kDa) and with anti-beta2-microglobulin antibody (12 kDa) were detected in fractions I-V, whereas immunoreactive polypeptide with anti-advanced glycation end product antibody (12 kDa) was detected exclusively in fractions III-V but not in fractions I and II. Two-dimensional polyacrylamide gel electrophoresis revealed that 12 kDa polypeptide in fractions I and II was electrophoretically identical with authentic beta2-microglobulin and that beta2-microglobulin in fractions III-V was advanced glycation end product-modified beta2-microglobulin with more acidic pI value. These results indicate that beta2-microglobulin is another major component of amyloid fibrils in primary localized cutaneous nodular amyloidosis and that beta2-microglobulin in primary localized cutaneous nodular amyloidosis is partly subjected to the modification of advanced glycation end product.
authors.affiliation: Department of Dermatology, National Defense Medical College, Saitama, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yajima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Shingo
authors.initials: S
authors.lastname: Tajima
authors.forename: Akira
authors.initials: A
authors.lastname: Ishibashi
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Hata
authors.forename: Utayo
authors.initials: U
authors.lastname: Enomoto
authors.forename: Izumi
authors.initials: I
authors.lastname: Konohana
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wachi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Seyama
mesh_terms: D000368:Aged; D000682:Amyloid / Q000502:physiology*; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D012871:Skin Diseases / Q000378:metabolism* / Q000473:pathology; D001613:beta 2-Microglobulin / Q000378:metabolism*
chemical_list: D000682:Amyloid; D017127:Glycation End Products, Advanced; D001613:beta 2-Microglobulin