title: Mechanisms of crystal formation in gout-a structural approach.
abstract: The mechanisms and sites of monosodium urate monohydrate (MSU) crystal deposition in gout have received little attention from the scientific community to date. Formalin fixation of tissues leads to the dissolution of MSU crystals, resulting in their absence from routinely processed pathological samples and hence neglect. However, modern imaging techniques-especially ultrasonography but also conventional CT and dual-energy CT-reveal that MSU crystals form at the cartilage surface as well as inside tendons and ligaments, often at insertion sites. Tophi comprise round white formations of different sizes surrounded by inflammatory tissue. Studies of fibres recovered from gouty synovial fluid indicate that these fibres are likely to be a primary site of crystal formation by templated nucleation, with crystals deposited parallel to the fibres forming transverse bands. In tophi, two areas can be distinguished: one where crystals are formed on cellular tissues and another consisting predominantly of crystals, where secondary nucleation seems to take place; this organization could explain how tophi can grow rapidly. From these observations based on a crystallographic approach, it seems that initial templated nucleation on structural fibres-probably collagen-followed at some sites by secondary nucleation could explain MSU crystal deposition in gout.
authors.affiliation: Department of Medicine, Rheumatology Section, Hospital General Universitario de Alicante, Universidad Miguel Hernández, Pintor Baeza 12, Alicante 03010, Spain.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Pascual
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, 234 Herzl Street, Rehovot 7610001, Israel.
authors.forename: Lia
authors.initials: L
authors.lastname: Addadi
authors.affiliation: Department of Medicine, Rheumatology Section, Hospital General Universitario de Alicante, Universidad Miguel Hernández, Pintor Baeza 12, Alicante 03010, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Andrés
authors.affiliation: Rheumatology Unit, Hospital General Universitario de Elda, Carretera Elda-Sax SN, Elda 03600, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Sivera
mesh_terms: D003460:Crystallization; D006073:Gout / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D014527:Uric Acid / Q000378:metabolism
chemical_list: D014527:Uric Acid