title: C-type lectin domain family 12, member A: A common denominator in Behçet's syndrome and acute gouty arthritis.
abstract: C-type lectin domain family 12, member A (CLEC12A) is a C-type lectin-like pattern recognition receptor capable of recognizing monosodium urate crystals. Monosodium urate crystals, the causative agents of gout are also among the danger-associated molecular patterns reflecting cellular injury/cell death. In response to monosodium urate crystals, CLEC12A effectively inhibits granulocyte and monocyte/macrophage functions and hence acts as a negative regulator of inflammation. Behçet's syndrome and gout are autoinflammatory disorders sharing certain pathological (neutrophilic inflammation), clinical (exaggerated response to monosodium urate crystals) and therapeutic (colchicine) features. We propose the hypothesis that decreased expression of CLEC12A is a common denominator in the hyperinflammatory responses observed in Behçet's syndrome and gout. Major lines of evidence supporting this hypothesis are: (1) Downregulation/deficiency of CLEC12A is associated with hyperinflammatory responses. (2) CLEC12A polymorphisms with functional and clinical implications have been documented in other inflammatory diseases. (3) Colchicine, a fundamental therapeutic agent used both in Behçet's syndrome and gout is shown to oppose the downregulation of CLEC12A. (4) Behçet's syndrome and gout are characterized by a hyperinflammatory response to monosodium urate crystals and other than gout, Behçet's syndrome is the only inflammatory condition exhibiting this exaggerated response. (5) Genomewide linkage and association studies of Behçet's syndrome collectively point to 12p12-13, the chromosomal region harboring CLEC12A. (6) Patients with severe forms of Behçet's syndrome underexpress CLEC12A with respect to patients with mild forms of the disease. If supported by well-designed, rigorous experiments, the forementioned hypothesis pertinent to CLEC12A will carry important implications for therapy, designing experimental models, and uncovering immunopathogenic mechanisms in Behçet's syndrome and gout.
authors.affiliation: Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey; Biotechnology Institute, Ankara University, Ankara, Turkey. Electronic address: drakoguz@gmail.com.
authors.forename: Ali Kemal
authors.initials: AK
authors.lastname: Oğuz
authors.affiliation: Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey; Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Seda
authors.initials: S
authors.lastname: Yılmaz
authors.affiliation: Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey; Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Nejat
authors.initials: N
authors.lastname: Akar
authors.affiliation: Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey; Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Hilal
authors.initials: H
authors.lastname: Özdağ
authors.affiliation: Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey; Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Aysel
authors.initials: A
authors.lastname: Gürler
authors.affiliation: Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey; Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Aşkın
authors.initials: A
authors.lastname: Ateş
authors.affiliation: Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey; Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Çağdaş Şahap
authors.initials: ÇŞ
authors.lastname: Oygür
authors.affiliation: Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey; Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Sibel Serin
authors.initials: SS
authors.lastname: Kılıçoğlu
authors.affiliation: Department of Internal Medicine, Ufuk University School of Medicine, Ankara, Turkey; Biotechnology Institute, Ankara University, Ankara, Turkey.
authors.forename: Selda
authors.initials: S
authors.lastname: Demirtaş
mesh_terms: D000208:Acute Disease; D015210:Arthritis, Gouty / Q000276:immunology*; D001528:Behcet Syndrome / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology*; D018448:Models, Immunological; D011975:Receptors, Mitogen / Q000276:immunology*; D014527:Uric Acid / Q000276:immunology*
chemical_list: C485220:CLEC12A protein, human; D007155:Immunologic Factors; D037181:Lectins, C-Type; D011975:Receptors, Mitogen; D014527:Uric Acid