title: Immunity to extracellular matrix antigens is associated with ultrastructural alterations of the stroma and stratified epithelium basement membrane in the skin of Hashimotos thyroiditis patients.
abstract: Employing purified extracellular matrix (ECM) proteins, i.e. type I, III, IV and V collagens (CI, CIII, CIV, CV), laminin (LM) and fibronectin (FN), as antigen sources we detected autoantibodies to conformational and/or denatured ECM antigens among 34 of 50 sera obtained from Hashimotos thyroiditis (HT) patients and 6 of 51 control sera obtained from non-autoimmune thyroid disease patients and healthy donors (HT sera vs. control sera p=4 x 10-9). Reactivity to conformational antigens, mostly due to autoantibodies of the IgG isotype, was observed in 30/50 HT sera and in 6/51 control sera (p=3.5 x 10-7) and was not always concomitant with that to linear antigens, found in 23/50 HT and in 6/51 control sera (p=1.6 x 10-4). Ultrastructural analysis of skin biopsies obtained from 18 HT patients without symptomatic cutaneous diseases revealed defects of the stratified squamous epithelium basement membrane in 11/18, alterations of the stroma in 13/18 and both basement membrane and stromal defects in 9/18. Interestingly, 13/13 (p=0.012) and 9/11 (p=0.012) patients with stromal and basement membrane defects respectively, exhibited serum antibodies to at least one ECM antigen involved in the organization of the altered tissue compartment. Lastly, 10/18 skin biopsies presented immunoglobulin (Ig) and/or complement (C3) deposits along the cutaneous basement membrane zone (BMZ) or in the papillary dermis and 9/10 sera from the same patients simultaneously showed antibodies to at least one ECM antigen involved in the organization of these two skin compartments. Besides, 8/11 HT patients with basement membrane defects exhibited Ig or C3 deposits along the BMZ. Our findings suggest that autoantibodies to ECM molecules might contribute to the development of asymptomatic extra-thyroid skin diseases in HT patients.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University, Tor Vergata, Rome, Italy. bei@med.uniroma2.it
authors.forename: R
authors.initials: R
authors.lastname: Bei
authors.forename: D
authors.initials: D
authors.lastname: Mentuccia
authors.forename: P
authors.initials: P
authors.lastname: Trono
authors.forename: P
authors.initials: P
authors.lastname: Trono
authors.forename: L
authors.initials: L
authors.lastname: Masuelli
authors.forename: V
authors.initials: V
authors.lastname: Cereda
authors.forename: C
authors.initials: C
authors.lastname: Palumbo
authors.forename: L
authors.initials: L
authors.lastname: Marzocchella
authors.forename: M A
authors.initials: MA
authors.lastname: Mrozek
authors.forename: P
authors.initials: P
authors.lastname: Pallotta
authors.forename: G
authors.initials: G
authors.lastname: Di Lella
authors.forename: M
authors.initials: M
authors.lastname: Modesti
authors.forename: M
authors.initials: M
authors.lastname: Cerilli
authors.forename: G V
authors.initials: GV
authors.lastname: Frajese
authors.forename: G
authors.initials: G
authors.lastname: Frajese
authors.forename: G
authors.initials: G
authors.lastname: Zambruno
authors.forename: A
authors.initials: A
authors.lastname: Modesti
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D001485:Basement Membrane / Q000648:ultrastructure; D003176:Complement C3 / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000276:immunology*; D050031:Hashimoto Disease / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood; D007136:Immunoglobulins / Q000032:analysis; D012867:Skin / Q000648:ultrastructure*; D017154:Stromal Cells / Q000648:ultrastructure
chemical_list: D001323:Autoantibodies; D003176:Complement C3; D016326:Extracellular Matrix Proteins; D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins