Immunity to extracellular matrix antigens is associated with ultrastructural alterations of the stroma and stratified epithelium basement membrane in the skin of Hashimoto's thyroiditis patients

Employing purified extracellular matrix (ECM) proteins, i.e. type I, III, IV and V collagens (Cl, 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 Hashimoto's 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=4x10(-9)). Reactivity to conformational antigens, mostly due to autoantibodies of the IgG isotype, was observed in 30150 HT sera and in 6/51 control sera (p=3.5x10(-7)) and was not always concomitant with that to linear antigens, found in 23/50 HT and in 6/51 control sera (p=1.6x10(-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.