Review of autoantigens in Sjögren’s syndrome: an update

Abstract

Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by inflammation in exocrine glands, resulting in reduced secretion of tears and saliva, manifesting as xerophthalmia and xerostomia, respectively. It is commonly associated with Sjögren’s syndrome type A (Ro) and Sjögren’s syndrome type B (La) antigens. However, in most patients, the identity of the triggering antigen is not known. Factors such as genetics of histocompatibility, dysregulation of T-cells, B-cells and viral infections have been implicated. Several important studies on autoantigens in pSS have been published since a review in 2012, and the aim of this review is to provide an update on further peer-reviewed original articles in this field. Oxidative damage of Ro60 antigen may explain the epitope spreading during the immune activation in pSS. Immune-mediated destruction of the muscarinic receptor-3-expressing cells has been associated with a reduction in parasympathetic function, which could cause reduced secretory function of exocrine glands. Such a process also activates reactive oxidative species and antioxidants, which are linked to the triggering of inflammatory responses. Elevated levels of kallikrein, yet another antigen present in the lacrimal gland and other tissues, are similarly involved in triggering an autoimmune T-cell response against target glands. Studying additional antigens, the platelet-selectin and vasoactive intestinal peptides, in patients with pSS can help to elucidate the origin and process of autoimmunity, or even lead to potential biomarkers. In conclusion, the understanding of autoantigens has led to exciting major advances in the biology of pSS and may influence diagnosis and management of pSS in future.

Current concepts on Sjögren's syndrome – classification criteria and biomarkers

“…We published a list of potential biomarkers in 2001 and, together with recent reviews by Tong et al . and Fayyaz et al . , this should give a good overview of biomarkers that are associated with Sjögren's syndrome.…”

“…(iv) Have you had a daily feeling of dry mouth for more than 3 months? potential biomarkers in 2001 (8) and, together with recent reviews by TONG et al (9) and FAYYAZ et al (10), this should give a good overview of biomarkers that are associated with Sj€ ogren's syndrome. Autoantibodies to the autoantigens Ro/SSA and La/ SSB are the most important biomarkers identified to date and have been incorporated into the classification criteria for primary Sj€ ogren's syndrome (5,(11)(12)(13)(14).…”

Respiratory virus-induced heterologous immunity

“…Viral infections, including CV have been suggested to play a role in the development of SS [131]. In SS, antibodies and/or T cells to different autoantigens, frequently Ro (SSA) and La (SSB) are present [132,133]. Sequence homologies between the 2B protein of CV A21/A13 and the Ro60 kDa antigen may induce crossreactive autoantibodies.…”

Respiratory virus-induced heterologous immunity

“…Pre-existing HA 391-410 -speci c CD4 + T m cells showed expansion a er seasonal IV vaccination. ese T m cells expanded a er stimulation with the Trichomonas vaginalis (T. vaginalis)-derived hypothetical protein [118][119][120][121][122][123][124][125][126][127][128][129][130] -and the Finegoldia magna (F. magna)derived hypothetical protein [131][132][133][134][135][136][137][138][139][140][141][142][143] peptide in vitro (Tab. 1).…”

“…Viral infections, including CV have been suggested to play a role in the development of SS [131]. In SS, antibodies and/or T cells to di erent autoantigens, frequently Ro (SSA) and La (SSB) are present [132,133]. Sequence homologies between the 2B protein of CV A21/A13 and the Ro60 kDa antigen may induce cross-reactive autoantibodies.…”