EBV and other viruses as triggers of tertiary lymphoid structures in primary Sjögren's syndrome.

[Ecoclimber]

Expert Rev Clin Immunol. 2014 Feb 25. [Epub ahead of print]
EBV and other viruses as triggers of tertiary lymphoid structures in primary Sjögren's syndrome.
Lucchesi D1, Pitzalis C, Bombardieri M.
Author information
Abstract
Sjogren's syndrome (SS) is an autoimmune disease that targets salivary (SG) and lachrymal glands, leading to exocrine dysfunction. Several viruses have been associated with SS, although the role of persistent viral infections in triggering and/or perpetuating the disease is still a matter of controversy. ]

Together with exocrine dysfunction, SS is characterised by the production of autoantibodies and the presence of lymphomonocytic periductal aggregates in the SG, which in 30/40% of the patients display features of tertiary lymphoid structures (TLS) supporting an ectopic germinal centre response.

Here we first review i) the relevance of TLS in SS and ii) the evidence in support of a role for viruses in SS insurgence and/or persistence; next, iii) we review recent data which links viral infection with TLS formation in the SG and suggests that viral-host interactions within TLS favour breach of tolerance and development of autoimmunity in SS.

 

[pattismith]

interesting study about vaccination of Sjogren patients with no concurrent immune suppressive treatment

H1N1 vaccination in Sjögren’s syndrome triggers polyclonal B cell activation and promotes autoantibody production 2017

doi: 10.1136/annrheumdis-2016-210509
Results
Surprisingly, treatment-naïve patients with Sjögren’s syndrome developed higher H1N1 IgG titres of greater avidity than healthy controls on vaccination.

Notably, off-target B cells were also triggered resulting in increased anti-EBV and autoantibody titres.

Endosomal toll-like receptor activation of naïve B cells in vitro revealed a greater propensity of patient-derived cells to differentiate into plasmablasts and higher production of class switched IgG.

The amplified plasma cell differentiation and class switch could be induced in cells from healthy donors by preincubation with type 1 interferon, but was abolished in hydroxychloroquine-treated patients and after in vitro exposure of naïve B cells to chloroquine.

Conclusions
This comprehensive analysis of the immune response in autoimmune patients to exogenous stimulation identifies a mechanistic basis for the B cell hyperactivity in Sjögren’s syndrome, and suggests that caution is warranted when considering vaccination in non-treated autoimmune patients.

Participants and vaccination procedure

Female patients with pSS fulfilling the American-European consensus critera7 and positive for anti-Ro/SSA and/or anti-La/SSB autoantibodies (n=14) and matched healthy controls (n=18) (supplementary table S1) were vaccinated twice with the squalene-adjuvanted inactivated split-virion H1N1 vaccine Pandemrix (GlaxoSmithKline, Brentford, UK). Blood sampling and collection of clinical parameters was performed prior to, and 1 and 3 weeks after each vaccination.