Article Text

PDF
SAT0377 Interferon Gamma-Inducible Protein 16 (IFI16) in Primary SjÖgren's Syndrome: A Novel Player in Disease Pathogenesis?
  1. A. Alunno1,
  2. V. Caneparo2,
  3. F. Carubbi3,
  4. O. Bistoni1,
  5. S. Caterbi1,
  6. E. Bartoloni1,
  7. R. Giacomelli3,
  8. M. Gariglio2,
  9. S. Landolfo4,
  10. R. Gerli1
  1. 1Department of Medicine, Rheumatology Unit, University of Perugia, Perugia
  2. 2Department of Translational Medicine, Virology Unit, Novara Medical School, Novara
  3. 3Department of Biotechnological and Applied Clinical Sciences, Rheumatology Unit, University of L'Aquila, L'Aquila
  4. 4Department of Public Health and Pediatric Sciences, Viral Pathogenesis Unit, Turin Medical School, Turin, Italy

Abstract

Background Although the pathogenesis of primary Sjögren's syndrome (pSS) is not fully elucidated, several studies suggest that the interferon (IFN) signature is involved in both induction and perpetuation of the disease (1). The interferon gamma-inducible protein 16 (IFI16), normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders, including systemic lupus erythematosus and systemic sclerosis. This leads to tolerance breaking to this self-protein with consequent development of anti-IFI16 autoantibodies (2-4).

Objectives Aim of the present study was to investigate the possible pathogenic and/or clinical significance of IFI16 and anti-IFI16 antibodies in pSS.

Methods Sixty-seven female patients with pSS were evaluated and 182 healthy donors (HD) acted as controls. IFI16 and anti-IFI16 concentrations were assessed in serum samples with ELISA. IFI16 was also evaluated in 10 pSS minor salivary glands (MSGs). MSGs of sicca-non pSS subjects displaying either normal architecture or non-specific chronic sialadenitis (NSCS) acted as controls. Hematoxilin and eosin staining and CD3/CD20 double immunofluorescence were performed in serial sections to grade all MSGs and to assess B/T cell compartmentalization respectively.

Results IFI16 was not constitutively expressed in normal MSGs. In NSCS-MSGs, IFI16 was expressed by glandular epithelium, endothelial cells and some of infiltrating lymphocytes, but not by plasma cells. pSS-MSGs displayed marked expression and cytoplasmic mislocalization of IFI16 by acinar and ductal epithelial cells as well as infiltrating lymphocytes and peri/intra-lesional endothelium compared to MSGs with normal architecture or NSCS. Within the mononuclear cell infiltrate, IFI16 distribution in mononuclear cell infiltrates overlapped that of T lymphocytes appearing nicely compartmentalized in those pSS-MSGs displaying B/T cell segregation.

pSS patients displayed higher concentration of IFI16 protein and higher titer of anti-IFI16 antibodies in the serum compared to HD. Serum IFI16 concentration was directly correlated with disease duration and focus score and inversely correlated with the age at diagnosis. IFI16 protein positivity in the serum was associated with concurrent positivity for rheumatoid factor. Of interest, the direct correlation between IFI16 positivity and the focus score was independent of disease duration and age at diagnosis. No correlations between anti-IFI16 antibodies and any clinical and/or serological parameters were identified

Conclusions The overexpression and cytoplasmic mislocalization of IFI16 protein at glandular level, the occurrence of free IFI16 protein in the serum and the detection of specific circulating autoantibodies in pSS, may suggest a link between this autoantigen and pSS pathogenesis. Larger and prospective studies are required to shed additional light on the pathogenic mechanisms mediated by IFI16 as well as on a possible application of serum IFI16 protein detection in clinical practice.

References

  1. Nguyen CQ et al. Front Immunol 2013;4:142

  2. Costa S et al. Br J Dermatol 2011; 164: 282–290

  3. Costa S et al. Rheumatology (Oxford) 2011;50:674-681

  4. Caneparo V et al. Lupus 2013;22:607-613

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.