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Interferon gamma-inducible protein 16 in primary Sjögren's syndrome: a novel player in disease pathogenesis?

Alunno A, Caneparo V, Carubbi F, Bistoni O, Caterbi S, Bartoloni E, Giacomelli R, Gariglio M, Landolfo S, Gerli R - Arthritis Res. Ther. (2015)

Bottom Line: Moreover, IFI16 positivity was associated with concurrent positivity for rheumatoid factor.Interestingly, the direct correlation between IFI16 positivity and focus score was independent of disease duration and age at diagnosis. pSS minor salivary glands display marked expression and cytoplasmic mislocalization of IFI16 by acinar and ductal epithelial cells as well as infiltrating lymphocytes and peri/intralesional endothelium compared to minor salivary glands with normal architecture or nonspecific chronic sialadenitis.Within the mononuclear cell infiltrate, IFI16 expression appears to parallel the distribution of T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy. alessia.alunno@libero.it.

ABSTRACT

Introduction: There is evidence that interferon is involved in the pathogenesis of primary Sjögren's syndrome (pSS). The interferon-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders. This leads to tolerance breaking to this self-protein with consequent development of anti-IFI16 antibodies. The aim of this study was to identify the pathogenic and clinical significance of IFI16 and anti-IFI16 in pSS.

Methods: IFI16 and anti-IFI16 were assessed in the serum of 67 pSS patients and over 100 healthy donors by enzyme-linked immunosorbent assay. IFI16 was also evaluated by immunohistochemistry in minor salivary glands of 15 pSS patients and 10 subjects with sicca symptoms but without any clinical, serological or histological features of pSS.

Results: pSS patients display higher serum levels of both IFI16 and anti-IFI16 compared to healthy donors. IFI16 concentration was directly correlated with disease duration and focus score and inversely correlated with age at diagnosis. Moreover, IFI16 positivity was associated with concurrent positivity for rheumatoid factor. Interestingly, the direct correlation between IFI16 positivity and focus score was independent of disease duration and age at diagnosis. pSS minor salivary glands display marked expression and cytoplasmic mislocalization of IFI16 by acinar and ductal epithelial cells as well as infiltrating lymphocytes and peri/intralesional endothelium compared to minor salivary glands with normal architecture or nonspecific chronic sialadenitis. Within the mononuclear cell infiltrate, IFI16 expression appears to parallel the distribution of T lymphocytes.

Conclusion: Our data suggest that the IFI16 protein may be involved in the pathogenesis of glandular inflammation occurring in pSS.

No MeSH data available.


Related in: MedlinePlus

Expression of interferon gamma-inducible (IFI16) protein (a) and anti-IFI16 antibodies (b) in healthy donors (HD; n = 116 and n = 182, respectively) and primary Sjögren’s syndrome (pSS) patients (n = 67). Bars indicate mean values. Dotted lines mark cut-off levels of positivity determined as the 95th percentile of the control population. p values were calculated with Mann Whitney U test
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Fig1: Expression of interferon gamma-inducible (IFI16) protein (a) and anti-IFI16 antibodies (b) in healthy donors (HD; n = 116 and n = 182, respectively) and primary Sjögren’s syndrome (pSS) patients (n = 67). Bars indicate mean values. Dotted lines mark cut-off levels of positivity determined as the 95th percentile of the control population. p values were calculated with Mann Whitney U test

Mentions: As shown in Fig. 1, serum levels of both IFI16 protein and anti-IFI16 antibodies were higher in pSS than in HDs (p < 0.05 and p < 0.0001, respectively). According to a cut-off established as the 95th percentile of the control population, positivity for IFI16 protein and for anti-IFI16 was considered for values ≥27 ng/ml and ≥113 U/ml, respectively. IFI16 was significantly more prevalent in pSS compared to HDs as it was detectable in 14/67 patients (21 %) and in 6/116 HDs (5 %) (p < 0.0001). Similarly, a significantly higher prevalence in pSS was confirmed also for anti-IFI16 antibodies that were present in 23/67 pSS patients (34 %) and in 9/182 HDs (5 %) (p < 0.0001).Fig. 1


Interferon gamma-inducible protein 16 in primary Sjögren's syndrome: a novel player in disease pathogenesis?

Alunno A, Caneparo V, Carubbi F, Bistoni O, Caterbi S, Bartoloni E, Giacomelli R, Gariglio M, Landolfo S, Gerli R - Arthritis Res. Ther. (2015)

Expression of interferon gamma-inducible (IFI16) protein (a) and anti-IFI16 antibodies (b) in healthy donors (HD; n = 116 and n = 182, respectively) and primary Sjögren’s syndrome (pSS) patients (n = 67). Bars indicate mean values. Dotted lines mark cut-off levels of positivity determined as the 95th percentile of the control population. p values were calculated with Mann Whitney U test
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4536589&req=5

Fig1: Expression of interferon gamma-inducible (IFI16) protein (a) and anti-IFI16 antibodies (b) in healthy donors (HD; n = 116 and n = 182, respectively) and primary Sjögren’s syndrome (pSS) patients (n = 67). Bars indicate mean values. Dotted lines mark cut-off levels of positivity determined as the 95th percentile of the control population. p values were calculated with Mann Whitney U test
Mentions: As shown in Fig. 1, serum levels of both IFI16 protein and anti-IFI16 antibodies were higher in pSS than in HDs (p < 0.05 and p < 0.0001, respectively). According to a cut-off established as the 95th percentile of the control population, positivity for IFI16 protein and for anti-IFI16 was considered for values ≥27 ng/ml and ≥113 U/ml, respectively. IFI16 was significantly more prevalent in pSS compared to HDs as it was detectable in 14/67 patients (21 %) and in 6/116 HDs (5 %) (p < 0.0001). Similarly, a significantly higher prevalence in pSS was confirmed also for anti-IFI16 antibodies that were present in 23/67 pSS patients (34 %) and in 9/182 HDs (5 %) (p < 0.0001).Fig. 1

Bottom Line: Moreover, IFI16 positivity was associated with concurrent positivity for rheumatoid factor.Interestingly, the direct correlation between IFI16 positivity and focus score was independent of disease duration and age at diagnosis. pSS minor salivary glands display marked expression and cytoplasmic mislocalization of IFI16 by acinar and ductal epithelial cells as well as infiltrating lymphocytes and peri/intralesional endothelium compared to minor salivary glands with normal architecture or nonspecific chronic sialadenitis.Within the mononuclear cell infiltrate, IFI16 expression appears to parallel the distribution of T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy. alessia.alunno@libero.it.

ABSTRACT

Introduction: There is evidence that interferon is involved in the pathogenesis of primary Sjögren's syndrome (pSS). The interferon-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders. This leads to tolerance breaking to this self-protein with consequent development of anti-IFI16 antibodies. The aim of this study was to identify the pathogenic and clinical significance of IFI16 and anti-IFI16 in pSS.

Methods: IFI16 and anti-IFI16 were assessed in the serum of 67 pSS patients and over 100 healthy donors by enzyme-linked immunosorbent assay. IFI16 was also evaluated by immunohistochemistry in minor salivary glands of 15 pSS patients and 10 subjects with sicca symptoms but without any clinical, serological or histological features of pSS.

Results: pSS patients display higher serum levels of both IFI16 and anti-IFI16 compared to healthy donors. IFI16 concentration was directly correlated with disease duration and focus score and inversely correlated with age at diagnosis. Moreover, IFI16 positivity was associated with concurrent positivity for rheumatoid factor. Interestingly, the direct correlation between IFI16 positivity and focus score was independent of disease duration and age at diagnosis. pSS minor salivary glands display marked expression and cytoplasmic mislocalization of IFI16 by acinar and ductal epithelial cells as well as infiltrating lymphocytes and peri/intralesional endothelium compared to minor salivary glands with normal architecture or nonspecific chronic sialadenitis. Within the mononuclear cell infiltrate, IFI16 expression appears to parallel the distribution of T lymphocytes.

Conclusion: Our data suggest that the IFI16 protein may be involved in the pathogenesis of glandular inflammation occurring in pSS.

No MeSH data available.


Related in: MedlinePlus