Ductal epithelial expression of Ro52 correlates with inflammation in salivary glands of patients with primary Sjögren's syndrome

Aqrawi, Lara A.; Kvarnström, Marika; Brokstad, Karl Albert; Jönsson, Roland; Skarstein, Kathrine; Wahren‐Herlenius, Marie

doi:10.1111/cei.12341

Cited by 28 publications

(17 citation statements)

References 41 publications

(57 reference statements)

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“…Similar increased expression of Ro-52 has been reported in salivary ductal epithelium as well, and the level of expression tallied with the degree of inflammation [59]. Further evidence for Ro-52 in autoimmunity comes from two Ro-52 deficient mice models [54,60].…”

Section: Introductionsupporting

confidence: 57%

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Update on Pathogenesis of Sjogren's Syndrome

Sandhya¹,

Kurien²,

Danda³

et al. 2017

CRR

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Sjögren’s syndrome is a common autoimmune disease that presents with sicca symptoms and extraglandular features. Sjögren’s syndrome is presumably as common as RA; yet it is poorly understood, underdiagnosed and undertreated. From the usual identity as an autoimmune exocrinopathy to its most recent designate as an autoimmune epithelitis – the journey of SS is complex. We herein review some of the most important milestones that have shed light on different aspects of pathogenesis of this enigmatic disease. This includes role of salivary gland epithelial cells, and their interaction with cells of innate and adaptive immune system. Non-immune factors acting in concert or in parallel with immune factors may also be important. The risk genes identified so far have only weak association, nevertheless advances in genetics have enhanced understanding of disease mechanisms. Role of epigenetic and environmental factors are also being explored. SS also has some unique features such as congenital heart block and high incidence of lymphoma; disease mechanisms accounting for these manifestations are also reviewed.

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Section: Introductionsupporting

confidence: 57%

“…Increased Ro and La expression has been demonstrated in MSG of patients with SS as compared with controls [59,66]. Also those with higher La expression were detected to have higher anti-La antibody implicating antigen driven autoantibody response [67].…”

Section: Introductionmentioning

confidence: 99%

Update on Pathogenesis of Sjogren's Syndrome

Sandhya¹,

Kurien²,

Danda³

et al. 2017

CRR

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“…26 27 Inflammatory conditions in SG of patients with pSS have been shown to induce ductal expression of Ro52. 28 In addition, expression and location of Ro52 in different cellular compartments have been modulated by activation of innate immunity through toll-like receptor 3 (TLR3), interferon-alpha (IFN-α) and nitric oxide. [29][30][31] In NZM2758 mice, we observed that alum treatment caused significant upregulation of circulating KC, IL-1α, MIG, MIP2 and PDGF-β (see online supplementary figure S5).…”

Section: Discussionmentioning

confidence: 99%

Interaction between innate immunity and Ro52-induced antibody causes Sjögren's syndrome-like disorder in mice

et al. 2015

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Objectives Autoantibodies reactive with Ro52 are often found in sera of Sjögren’s syndrome (SS) patients. This study was undertaken to investigate the role of Ro52-induced immune responses in pathogenesis of SS. Methods New Zealand Mixed (NZM) 2758 mice were immunized with Ro52 in alum adjuvant. Control mice were immunized either with Maltose binding protein (MBP) or injected with alum alone. Mice were monitored for anti-Ro52 antibody, sialoadenitis and pilocarpine induced salivation. Antibody binding to salivary gland (SG) cells was analyzed in vivo and in vitro by immunofluorescence. Sera from immunized mice were passively transferred into untreated or alum injected NZM2758 mice. Results By day 30 post-immunization, Ro52 immunized mice generated immunoprecipitating anti-Ro52 antibodies and they had the maximum drop in saliva production. Both Ro52 immunized and control mice showed evidence of mild sialoadenitis. However, only Ro52 immunized mice had antibody deposition in their SG. Passive transfer of Ro52-immune sera induced SG dysfunction in recipient mice, only if the recipients were primed with alum. In vitro, antibodies from Ro52-immune sera were internalized by a SG cell line and this uptake was inhibited by Cytochalasin D treatment. Conclusion Our data shows for the first time that antibodies induced by Ro52 are capable of inducing SG dysfunction, and that this phenomenon is dependent on the activation of innate immunity. The mouse model described in this study implies that autoantibody deposition in the SG might be an important step in the induction of xerostomia and pathogenesis of SS.

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“…This suggests Ro52+ (not only the antibody) may have an important role in autoimmunity 34 35. The expression of Ro52 protein correlates with inflammation in autoimmune diseases, for example, salivary glands in primary SS 36. Although these antibodies have been reported in many autoimmune diseases,37 they are not specific given that they have been detected in other systemic conditions without autoimmune features 27 38 39.…”

Section: Introductionmentioning

confidence: 99%

Clinical associations of the positive anti Ro52 without Ro60 autoantibodies: undifferentiated connective tissue diseases

Murng

Thomas

2017

J Clin Pathol

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AimsAutoantibodies targeting Ro52 and Ro60 antigens are historically reported as anti SSA/Ro. In general anti SSA/Ro results are either anti Ro52+Ro60+ or anti Ro52−Ro60+ antibodies. Anti Ro52 without anti Ro60 (Ro52+ Ro60−) antibodies are often not reported routinely. This study intends to review the potential significance of these autoantibodies in the management of connective tissue diseases.MethodA retrospective survey of Ro52+Ro60− was carried out as part of the service evaluation of extractable nuclear antigen antibodies (ENA) reporting from the immunology laboratory, the NHS Greater Glasgow and Clyde (GGC), UK. The clinical documents and laboratory results of 97 patients with Ro52+Ro60− and 100 patients with Ro52+Ro60+ were reviewed.ResultsSeventy-one patients (73%) with anti Ro52+Ro60− antibodies have been diagnosed with autoimmune conditions including undifferentiated connective tissue diseases (n=14, 14%), systemic lupus erythematosus (n=10, 10%), Sjögren’s syndrome (n=10, 10%) and rheumatoid arthritis (n=13, 13%). Twenty-three patients (24%) with anti Ro52+Ro60− antibodies have no autoimmune features but were found to have significant clinical conditions including malignancies. In contrast, 87 patients (87%) with anti Ro52+Ro60+ antibodies have autoimmune conditions including Sjögren’s syndrome (n=34, 34%), systemic lupus erythematosus (SLE; n=23, 23%), undifferentiated connective tissue diseases (n=12, 12%) and rheumatoid arthritis (n=6, 6%).ConclusionAnti Ro52 without anti Ro60 (Ro52+Ro60−) antibodies should be reported. In the majority of patients these autoantibodies were associated with various autoimmune diseases. Anti Ro52+Ro60− antibodies were also found in patients with significant clinical conditions including malignancies even though there was no suggestion of autoimmunity at the time of testing.

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Ductal epithelial expression of Ro52 correlates with inflammation in salivary glands of patients with primary Sjögren's syndrome

Cited by 28 publications

References 41 publications

Update on Pathogenesis of Sjogren's Syndrome

Update on Pathogenesis of Sjogren's Syndrome

Interaction between innate immunity and Ro52-induced antibody causes Sjögren's syndrome-like disorder in mice

Clinical associations of the positive anti Ro52 without Ro60 autoantibodies: undifferentiated connective tissue diseases

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