Anti-Ro and anti-La autoantibody profiling in Norwegian patients with primary Sjögren’s syndrome using luciferase immunoprecipitation systems (LIPS)

Volchenkov, Roman; Jönsson, Roland; Appel, Silke

doi:10.3109/03009742.2012.670863

Cited by 13 publications

(10 citation statements)

References 9 publications

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“…Another prominent feature of SS is the high production of autoantibodies against the intracellular proteins Ro/SSA and La/SSB, which can be detected in both the peripheral blood [20][21][22] and SG [23][24][25] of SS patients. Recently, it was reported that most primary SS patients produce autoantibodies many years before symptom onset [26,27].…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue is prominent in salivary glands of Sjögren’s syndrome patients and appears to influence the microenvironment in these organs

et al. 2016

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A minor salivary gland (SG) biopsy with focal lymphocytic sialadenitis and a focus score of ≥1 is today's widely accepted pathological finding confirming the SG component of Sjögren's syndrome (SS). Adipocytes can occupy a large percentage of the SG area although little is known about their significance in SS lesions. This study aimed to characterise adipose tissue infiltration in labial SG biopsies from 27 SS patients and 28 non-SS sicca controls. Biopsies were evaluated by one oral pathologist and assessed for focus score, acinar atrophy, fatty replacement and non-specific chronic inflammation. Moreover, to explore the SG microenvironment, immunohistochemical staining of paraffin-embedded SG tissue was performed using interleukin-6 (IL-6). The fatty replacement was evident in all SS patients possessing autoantibodies (Ro/SSA and/or La/SSB) as well as a positive SG biopsy (focus score ≥1). Additionally, 62% of SS patients having autoantibodies but a negative biopsy showed fatty infiltration (FI) while non-SS controls demonstrated fatty replacement in only 32% of the cases. Overall, the SS group (mean age 53.0 years) had a significantly higher incidence (p value 0.005) of FI than the non-SS controls (mean age 54.8 years). Interestingly, adipocytes were located in IL-6 rich areas, and IL-6 positive adipocytes were detected. As fat deposition seems to be more recurrent in SGs affected by SS, we propose the assessment of adipose tissue replacement as a helpful tool for diagnostic evaluation in SS. Detection of IL-6 positive adipocytes suggests their involvement in immune reactions. Still, functional studies are needed to investigate the SG microenvironment further.

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Section: Introductionmentioning

confidence: 99%

Adipose tissue is prominent in salivary glands of Sjögren’s syndrome patients and appears to influence the microenvironment in these organs

et al. 2016

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“…In addition to high serum titres of autoantibodies , a fundamental diagnostic feature of SS is chronic inflammation manifested by mononuclear cell infiltration of exocrine glands, particularly lachrymal and salivary glands (SG) . A process starts that eventually results in the replacement of the glandular epithelium by infiltrating mononuclear cells, leading to dysfunction and later destruction of the glands .…”

Section: Introductionmentioning

confidence: 99%

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

Aqrawi

Kvarnström

Brokstad

et al. 2014

Clinical and Experimental Immunology

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SummaryRo52 is an E3 ubiquitin ligase with a prominent regulatory role in inflammation. The protein is a common target of circulating autoantibodies in rheumatic autoimmune diseases, particularly Sjögren's syndrome (SS). In this study we aimed to investigate the expression of the SS target autoantigen Ro52 in salivary glands of patients with primary Sjögren's syndrome (pSS). Ro52 expression was assessed by immunohistochemical staining of paraffinembedded and frozen salivary gland biopsies from 28 pSS patients and 19 non-pSS controls from Swedish and Norwegian registries, using anti-human Ro52 monoclonal antibodies. The degree and pattern of staining and inflammation was then evaluated. Furthermore, secreted Ro52 protein was measured in saliva and serum samples from the same individuals through a catch-enzyme-linked immunosorbent assay (ELISA). Ro52 was highly expressed in all the focal infiltrates in pSS patients. Interestingly, a significantly higher degree of Ro52 expression in ductal epithelium was observed in the patients compared to the non-pSS controls (P < 0·03). Moreover, the degree of ductal epithelial expression of Ro52 correlated with the level of inflammation (Spearman's r = 0·48, P < 0·0120). However, no secreted Ro52 protein could be detected in serum and saliva samples of these subjects. Ro52 expression in ductal epithelium coincides with degree of inflammation and is up-regulated in pSS patients. High expression of Ro52 might result in the breakage of tolerance and generation of Ro52 autoantibodies in genetically susceptible individuals. We conclude that the up-regulation of Ro52 in ductal epithelium might be a triggering factor for disease progression in SS.

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“…Luciferase immunoprecipitations systems (LIPS) utilizes light-emitting recombinant antigens to detect autoantibodies with high sensitivity and specificity in different autoimmune conditions [31] including SLE [28] and SS [32][33][34][35][36]. This is because LIPS is a fluidphase immunoassay that presents autoantigens such as cytokines in solution, allowing them to adopt native structures.…”

Section: Introductionmentioning

confidence: 99%

Clinical features of Sjögren's syndrome patients with autoantibodies against interferons

Burbelo

Browne

Holland

et al. 2019

Clinical & Translational Med

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Background Sjögren’s syndrome (SS) is an autoimmune disease characterized by immune attack on the salivary and lacrimal glands. Given the known cytokine activation and type I interferon gene expression signature found in SS, we hypothesized that anticytokine autoantibodies might be detectable by Luciferase immunoprecipitation systems in some SS patients and correlate with clinical symptoms. Results Luciferase immunoprecipitation systems was used to screen for serum anti-cytokine autoantibodies in 57 primary SS patients and 25 healthy volunteers. Autoantibodies were detected against GMCSF, interferon-γ, -α and, -ω in one, two, two and six patients with SS, respectively. None of the healthy volunteers showed anticytokine autoantibodies and none of the SS or control subjects showed autoantibodies against interferon-λ. One 51-year old female SS subject with the highest anti-interferon-α and -ω autoantibody levels had stable autoantibody levels over the course of a year. In vitro functional testing of serum autoantibodies from this subject demonstrated partially neutralizing activity for interferon-α signaling. Clinical information on this individual revealed a low focus score and high levels of unstimulated salivary flow, suggesting the possibility that interferon-α autoantibody neutralizing activity may have contributed to the milder sicca symptoms. Conclusion Overall, these findings demonstrate that a subset of SS patients (16%) harbor autoantibodies against GMCSF, interferon-γ, interferon-ω, and interferon-α. These data support the observation that high levels of interferon-α autoantibodies may attenuate disease symptoms in SS.

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Anti-Ro and anti-La autoantibody profiling in Norwegian patients with primary Sjögren’s syndrome using luciferase immunoprecipitation systems (LIPS)

Cited by 13 publications

References 9 publications

Adipose tissue is prominent in salivary glands of Sjögren’s syndrome patients and appears to influence the microenvironment in these organs

Adipose tissue is prominent in salivary glands of Sjögren’s syndrome patients and appears to influence the microenvironment in these organs

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

Clinical features of Sjögren's syndrome patients with autoantibodies against interferons

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