Preclinical Systemic Lupus Erythematosus

Robertson, Julie M.; James, Judith A.

doi:10.1016/j.rdc.2014.07.004

Cited by 38 publications

(32 citation statements)

References 49 publications

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“…Altered immune mediators are linked to SLE pathogenesis (15) and may be altered prior to disease classification (26). Utilizing a nested, case-control, approach, we assessed plasma levels of 52 soluble mediators from multiple immune pathways (Supplementary Table 1) in the 45 relatives who transitioned to classified SLE vs. non-transitioned relatives matched by race, gender, and age ± 5 years (n=90, 45 ANA positive and 45 ANA negative non-transitioned relatives, Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Altered plasma soluble mediator levels in relatives who transitioned to classified SLE. Altered levels of immune mediators are linked to SLE pathogenesis (15) and appear before disease classification (26). Utilizing a nested case-control approach, we assessed the plasma levels of 52 soluble mediators from multiple immune pathways (15) in the 45 relatives who transitioned to classified SLE compared to 90 nontransitioned relatives who were matched by race, sex, and age (65 years) (comprising 45 ANA-positive nontransitioned relatives and 45 ANAnegative nontransitioned relatives) ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

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Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features

Munroe

Young

Kamen

et al. 2017

Arthritis & Rheumatology

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Objective Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential to curtail irreversible inflammatory damage. The objective of this study was to identify factors associated with transition to classified disease that inform SLE risk. Methods Previously identified lupus patient blood relatives with < 4 American College of Rheumatology SLE classification criteria at baseline (n=409) were enrolled in this follow-up study. Participants provided detailed family, demographic, and clinical information, including the SLE-specific portion of the Connective Tissue Disease Screening Questionnaire (SLE-CSQ). Plasma samples were tested for the presence of lupus-associated autoantibodies and 52 soluble mediators. Generalized estimating equations (GEE) were applied to identify factors anticipating disease transition. Results Forty-five relatives (11%) transitioned to classified SLE during follow-up (mean time=6.4 years). Relatives who transitioned displayed more lupus-associated autoantibody specificities and higher SLE-CSQ scores (p<0.0001) at baseline than non-transitioned relatives. Importantly, they also had elevated baseline plasma levels of inflammatory mediators, including B-lymphocyte stimulator (BLyS), stem cell factor (SCF), and interferon-associated chemokines (p≤0.02), with concurrent decreases in levels of regulatory mediators, tumor growth factor (TGF)-β and interleukin (IL)-10 (p≤0.03). GEE revealed that baseline SLE-CSQ or ACR scores and plasma levels of SCF and TGF-β (p≤0.03), but not autoantibodies, were significant and independent predictors of SLE transition. Conclusions Altered levels of soluble mediators anticipate transition to classified disease in lupus relatives. Thus, immune perturbations precede SLE classification and can help identify high-risk relatives for rheumatology referral and potential enrollment in prevention trials.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features

Munroe

Young

Kamen

et al. 2017

Arthritis & Rheumatology

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“…The appropriate diet would be expected to enrich beneficial commensals or metabolites that naturally control pathobiont overgrowth. In the future, asymptomatic but autoimmune-prone individuals with heightened pDC and type I IFN pathways might benefit from personalized diets tailored to their microbiota composition (Bourn and James, 2016; Kau et al, 2011; Robertson and James, 2014). Because the type I IFN pathway is involved in various chronic inflammatory and metabolic diseases, identifying strains in the microbiota that fuel this pathway might have implications beyond autoimmunity (Ganguly, 2018).…”

Section: Discussionmentioning

confidence: 99%

A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity

Zegarra-Ruiz

Beidaq

Iñiguez

et al. 2019

Cell Host & Microbe

235

237

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Summary Western lifestyle is linked to autoimmune and metabolic diseases, driven by changes in diet and gut microbiota composition. Using a Toll-like receptor 7 (TLR7)-dependent mouse models of lupus, we dissect dietary effects on the gut microbiota and find that Lactobacillus reuteri can drive autoimmunity but is ameliorated via dietary resistant starch (RS). Culture of internal organs and 16S rDNA sequencing revealed TLR7-dependent translocation of Lactobacillus reuteri in mice and fecal enrichment of Lactobacillus in a subset of lupus patients. L. reuteri colonization worsened autoimmune manifestations under specific-pathogen-free and gnotobiotic conditions, notably increasing plasmacytoid dendritic cells (pDCs) and interferon signaling. However, RS suppressed the abundance and translocation of L. reuteri via short-chain fatty acids, which inhibited its growth. Additionally, RS decreased pDCs, interferon pathways, organ involvement and mortality. Thus, RS exerts beneficial effects in lupus-prone hosts through suppressing a pathobiont that mediates interferon pathways implicated in the pathogenesis of human autoimmunity.

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“…However, this autoantibody may be found in some situations where its meaning is not completely clear and this may represent a diagnostic challenge, mainly when the test is persistently positive [1]. Autoimmune diseases such as systemic lupus (SLE) or rheumatoid arthritis (RA) may have positivity for autoantibodies several years before its appearance [2]. A positive ANA in this context may represent a state of pre-autoimmunity [2].…”

Section: Introductionmentioning

confidence: 99%

Anti-nuclear antibodies in patients with breast cancer

Nisihara

Machoski

Neppel

et al. 2018

Clinical and Experimental Immunology

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To study the prevalence of anti-nuclear antibodies (ANA) in breast cancer patients and its association with tumour characteristics. Ninety-one patients with breast mass detected by image studies and assigned to conduct diagnostic biopsy and eventual surgical treatment were studied for demographical, tumour data and presence of ANA. Serum of positive ANA patients was screened for the extractable nuclear antigen (ENA) profile. As comparison, 91 healthy individuals matched for age and from the same geographical area were included. In this sample 72 of 91 (79·1%) had malignant lesions (83% ductal infiltrative carcinoma). ANA was positive in 44·4% of patients with malignant tumour and in 15·7% of those with benign lesions (malignant versus benign with P = 0·03). Controls had ANA positivity in 5·4%, and when compared with tumour samples showed P < 0·0001. The most common immunofluorescence pattern was a fine dense speckled pattern. In the ANA-positive patients with malignant lesions, seven had positivity for ENA profile (three for anti-RNP and anti-Sm, one for just anti-RNP, two for anti-Ro and anti-La e two for just anti-La). It was not possible to associate ANA positivity with tumour histological characteristics or staging or with patient's age. A negative association of ANA with hormonal (oestrogen or oestrogen plus progesterone) receptor status was found (P = 0·01). In this sample, there was a high prevalence of ANA positivity in breast cancer patients with a negative association with the presence of hormonal receptors. More studies are needed to understand the real value of this finding.

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Preclinical Systemic Lupus Erythematosus

Cited by 38 publications

References 49 publications

Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features

Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features

A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity

Anti-nuclear antibodies in patients with breast cancer

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