Sex Differences in Systemic Lupus Erythematosus

Nusbaum, Julie; Mirza, Ibraheem; Shum, Justine; Freilich, Robert W.; Cohen, Rebecca E.; Pillinger, Michael H.; Izmirly, Peter; Buyon, Jill P.

doi:10.1016/j.mayocp.2019.09.012

Cited by 108 publications

(55 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, the MRL/lpr mouse strain is a model for more rapid and aggressive onset of SLE due to Fas (CD95) mutation, with the generation of autoantibodies as early as 6 weeks and advanced renal disease (glomerulonephritis) around 16 weeks (40). Female mice were used in this study due to greater propensity to develop ADs in women (41)(42)(43).…”

Section: Differential Autoimmune Responses In Lupus-resistant/-prone Micementioning

confidence: 99%

Aberrant Gut Microbiome Contributes to Intestinal Oxidative Stress, Barrier Dysfunction, Inflammation and Systemic Autoimmune Responses in MRL/lpr Mice

Wang

Banerjee

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Microbiome composition and function have been implicated as contributing factors in the pathogenesis of autoimmune diseases (ADs), including systemic lupus erythematosus (SLE), rheumatoid arthritis and autoimmune hepatitis (AIH). Furthermore, dysbiosis of gut microbiome is associated with impaired barrier function and mucosal immune dysregulation. However, mechanisms by which gut microbiome contributes to the ADs and whether antioxidant treatment can restore gut homeostasis and ameliorate the disease outcome are not known. This study was, therefore, focused on examining the involvement of gut microbiome and host responses in the pathogenesis of SLE using unique female mouse models (C57BL/6, MRL+/+ and MRL/lpr) of 6 and 18 weeks with varying degrees of disease progression. Fecal microbiome diversity and composition, gut oxidative stress (OS), barrier function and inflammation, as well as systemic autoimmunity were determined. Interestingly, each mouse strain had distinct bacterial community as revealed by β-diversity. A lower Firmicutes/Bacteroidetes ratio in 6-week-old MRL/lpr mice was observed, evidenced by decrease in Peptostreptococcaceae under Firmicutes phylum along with enrichment of Rikenellaceae under Bacteroidetes phylum. Additionally, we observed increases in colonic OS [4-hydroxynonenal (HNE)-adducts and HNE-specific immune complexes], permeability changes (lower tight junction protein ZO-2; increased fecal albumin and IgA levels) and inflammatory responses (increased phos-NF-κB, IL-6 and IgG levels) in 18-week-old MRL/lpr mice. These changes were associated with markedly elevated AD markers (antinuclear and anti-smooth muscle antibodies) along with hepatic portal inflammation and severe glomerulonephritis. Notably, antioxidant N-acetylcysteine treatment influenced the microbial composition (decreased Rikenellaceae; increased Akkeransiaceae, Erysipelotrichaceae and Muribaculaceae) and attenuated the systemic autoimmunity in MRL/lpr mice. Our data thus show that gut microbiome dysbiosis is associated with increased colonic OS, barrier dysfunction, inflammatory responses and systemic autoimmunity markers. These findings apart from delineating a role for gut microbiome dysbiosis, also support the contribution of gut OS, permeability changes and inflammatory responses in the pathogenesis of ADs.

show abstract

Section: Differential Autoimmune Responses In Lupus-resistant/-prone Micementioning

confidence: 99%

Aberrant Gut Microbiome Contributes to Intestinal Oxidative Stress, Barrier Dysfunction, Inflammation and Systemic Autoimmune Responses in MRL/lpr Mice

Wang

Banerjee

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…The probability of developing autoimmunity phenomena is based on genetic predisposition, which involves human leukocyte antigens (HLA) polymorphisms [51] and some non-HLA genes [52] ; the effect of gender, being more common in the female gender [53] ; age, being more common in reproductive age due to the effect of estrogens [54] ; a family history of autoimmune diseases [55] ; an individual history of autoimmune diseases (which makes an individual more susceptible to developing another autoimmune condition) [56] ; and the presence of autoantibodies such as anti-nuclear antibodies [57] . Each of these predisposing components are additive when evaluating individual susceptibility for developing autoimmunity [58] , which is a condition where a tendency to lose immune self-tolerance is observed [59] .…”

Section: Testing the Hypothesismentioning

confidence: 99%

The triggering of post-COVID-19 autoimmunity phenomena could be associated with both transient immunosuppression and an inappropriate form of immune reconstitution in susceptible individuals

Cañas

2020

Medical Hypotheses

View full text Add to dashboard Cite

With the progression of the COVID-19 pandemic, there have been different reports about the development of autoimmune diseases once the infection is controlled. After entering the respiratory epithelial cells, SARS-CoV-2—the virus that causes the disease—triggers a severe inflammatory state in some patients known as “cytokine storm” and the development of thrombotic phenomena—both conditions being associated with high mortality. Patients additionally present severe lymphopenia and, in some cases, complement consumption and autoantibody development. There is a normalization of lymphocytes once the infection is controlled. After this, autoimmune conditions of unknown etiology may occur. A hypothesis for the development of post-COVID-19 autoimmunity is proposed based on the consequences of both a transient immunosuppression (both of innate and acquired immunity) in which self-tolerance is lost and an inappropriate form of immune reconstitution that amplifies the process.

show abstract

“…NK Cells and SLE SLE is a progressive autoimmune disease with variable clinical manifestations affecting several organs including skin, lungs, blood, heart, and nervous system (43). It is characterized by the presence of nuclear autoantibodies along with abnormally activated T cells and hyperactive B cells, which form immune complexes that lead to inflammation (4,(44)(45)(46).…”

Section: Nk Cells and Autoimmune Diseases Nk Cells And Systemic Autoimentioning

confidence: 99%

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

2021

View full text Add to dashboard Cite

Autoimmune diseases generally result from the loss of self-tolerance (i.e., failure of the immune system to distinguish self from non-self), and are characterized by autoantibody production and hyperactivation of T cells, which leads to damage of specific or multiple organs. Thus, autoimmune diseases can be classified as organ-specific or systemic. Genetic and environmental factors contribute to the development of autoimmunity. Recent studies have demonstrated the contribution of innate immunity to the onset of autoimmune diseases. Natural killer (NK) cells, which are key components of the innate immune system, have been implicated in the development of multiple autoimmune diseases such as systemic lupus erythematosus, type I diabetes mellitus, and autoimmune liver disease. However, NK cells have both protective and pathogenic roles in autoimmunity depending on the NK cell subset, microenvironment, and disease type or stage. In this work, we review the current knowledge of the varied roles of NK cell subsets in systemic and organic-specific autoimmune diseases and their clinical potential as therapeutic targets.

show abstract

Sex Differences in Systemic Lupus Erythematosus

Cited by 108 publications

References 93 publications

Aberrant Gut Microbiome Contributes to Intestinal Oxidative Stress, Barrier Dysfunction, Inflammation and Systemic Autoimmune Responses in MRL/lpr Mice

Aberrant Gut Microbiome Contributes to Intestinal Oxidative Stress, Barrier Dysfunction, Inflammation and Systemic Autoimmune Responses in MRL/lpr Mice

The triggering of post-COVID-19 autoimmunity phenomena could be associated with both transient immunosuppression and an inappropriate form of immune reconstitution in susceptible individuals

NK Cells in Autoimmune Diseases: Protective or Pathogenic?

Contact Info

Product

Resources

About