Integrating intestinal microbiota into systemic lupus erythematosus (SLE) pathogenesis. Integrating intestinal microbiota into systemic lupus erythematosus.

Slides:

Advertisements

Similar presentations

The Complement System Andrew E Thompson MD FRCPC Fellow in Rheumatology University of British Columbia.

Advertisements

Hypothesis 1: Chimerism induces a graft-versus-host reaction Host B lymphocyte B B B B Chimeric Th lymphocyte Chimeric CTL Stimulation No elimination or.

Innate and Adaptive Immunity

AUTOIMMUNITY. Self/Non-self Discrimination Autoimmunity is a problem of self/non-self discrimination.

AUTOIMMUNITY. Autoimmunity Breaking of self tolerance Both B and T cells may be involved (however, most are antibody mediated)

CATEGORY: IMMUNE DYSFUNCTION Systemic Lupus Erythematosus (SLE) Angela Midgley, University of Liverpool, UK S YSTEMIC L UPUS E RYTHEMATOSUS © The copyright.

GENERAL IMMUNOLOGY PHT 324

Chapter 43 The Immune System.

Daily Warm-up March 19th During the Quarter Quell, Katniss Everdeen searches for water in the arena. Before she found it, she began to become dehydrated.

Autoimmune Disorders During Pregnancy -Lupus -Antiphospholipid syndrome Rovnat Babazade, MD Obstetrical Anesthesia-2016.

Mannose Binding Lectin (MBL) Pathway

The Complement System Andrew E Thompson MD FRCPC

Systemic lupus erythematosus

Objective 17 Hypersensitivity

Systemic Lupus Erythematosus (SLE)

Inflamm Intest Dis 2016;1: DOI: /

Autoimmune diseases Ch. 4 p (99 – 159) March 7 /2016 March

“Systemic Lupus Erythematosus” (SLE): Pathophysiology

Mechanisms of Autoimmunity Department of Pathology

Autoimmune Diseases Autoimmune Diseases Presented By Dr. Manal Yassin.

“Systemic Lupus Erythematosus” (SLE)

Mechanisms of Autoimmunity

Immunological Tolerance and Autoimmune Diseases

Systemic Lupus Erythematosus

AUTOIMMUNE DISEASES.

Figure 2 Cell-mediated disease mechanisms of lupus nephritis

Nat. Rev. Nephrol. doi: /nrneph

Figure 3 Proposed mechanisms underlying the links

Immunogens and Antigens

Food Allergies: The Basics

Agustín Albillos, Margaret Lario, Melchor Álvarez-Mon

Microbial Influences in Inflammatory Bowel Diseases

Figure 4 Antinuclear antibodies and disease activity in SLE

Gluten and IgA nephropathy: you are what you eat?

Figure 3 Nucleic acid sensors in SLE

Nat. Rev. Nephrol. doi: /nrneph

Pathogenesis of primary biliary cirrhosis

Nat. Rev. Rheumatol. doi: /nrrheum

(A) Lequesne index and quadriceps strength of patients with knee OA

Management of hyperuricaemia in patients with gout according to the European League Against Rheumatism recommendations. Management of hyperuricaemia in.

Figure 1 The current model of the pathogenesis of SLE

References Kuby Immunology 7th Edition 2013 Chapter 16 Pages Pages

Role of IgE in autoimmunity

Figure 1 Sequence of events in the development of autoimmune nephritis

William G. Couser, Richard J. Johnson Kidney International

Autoimmunity Immunology.

Figure 2 Cellular contributions to the development of SLE

Pathogenesis of primary biliary cirrhosis

Mechanisms of Autoimmunity Department of Pathology

Hans-Joachim Anders, Detlef O. Schlondorff Kidney International

Autoimmunity Semester : III Course Title : Immunology Unit : III

SLE: the many players involved in systemic autoimmunity and tissue destruction. SLE: the many players involved in systemic autoimmunity and tissue destruction.

Nat. Rev. Rheumatol. doi: /nrrheum

Achilles tendon tear. Achilles tendon tear. (A) Longitudinal and (B) transverse images of the calf: at the middle third of the left Achilles tendon there.

Heterogeneity of TCRβ repertoire in autoimmune diseases.

Increased numbers of LDGs in association with disease activity and low complement levels in patients with SLE. Numbers of LDGs were determined by flow.

Frequency distribution of the number of fulfilled classification criteria for RA (ACR 1987) in relation to the proportion of positive anti-CCP antibodies.

(A–F) Changes of B-cell numbers and B-cell related biomarkers.

Mean disease activity score based on a 28-joint count (DAS28 (ESR)) (A), Clinical Disease Activity Index (CDAI) score (B) and Simplified Disease Activity.

Serial determinations of both anti-chromatin and anti-dsDNA antibodies in a patient who developed lupus nephropathy during the study period, showing that.

Status of tapering in the first year of follow-up.

Ultrasonographic picture of second metatarsophalangeal joint with synovitis (panel A) and without synovitis (panel B). a, metatarsal head; b, base of.

Seven weeks after presentation: scattered posterior pole intra-retinal haemorrhages and cotton wool spots; right eye (A) and left eye (B). Seven weeks.

Statistically significant correlation between the expression of FRP2 or BLT1 in monocytes and different parameters such as ESR (p: 0,0166; r: -0,434),

Changes over time of the daily prednisone dose in patients that responded to anakinra. Changes over time of the daily prednisone dose in patients that.

Patient disposition. *n=1 patient took prohibited concomitant medication due to an adverse event and was discontinued from the study. Patient disposition.

Average annual price for csDMARDs (A) and bDMARDs (B) per country in international dollars (light blue) and in euros (dark blue), prices first quarter.

The right hand of the same patient as in figure 1, photographed from the ulnar side, showing dorsolateral nodes in profile on the index and ring fingers,

(A) A barium follow-through showing a dilated oesophagus with markedly dilated loops of the small bowel; (B) abdominal computed tomography showing dilated,

Baker’s cyst (photomontage).

Presentation transcript:

Integrating intestinal microbiota into systemic lupus erythematosus (SLE) pathogenesis. Integrating intestinal microbiota into systemic lupus erythematosus (SLE) pathogenesis. (A) Exposure to various sterile and/or infectious stimuli can lead to apoptosis or NETosis contributing to release of modified self-antigen (DNA). Genetic susceptibility and/or defective clearance results in presentation of these modified self-antigens to T cells followed by B cell activation and eventually production of anti-DNA antibodies, well-known for their association with lupus nephritis. (B) Dysbiosis in patients with SLE with fivefold overabundance of Ruminococcusgnavus (RG) leads to barrier disruption and loss of systemic tolerance with subsequent development of anti-RG antibodies mainly directed towards the fragment RG2 (anti-RG2 antibodies). RG2-containing pools included moieties that were potent in vitro activators via toll-like receptor 2 (TLR2) (previously been implicated in lupus pathogenesis), illustrated by Azzouz et al 5 by elevated serum interferon alpha 2. (C) SLE may be triggered or augmented through intestinal dysbiosis and a molecular mimicry process between a lipoglycan expressed on the cell wall of RG and native DNA molecules (1) Loss of systemic tolerance due to over abundance of RG and/or the formation of immune complexes may lead to augmented stimulation of innate immunity and subsequent enhanced presentation of self antigen followed by production of anti DNA antibodies. (2) Type1 interferon has a critical role in SLE pathogenesis. (3) Anti-DNA antibodies cross-react with RG2, more specifically the lipoglycan 3 cell wall expressing the immunodominant epitopes. Cross-reactivity of lupus autoreactive B cells to leaked stimulatory RG bacterial components, including TLR ligands(s), may contribute to the initiation and/or flares of SLE. (4) Kidney injury by direct antibody binding or by deposition of immune complexes. Isabelle Peene, and Dirk Elewaut Ann Rheum Dis 2019;78:867-869 ©2019 by BMJ Publishing Group Ltd and European League Against Rheumatism