The role of the intestinal microbiome in antiphospholipid syndrome

Abstract

The antiphospholipid syndrome (APS) is a thrombotic autoimmune disease in which the origin of the disease-characterizing autoantibodies is unknown. Increased research effort into the role of the intestinal microbiome in autoimmunity has produced new insights in this field. This scoping review focusses on the gut microbiome in its relation to APS. EMBASE and MEDLINE were searched for original studies with relevance to the relation between the gut microbiome and APS. Thirty studies were included. Work on systemic lupus erythematosus, which strongly overlaps with APS, has shown that patients often display an altered gut microbiome composition, that the disease is transferable with the microbiome, and that microbiome manipulation affects disease activity in murine lupus models. The latter has also been shown for APS, although data on microbiome composition is less consistent. APS patients do display an altered intestinal IgA response. Evidence has accrued for molecular mimicry as an explanatory mechanism for these observations in APS and other autoimmune diseases. Specific gut microbes express proteins with homology to immunodominant APS autoantigens. The disease phenotype appears to be dependent on these mimicking proteins in an APS mouse model, and human APS B- and T-cells indeed cross-react with these mimics. Pre-clinical evidence furthermore suggests that diet may influence autoimmunity through the microbiome, as may microbial short chain fatty acid production, though this has not been studied in APS. Lastly, the microbiome has been shown to affect key drivers of thrombosis, and may thus affect APS severity through non-immunological mechanisms. Overall, these observations demonstrate the impact of the intestinal microbiome on autoimmunity and the importance of understanding its role in APS.

An Intestinal Microbiome Intervention Affects Biochemical Disease Activity in Patients with Antiphospholipid Syndrome

“…The findings in APS patients complement in vitro data, mouse studies, and human observational studies on the role of the gut microbiota in APS. 3,5,7 Measuring disease activity poses a challenge in smaller human APS studies, given the infrequency of clinical events and the range of cell types and extracellular proteases involved in the pathogenesis. This novel approach represents an integral and unbiased method to assess the APS biochemical phenotype.…”

“…2 The intestinal microbiome, the community of microorganisms that colonizes the intestinal tract, poses a chronic exposure to a broad variety of microbial antigens and is thus hypothesized to drive the formation of persistent APLAs. 3 The gut microbiota indeed can trigger autoimmunity through antigen cross-reactivity. For several autoimmune disorders, including APS, gut bacteria that contain peptide sequence homologues to the epitopes of autoantigens have been identified, resulting in antigen cross-reactivity.…”

Antiphospholipid Antibodies Associated with Native Arteriovenous Fistula Complications in Hemodialysis Patients: A Comprehensive Review of the Literature

“…aPL positivity might also be explained by molecular mimicry as a response to the exposure to microorganisms, such as hepatitis C virus [ 26 , 27 ], exposure to endotoxins related either to ESKD, or to HD. Also, the role of the gut microbiota modification in ESKD has been suggested [ 28 , 29 ]. Hemodialysis membranes have also been associated with higher incidence of aPL (e.g., cuprophane membranes) [ 30 ].…”

Systemic lupus erythematosus and antiphospholipid syndrome: past, present, future

“…), вызывающих активацию эндотелиальных клеток, тромбоцитов, нейтрофилов [35][36][37][38]. Обсуждается значение дополнительных иммунологических механизмов, частично перекрещивающихся с СКВ, включая нарушения эпигенетической регуляции [39], кишечной микробиоты [40], активацию Th17-клеток [41], В-клеток [42], плазмабластов, гиперпродукцию ИФН типа I и других цитокинов [43][44][45], дефекты фолликулярных Т рег клеток [46]. Поскольку у здоровых людей обнаружение аФЛ не ассоциируется с развитием тромбозов, а при АФС они развиваются эпизодически, предполагается участие дополнительных стимулов, индуцирующих острое развитие тромбоза.…”