Newton001 Pregnancy in Lupus: gestational, immunological and vascular risk factors and outcomes

Lead Research Organisation: University of Manchester
Department Name: Medical and Human Sciences

Abstract

Two of the most serious health problems facing Brazil today are childhood and motherhood mortality, which outstrip the UK by 6- and 10 -fold, respectively. The reasons for this divide are multifactorial, but shared knowledge between the UK and Brazil could feasibly impact upon these figures.
Systemic Lupus Erythematosus (SLE), often termed Lupus, is an autoimmune disorder that frequently affects women in their child-bearing years. When superimposed on pregnancy, Lupus and Lupus-like disorders (LLD) significantly increase the incidence of all major obstetric complications, including miscarriage, stillbirth, high blood pressure, premature birth and fetal growth restriction. These women are therefore a major obstetric concern, regardless of their country of origin or clinical setting.
Clinically, the optimal care, treatment and monitoring of this group are still evolving. This application seeks to harmonise and expand the research/expertise in the study and management of these pregnancies, through the active exchange of ideas, research and best practice between the UK and Brazil.
This project brings together two renowned facilities for the study of these complex pregnancies, one in Rio de Janeiro the other Manchester, both with a wealth of obstetric and rheumatology experience. In coordinating our research efforts, our joint aims are to better define the key vascular, endocrine and immunological factors which drive poor pregnancy outcome in these affected women. By standardising clinical and research protocols across centres, sharing data and study samples, current research projects will be enhanced and joint initiatives developed. Moreover, by maximising clinical practice across centres, the stratification of SLE/LLD patients according to their pregnancy risk will be improved, with potential immediate benefits in patient care and clinical guidelines.

Technical Summary

The joint aims in this UK/Brazil collaboration are to better define the key vascular, endocrine and immunological factors which drive poor pregnancy outcome in women with SLE/LLD. This will be achieved by standardizing both clinical practice and research protocols across centres, sharing data and study samples, research and clinical expertise.
Firstly, through direct face-to-face discussions, consensus on standardization of protocols and approaches will be developed. This standardization will include clinical and demographic data, sample collections (blood and placenta), and Doppler and vascular assessments of pregnancy. In addition, laboratory-based assays will be performed at each site. Plasma investigations of T cell subsets (Treg/Th17 cells) and their induction will be conducted, and inflammatory cytokines (IL-6,IL-10, TGFb), angiogenic and anti-angiogenic factors (VEGF, PlGF, SFlt-1) and complement and autoantibodies quantified. Collected placental tissues will undergo full pathologic interpretation and processed for complement deposition; as markers of SLE/LLD severity and in vivo placental impact. Bio-banked samples and data at both centres will be shared for this and future collaborative ventures.
These studies will generate 2 key outputs. Firstly, they will improve stratification of SLE/LLD subsets according to pregnancy risk. Secondly, data will inform future interventional studies. The standardization of current practice across centres will have immediate impact on care. In addition, the exchange of clinical experience, improving definitions and treatment options by agreement and consensus will help guarantee longevity of the collaboration beyond the life of the project.

Planned Impact

N/A
 
Description Our work has established methods to assess immune function in women with rheumatic diseases who are pregnant.
This allows more detailed measurement of their immune system and how this may affect the outcomes of their pregnancy.
This methodology was shared with our colleagues in Rio De Janeiro who also hope to take this in to future studies.
Our Brazilian partners have also developed work on biomarkers to assess placental function in pregnancy and future work will include our site in Manchester
Exploitation Route This work has set our group up to now participate in future rheumatology/pregnancy studies and we hope future funding will follow
Sectors Healthcare

 
Description We have an ongoing relationship with our partners in Rio. A number of their team attended a conference in Manchester in Sept 2019 and we discussed future collaboration and student exchanges This clinical and academic exchanges will continue to develop UK-Brazilian relationships with future exchange visits planned in 2020-21
First Year Of Impact 2019
Sector Healthcare
Impact Types Cultural

 
Description British Society for Rheumatology SLE Guidelines
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Newton Award Collaboration with Rio de Janeiro 
Organisation Federal University of Rio de Janeiro
Country Brazil 
Sector Academic/University 
PI Contribution Our collaborators in Rio have not received their funding as yet but they are trained up to start collecting data in Brazil. We have had 2 exchange visits and will plan to continue our work beyond the grant
Collaborator Contribution They have provided patient data and samples which we will process in Manchester and we have also trained some local lab staff to do some of the biomarkers in Rio
Impact none to date
Start Year 2015
 
Description 16th International Congress on Antiphospholipid Antibodies; Manchester Sept 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I organised this conference in Manchester
It included scientific presentations, state-of-the-art updates
We also had a patient engagement and education day that included educational talks and agenda setting activities (50 patients or carers attended)
Year(s) Of Engagement Activity 2019
 
Description Kellgren @ 10 Manchester (December 2017, Manchester) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact This event was to update our patients and study participants on our research and progress with recent studies
Year(s) Of Engagement Activity 2017
 
Description Lupus Foundation of America Improving access to healthcare workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact The Lupus Foundation of America have initiated the APLHA project to identify gaps in improving care for SLE patients
I am one of only 4 non-US experts on this global advisory board
Year(s) Of Engagement Activity 2020
 
Description Maternal Medicine Symposium, Manchester - June 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This RCPE training day was on maternal medicine and I presented talk on pregnancy in SLE.
Year(s) Of Engagement Activity 2018
 
Description SLE presentation to Red Ex Pharmaceuticals 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact I gave a presentation to this NW-based SME to discuss stratified medicine and chronic damage in SLE patients
Year(s) Of Engagement Activity 2018
 
Description Talk at the BBC Breakfast Show (September 2017) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I spoke on BBC Breakfast about SLE following Selena Gomez's renal transplant. This provided huge publicity for SLE and widened awareness
Year(s) Of Engagement Activity 2017
 
Description Visit to China to key universities (January 2018, China) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Our university visited 4 Chinese universities. We planned and discussed future collaborations including student exchanges, collaborative grants and future visits
Year(s) Of Engagement Activity 2018