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Article ; Online: Foreword: Preventing COVID-19 Among the Immunocompromised Population.

Willicombe, Michelle

2023 Volume 228, Issue Suppl 1, Page(s) S1–S3

Abstract: The COVID-19 pandemic represented 1 of the more significant and unique public health challenges facing the global community, particularly afflicting those with compromised immune systems. These immunocompromised individuals were readily recognized as a ... ...

Abstract	The COVID-19 pandemic represented 1 of the more significant and unique public health challenges facing the global community, particularly afflicting those with compromised immune systems. These immunocompromised individuals were readily recognized as a group at high risk of infection by SARS-CoV-2 and the associated severe outcomes of COVID-19. Although preventive strategies such as vaccination are important, initial clinical vaccine trials did not enroll immunocompromised individuals; in-depth evaluations of the safety, immunogenicity, and real-world outcomes associated with these vaccines were conducted in this population thereafter. As immunogenicity data of COVID-19 vaccination among this disparate group of individuals emerged, vaccination strategies were adapted to address outstanding challenges and further protect the entirety of this population. This 8-part journal supplement characterizes in-depth the mRNA-based COVID-19 vaccination strategies across the spectrum of immunocompromised individuals, focusing on the ongoing approaches to challenges facing this group as the pandemic continues to evolve.
MeSH term(s)	Humans ; COVID-19/prevention & control ; SARS-CoV-2 ; COVID-19 Vaccines ; Pandemics/prevention & control ; Dietary Supplements ; Vaccination
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2023-08-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad106
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Article ; Online: SARS-CoV-2 vaccine strategies in kidney transplant recipients.

Prendecki, Maria / Willicombe, Michelle

The Lancet. Infectious diseases

2022 Volume 23, Issue 3, Page(s) 263–264

MeSH term(s)	Humans ; COVID-19 Vaccines ; Kidney Transplantation ; COVID-19 ; SARS-CoV-2 ; Antibodies, Viral
Chemical Substances	COVID-19 Vaccines ; Antibodies, Viral
Language	English
Publishing date	2022-10-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(22)00666-1
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Zs.A 5743: Show issues

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Article ; Online: Single-dose SARS-CoV-2 vaccination efficacy in the elderly.

Prendecki, Maria / Willicombe, Michelle

The Lancet. Infectious diseases

2021 Volume 21, Issue 11, Page(s) 1474–1475

MeSH term(s)	Aged ; COVID-19 ; COVID-19 Vaccines ; Humans ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Vaccination
Chemical Substances	COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2021-06-23
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(21)00354-6
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Article ; Online: Application of HLA molecular level mismatching in ethnically diverse kidney transplant recipients receiving a steroid-sparing immunosuppression protocol.

Santos, Eva / Spensley, Katrina / Gunby, Nicola / Worthington, Judith / Roufosse, Candice / Anand, Arthi / Willicombe, Michelle

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2024

Abstract: Defining HLA mismatch at the molecular compared with the antigen level has been shown to be superior in predicting alloimmune responses, although data from across different patient populations are lacking. Using HLA-Matchmaker, HLA-EMMA and PIRCHE-II, ... ...

Abstract	Defining HLA mismatch at the molecular compared with the antigen level has been shown to be superior in predicting alloimmune responses, although data from across different patient populations are lacking. Using HLA-Matchmaker, HLA-EMMA and PIRCHE-II, this study reports on the association between molecular mismatch (MolMM) and de novo donor-specific antibody (dnDSA) in an ethnically diverse kidney transplant population receiving a steroid-sparing immunosuppression protocol. Of the 419 patients, 51 (12.2%) patients had dnDSA. De novo DSA were seen more frequently with males, primary transplants, patients receiving tacrolimus monotherapy, and unfavorably HLA-matched transplants. There was a strong correlation between MolMM load and antigen mismatch, although significant variation of MolMM load existed at each antigen mismatch. MolMM loads differed significantly by recipient ethnicity, although ethnicity alone was not associated with dnDSA. On multivariate analysis, increasing MolMM loads associated with dnDSA, whereas antigen mismatch did not. De novo DSA against 8 specific epitopes occurred at high frequency; of the 51 patients, 47 (92.1%) patients with dnDSA underwent a pretreatment biopsy, with 21 (44.7%) having evidence of alloimmune injury. MolMM has higher specificity than antigen mismatching at identifying recipients who are at low risk of dnDSA while receiving minimalist immunosuppression. Immunogenicity consideration is important, with more work needed on identification, especially across different ethnic groups.
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1016/j.ajt.2024.02.019
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Article ; Online: Should we be clinically assessing antibody responses to covid vaccines in immunocompromised people?

Willicombe, Michelle / Scanlon, Miranda / Loud, Fiona / Lightstone, Liz

BMJ (Clinical research ed.)

2022 Volume 377, Page(s) o966

MeSH term(s)	Antibodies, Viral ; Antibody Formation ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Immunocompromised Host ; Vaccines
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; Vaccines
Language	English
Publishing date	2022-04-12
Publishing country	England
Document type	Journal Article
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj.o966
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Article ; Online: COVID-19 vaccination in patients with immunity-mediated kidney disease.

Prendecki, Maria / Willicombe, Michelle / McAdoo, Stephen P

Nature reviews. Nephrology

2021 Volume 17, Issue 12, Page(s) 790–791

MeSH term(s)	COVID-19/prevention & control ; COVID-19 Vaccines/administration & dosage ; Humans ; Kidney Diseases/immunology ; Vaccination
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2021-10-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2490366-8
ISSN	1759-507X ; 1759-5061
ISSN (online)	1759-507X
ISSN	1759-5061
DOI	10.1038/s41581-021-00502-7
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Zs.A 6334: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Steroid Sparing Maintenance Immunosuppression in Highly Sensitised Patients Receiving Alemtuzumab Induction.

Santos, Eva / Spensley, Katrina / Gunby, Nicola / Clarke, Candice / Anand, Arthi / Roufosse, Candice / Willicombe, Michelle

Transplant international : official journal of the European Society for Organ Transplantation

2023 Volume 36, Page(s) 11056

Abstract: This analysis reports on the outcomes of two different steroid sparing immunosuppression protocols used in the management of 120 highly sensitised patients (HSPs) with cRF>85% receiving Alemtuzumab induction, 53 maintained on tacrolimus (FK) monotherapy ... ...

Abstract	This analysis reports on the outcomes of two different steroid sparing immunosuppression protocols used in the management of 120 highly sensitised patients (HSPs) with cRF>85% receiving Alemtuzumab induction, 53 maintained on tacrolimus (FK) monotherapy and 67 tacrolimus plus mycophenolate mofetil (FK + MMF). There was no difference in the median cRF or mode of sensitisation between the two groups, although the FK + MMF cohort received more poorly matched grafts. There was no difference in one-year patient or allograft survival, however rejection free survival was inferior with FK monotherapy compared with FK + MMF at 65.4% and 91.4% respectively,
MeSH term(s)	Humans ; Alemtuzumab/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Tacrolimus/therapeutic use ; Kidney Transplantation/methods ; Immunosuppression Therapy/methods ; Steroids ; Mycophenolic Acid/therapeutic use ; Graft Rejection/prevention & control ; Graft Survival
Chemical Substances	Alemtuzumab (3A189DH42V) ; Immunosuppressive Agents ; Tacrolimus (WM0HAQ4WNM) ; Steroids ; Mycophenolic Acid (HU9DX48N0T)
Language	English
Publishing date	2023-06-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.3389/ti.2023.11056
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Article ; Online: Frailty and the psychosocial components of the edmonton frail scale are most associated with patient experience in older kidney transplant candidates - a secondary analysis within the kidney transplantation in older people (KTOP) study.

Thind, Amarpreet K / Levy, Shuli / Wellsted, David / Willicombe, Michelle / Brown, Edwina A

Frontiers in nephrology

2023 Volume 2, Page(s) 1058765

Abstract: Background: Older people with end-stage kidney disease (ESKD) are vulnerable to frailty, which impacts on clinical and experiential outcomes. With kidney transplantation in older people increasing, a better understanding of patient experiences is ... ...

Abstract	Background: Older people with end-stage kidney disease (ESKD) are vulnerable to frailty, which impacts on clinical and experiential outcomes. With kidney transplantation in older people increasing, a better understanding of patient experiences is necessary for guiding decision making. The Kidney Transplantation in Older People (KTOP):impact of frailty on outcomes study aims to explore this. We present a secondary analysis of the Edmonton Frail Scale (EFS) and its relationship with patient experience scores. Methods: The KTOP study is a single centre, prospective study, which began in October 2019. All ESKD patients aged ≥60 considered for transplantation at Imperial College Renal and Transplant Centre were eligible. Frailty was assessed using the EFS and 5 questionnaires assessed patient experience and quality of life (QoL) (Short Form-12(v2), Palliative Care Outcome Scale-Symptoms Renal, Depression Patient Health Questionnaire-9, Illness Intrusiveness Ratings Scale, Renal Treatment Satisfaction Questionnaire). The EFS was divided into 4 subdomains (psychosocial, physical function, medical status, and general health) and then compared with the questionnaire scores. Results: 210 patients have been recruited (aged 60-78), 186 of whom completed EFS assessments. 118 (63.4%) participants were not frail, 36 (19.4%) vulnerable, and 32 (17.2%) were frail. Worse frailty scores were associated with poorer patient experience and QoL scores across all questionnaires. Severe deficits in the EFS psychosocial subdomain showed a statistically significant association with higher depression screen scores (coefficient 4.9, 95% CI 3.22 to 6.59), lower physical (coefficient -4.35, 95% CI -7.59 to -1.12) and mental function scores (coefficient -8.33, 95% CI -11.77 to -4.88) from the Short Form-12(v2), and lower renal treatment satisfaction scores (coefficient -5.54, 95% CI -10.70 to -0.37). Deficits in the physical function and medical status EFS subdomians showed some association with patient experience scores. Conclusion: In the KTOP study cohort at recruitment vulnerable and frail candidates reported worse QoL and patient experiences. Severe deficits in the psychosocial subdomains of the EFS showed a strong association with patient experience and QoL, whilst physical function and medical status deficits showed a lesser association. This has highlighted specific EFS domains that may be suitable for targeted interventions to improve experiences and optimise outcomes.
Language	English
Publishing date	2023-01-17
Publishing country	Switzerland
Document type	Journal Article
ISSN	2813-0626
ISSN (online)	2813-0626
DOI	10.3389/fneph.2022.1058765
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Article ; Online: COVID-19 and Calcineurin Inhibitors: Should They Get Left Out in the Storm?

Willicombe, Michelle / Thomas, David / McAdoo, Stephen

Journal of the American Society of Nephrology : JASN

2020 Volume 31, Issue 6, Page(s) 1145–1146

MeSH term(s)	Betacoronavirus/drug effects ; COVID-19 ; Calcineurin Inhibitors/pharmacology ; Coronavirus Infections/complications ; Coronavirus Infections/immunology ; Humans ; Immunosuppressive Agents/pharmacology ; Organ Transplantation ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/immunology ; SARS-CoV-2
Chemical Substances	Calcineurin Inhibitors ; Immunosuppressive Agents
Keywords	covid19
Language	English
Publishing date	2020-04-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2020030348
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Article ; Online: Application of the Banff Human Organ Transplant Panel to kidney transplant biopsies with features suspicious for antibody-mediated rejection.

Beadle, Jack / Papadaki, Artemis / Toulza, Frederic / Santos, Eva / Willicombe, Michelle / McLean, Adam / Peters, James / Roufosse, Candice

Kidney international

2023 Volume 104, Issue 3, Page(s) 526–541

Abstract: The Banff Classification for Allograft Pathology includes the use of gene expression in the diagnosis of antibody-mediated rejection (AMR) of kidney transplants, but a predictive set of genes for classifying biopsies with 'incomplete' phenotypes has not ... ...

Abstract	The Banff Classification for Allograft Pathology includes the use of gene expression in the diagnosis of antibody-mediated rejection (AMR) of kidney transplants, but a predictive set of genes for classifying biopsies with 'incomplete' phenotypes has not yet been studied. Here, we developed and assessed a gene score that, when applied to biopsies with features of AMR, would identify cases with a higher risk of allograft loss. To do this, RNA was extracted from a continuous retrospective cohort of 349 biopsies randomized 2:1 to include 220 biopsies in a discovery cohort and 129 biopsies in a validation cohort. The biopsies were divided into three groups: 31 that fulfilled the 2019 Banff Criteria for active AMR, 50 with histological features of AMR but not meeting the full criteria (Suspicious-AMR), and 269 with no features of active AMR (No-AMR). Gene expression analysis using the 770 gene Banff Human Organ Transplant NanoString panel was carried out with LASSO Regression performed to identify a parsimonious set of genes predictive of AMR. We identified a nine gene score that was highly predictive of active AMR (accuracy 0.92 in the validation cohort) and was strongly correlated with histological features of AMR. In biopsies suspicious for AMR, our gene score was strongly associated with risk of allograft loss and independently associated with allograft loss in multivariable analysis. Thus, we show that a gene expression signature in kidney allograft biopsy samples can help classify biopsies with incomplete AMR phenotypes into groups that correlate strongly with histological features and outcomes.
MeSH term(s)	Humans ; Antibodies ; Biopsy ; Graft Rejection/diagnosis ; Graft Rejection/genetics ; Graft Rejection/pathology ; Kidney Transplantation/adverse effects ; Retrospective Studies
Chemical Substances	Antibodies
Language	English
Publishing date	2023-05-11
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2023.04.015
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