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World J Meta-Anal. Jun 18, 2024; 12(2): 91264
Published online Jun 18, 2024. doi: 10.13105/wjma.v12.i2.91264
Development of donor specific antibodies after SARS-CoV-2 vaccination: What do we know so far?
Ahmed Daoud, Karim Soliman, Maria Aurora Posadas Salas, Sakshi Vaishnav, Genta Uehara, Ahmed Abdelkader, Tibor Fulop, Michael J Casey, Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, SC 29425, United States
Ahmed Daoud, Department of Medicine, Cairo University Medical School, Cairo 11211, Egypt
Karim Soliman, Department of Medicine, Medical Services, Ralph H. Johnson VA Medical Center, Charleston, SC 29425, United States
Tibor Fulop, Department of Medicine, Division of Nephrology, Medical Services, Ralph H. Johnson VA Medical Center, Charleston, SC 29425, United States
ORCID number: Ahmed Daoud (0000-0001-6311-3887); Maria Aurora Posadas Salas (0000-0001-7411-7154); Michael J Casey (0000-0003-1099-1189).
Author contributions: Daoud A designed and performed the research; Soliman K, Posadas Salas MA, Vaishnav S, Uehara G, Abdelkader A, Fulop T, and Casey MJ wrote the manuscript. All authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ahmed Daoud, MD, PhD, Doctor, Staff Physician, Department of Medicine, Division of Nephrology, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, United States. ahmed.daoud84@yahoo.com
Received: December 29, 2023
Revised: April 18, 2024
Accepted: June 7, 2024
Published online: June 18, 2024
Processing time: 167 Days and 23.7 Hours

Abstract

Vaccination against Coronavirus disease-19 (COVID-19) was pivotal to limit spread, morbidity and mortality. Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies (DSAs) or increase in mean fluorescence intensity (MFI) of pre-existing DSAs in kidney transplant recipients (KTRs). This study involved a detailed literature search through December 2nd, 2023 using PubMed as the primary database. The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords: "COVID-19", "SARS-CoV-2 Vaccination", "Kidney, Renal Transplant", and "Donor specific antibodies". The results from related studies were collated and analyzed. A total of 6 studies were identified, encompassing 460 KTRs vaccinated against COVID-19. Immunological responses were detected in 8 KTRs of which 5 had increased MFIs, 1 had de novo DSA, and 2 were categorized as either having de novo DSA or increased MFI. There were 48 KTRs with pre-existing DSAs prior to vaccination, but one study (Massa et al) did not report whether pre-existing DSAs were associated with post vaccination outcomes. Of the remaining 5 studies, 35 KTRs with pre-existing DSAs were identified of which 7 KTRs (20%) developed de novo DSAs or increased MFIs. Overall, no immunological response was detected in 452 (98.3%) KTRs. Our study affirms prior reports that COVID-19 vaccination is safe for KTRs, especially if there are no pre-existing DSAs. However, if KTRs have pre-existing DSAs, then an increased immunological risk may be present. These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.

Key Words: COVID-19, SARS-CoV-2 vaccination, Kidney, Renal transplant, Donor specific antibodies

Core Tip: Our aim was to find out whether vaccines against Coronavirus disease 2019 (COVID-19) lead to an immunological response stimulating the production of de novo donor specific antibodies (DSAs) or increase in mean fluorescence intensity of pre-existing DSAs in kidney transplant recipients. We did a detailed literature search through December 2, 2023 using PubMed as the primary database. We used the following keywords: COVID-19, severe acute respiratory syndrome-coronavirus-2 vaccination, Kidney, Renal transplant, and DSAs. The results from related studies were collated and analyzed.
INTRODUCTION

Vaccination against Severe acute respiratory syndrome–coronavirus–2 (SARS-CoV-2) was pivotal to limit spread, morbidity and mortality of Coronavirus disease-19 (COVID-19), ensuring a high rate of protective antibody formation in the general population[1,2]. Solid organ transplant recipients (SOTRs) are maintained on lifelong immunosuppression to reduce the risk of cellular and antibody mediated rejections. Unfortunately, immunosuppression therapy may also lead to increased COVID-19 mortality among SOTRs[3,4], Since the introduction of the vaccination programs against SARS-CoV-2, vaccinating immunocompromised patients, including SOTRs has been considered as a priority[5].

The presence of anti-human leukocytic antigen (anti-HLA) donor specific antibodies (DSAs) is associated with antibody mediated rejection[6,7]. Do vaccines against SARS-CoV-2 accentuate an immunological response stimulating the production of anti-HLA DSA in kidney transplant recipients (KTRs)?

To answer this question, we conducted a detailed literature review, using PubMed as the primary database, with the search being completed by December 2nd, 2023. The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords: "COVID-19", "SARS-CoV-2 Vaccine", "Kidney, Renal Transplant" and "Donor Specific Antibodies". The results from related studies were collated and analyzed.

We screened 15 manuscripts, and excluded the following

Six unrelated articles that were mainly discussing safety, efficacy and response to COVID vaccines in KTRs.

One article described DSA formation, but was confounded by KTRs being hospitalized with an active COVID-19 infection[8].

This left us with 2 case reports and 7 studies. Abu-Khader et al[9] reported a case of 42-year-old who developed de novo DSAs and de novo anti-HLA non-DSAs after first dose of mRNA based COVID vaccine. Kim et al[10] reported a successful ABO-incompatible living donor kidney transplant in a patient who developed class I DSAs after COVID-19 vaccination.

There were 6 studies evaluating the development of DSAs after COVID vaccination, encompassing 460 KTRs vaccinated against COVID-19. Immunological responses were detected in 8 KTRs of which 5 had increased mean fluorescence intensity (MFI), 1 had de novo DSA, and 2 were categorized as either having de novo DSA or increased MFI[11-15]. There were 48 KTRs with pre-existing DSAs prior to vaccination, but one study (Massa et al[16]) did not report whether pre-existing DSAs were associated with post vaccination outcomes. Of the remaining 5 studies, 35 KTRs with pre-existing DSAs were identified of which 7 KTRs (20%) developed de novo DSAs or increased MFIs (Table 1). Overall, no immunological response was detected in 452 (98.3%) KTRs.

Table 1 Immunological outcomes after coronavirus disease 2019 vaccination.
Ref.
Number of patients vaccinated
Number of patients with pre-existing DSAs before vaccination
Type of vaccine
Number of patients who developed de novo DSAs
Number of patients with pre-existing DSAs who developed new DSAs or increased MFI post-vaccine
McCune et al[11]1005Moderna 64
Pfizer 36		02 (Unreported whether new DSA or increased MFI)
Kueht et al[12]9616Moderna
Pfizer
J and J		05 (All had increased MFIs)
Al Jurdi et al[13]585Moderna
Pfizer		00
Russo et al[14]821Pfizer00
Nishida et al[15]638mRNA vaccine (Moderna and/or Pfizer)00
Massa et al[16]6113Pfizer1Not reported
Total4604817
DSAs: Donor specific antibodies; MFI: Mean fluorescence intensity.

The findings of these studies are summarized in Table 1.

CONCLUSION

In conclusion, our study affirms prior reports that COVID-19 vaccination is safe for KTRs, especially if there are no pre-existing DSAs. However, if KTRs have pre-existing DSAs, then an increased immunological risk may be present. These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Medicine, research and experimental

Country of origin: United States

Peer-review report’s classification

Scientific Quality: Grade B

Novelty: Grade B

Creativity or Innovation: Grade B

Scientific Significance: Grade B

P-Reviewer: Rodrigues RF, Brazil S-Editor: Liu H L-Editor: A P-Editor: Che XX

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