Work

Anti‐HLA and anti‐SARS‐CoV‐2 antibodies in kidney transplant recipients with COVID‐19

Year: 2021

Type: article

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its associated illness coronavirus disease 2019 (COVID-19) have severely affected organ transplant recipients, with all-cause mortality rates exceeding 20% [1, 2. Although no clear guidelines exist on how to adjust immunosuppression, most centers reduce anti-rejection drugs to facilitate the T- and B-cell response against the virus. However, this maneuver may unleash the anti-donor immune response as well. Even if immunosuppression is not modified, infection episodes per se promote a proinflammatory state that may lead to an increased risk of rejection or of anti-HLA antibody development [3. In most of the reports published so far, acute rejection episodes were uncommon during COVID-19 infection despite immunosuppression reduction [4. However, no study has formally addressed the relationship between COVID-19 and the development of anti-HLA antibodies. We recently showed that kidney transplant recipients with COVID-19 display a broad activation of B-cell subsets, together with detectable serum anti-SARS-CoV-2 IgM and IgG as early as 10 days after the onset of clinical symptoms [5, suggestive of a broad activation of the humoral response. Herein, we tested the hypothesis that COVID-19 associates with the development of anti-HLA antibodies in kidney transplant recipients. The transplant center of the Parma University Hospital, Parma, Italy, actively follows up approximately 800 kidney transplant recipients. From March 1 to December 2, 2020, 17 of these patients were diagnosed with symptomatic SARS-CoV-2 infection (confirmed by RT-PCR testing). Thirteen patients were admitted at Parma University Hospital, Parma, Italy, and four were followed up as outpatients. Fourteen patients survived for more than 30 days after admission, and 7 of them had available serum that was collected at 3 months postinfection. In our center, kidney transplant recipients undergo regular measurements of donor-specific antibodies (DSA) and panel-reactive antibodies (PRA) and all the seven included patients had their measurements done no more than three months prior to infection. We used the sera collected at 3 months postinfection to measure anti-HLA (by Luminex Technology, One Lambda) and anti-SARS-CoV-2 IgM and IgG antibodies (JusChek; Acro Biotech, Rancho Cucamonga, CA, USA). At diagnosis, all patients showed pneumonia and signs of systemic inflammations, such as elevated C-reactive protein (CRP), IL-6, and D-Dimer (Table 1). During COVID-19, six patients underwent reduction in immunosuppression that was resumed at discharge (Table 1). Two patients developed acute kidney injury, but serum creatinine fully recovered at 3 months after COVID-19 infection (Table 1). Contrary to our hypothesis, none of the patients developed anti-HLA antibodies, but all of them had detectable anti-SARS-CoV-2 IgM and IgG (Table 1). One patient (patient 2) had anti-donor antibodies before COVID-19, but neither their MFI nor their HLA specificities increased after COVID-19. Basiliximab Rituximab Basiliximab Rituximab COVID-19 pneumonia (CT lung involvement) Yes (25%) Yes (15%) Yes (5%) Yes (NA) Yes (NA) Yes (20%) Yes (35%) AKI during COVID-19 (peak s-creatinine mg/dl) Yes (2.1) No (2.2) No (0.8) No (1.3) No (1.7) No (1.0) Yes (3.2) Reduced (21) Reduced (28) Withdrawn (28) Withdrawn (10) Withdrawn (25) Withdrawn (67) Withdrawn (41) Withdrawn (40) Increased (28) Increased (28) Increased (28) Increased (15) Anti-A2, MFI: 4971 Anti-A2, MFI: 3987 To the best of our knowledge, this is the first series of patients with serial anti-HLA antibody measurements. Despite significant reduction in immunosuppression in most of our patients and a systemic proinflammatory state associated with COVID-19, no patients developed signs of increased alloimmune response. This finding is in line with prior evidence that COVID-19 does not associate with disease relapses even in patients with autoimmune conditions [6. The mechanisms behind this unexpected phenomenon are unknown and worth investigating. Our analysis is still preliminary, and we cannot exclude that COVID-19 does in fact increase the risk of DSA development. Although multiple series have reported a relatively low risk of acute rejection in kidney transplant recipients with COVID-19, careful monitoring of alloimmune response during COVID-19 should still be advised, especially in transplant recipients undergoing significant reduction in immunosuppressive therapy. PC is supported by NIH NIAID Grant 3U01AI063594-17S1. JSM receives research support from One Lambda/Thermo Fisher. The other authors of this manuscript declare no funding and no conflict of interest.

Source: Transplant International

DOI: 10.1111/tri.13829