Relapse of IgG4-related nephritis following mRNA COVID-19 vaccine
Authors: Christophe Masset, Delphine Kervella, Christine Kandel-Aznar, Aurélie Fantou, Gilles Blancho, Mohamed Hamidou
Journal: Kidney International (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is currently recommended for patients with chronic kidney disease and immunocompromised patients because their risk of developing severe forms of coronavirus disease 2019 (COVID-19) is higher than other patients. Several reports have highlighted the increased risk of immune disease recurrence following mRNA vaccination, including minimal change disease, membranous nephropathy, or even acute allograft rejection.1Kervella D. Jacquemont L. Chapelet-Debout A. et al.Minimal change disease relapse following SARS-CoV2 mRNA vaccine.Kidney Int. 2021; 100: 457-458Abstract Full Text Full Text PDF Scopus (38) Google Scholar,2Aydın M.F. Yıldız A. Oruç A. et al.Relapse of primary membranous nephropathy after inactivated SARS-CoV-2 virus vaccination.Kidney Int. 2021; 100: 464-465Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar We report the case of a 66-year-old man who was diagnosed with IgG4-related disease (IgG4-RD) nephritis in December 2019. At this time, he presented with asthenia associated with acute kidney injury, evaluated by serum creatininemia (SCr) at 450 μmol/L and aseptic leukocyturia (120/mm3) without proteinuria or hematuria. Although anti-DNA antibodies were negative, anti–SSA-52 antibodies were highly positive (113 UI/L; normal range, <10 UI/L) and were associated with hypocomplementemia C3 (0.51 g/L; normal range, 0.9–1.8 g/L) and C4 (<0.02 g/L; normal range, 0.1–0.4 g/L). Serum IgG4 antibodies were elevated at 6.9 g/L (normal range, 0.03–2.01 g/L). A positron emission tomographic scan revealed intense bilateral kidney fixation and fat infiltration. A kidney biopsy revealed IgG4-related nephritis with storiform fibrosis and an IgG4-to-IgG ratio >40 (Figure 1). Initial treatment consisted of steroids (1 mg/kg), quickly followed by 4 weekly rituximab perfusions (375 mg/m2) due to steroid resistance.3Ebbo M. Grados A. Samson M. et al.Long-term efficacy and safety of rituximab in IgG4-related disease: data from a French nationwide study of thirty-three patients.PLoS One. 2017; 12e0183844Crossref PubMed Scopus (149) Google Scholar Kidney function improved, along with a decrease in SCr to 180 μmol/L, disappearance of leukocyturia, and normalization of serum complement and IgG4 levels, permitting steroid withdrawal. Anti–SSA-52 antibodies also strongly decreased and became negative in June 2020. A positron emission tomographic scan was performed on January 18, 2021, for IgG4-RD follow-up, and showed no pathologic fixation nor renal infiltration. The patient was vaccinated with an mRNA vaccine (BNT162b2 mRNA; Pfizer BioNTech) on January 28, 2021, and February 17, 2021. Two weeks later, he presented with intense asthenia with arthralgias and myalgias. SCr was elevated at 210 μmol/L on March 5, 2021, increased to 250 μmol/L on March 22, 2021, and was associated with recurrence of aseptic leukocyturia. Anti–SSA-52 levels increased from 4 to 17 UI/L. SARS-CoV-2 serology was positive for anti–spike protein at 177 UI/L (electrochemiluminescence immunoassay, Roche Elecsys). Steroid therapy was initiated at 0.5 mg/kg and associated with rituximab perfusion (500 mg), allowing a quick improvement of the general symptoms and resolution of acute kidney injury. Anti–SSA-52 levels also decreased to 12 UI/L by May 2021 (Figure 2).Figure 2Evolution of sera creatininemia (SCr) and anti–SSA-52 antibodies, reflecting the activity of IgG4-related disease, from the diagnosis in December 2019 to the relapse in March 2021 following mRNA coronavirus disease 2019 (COVID-19) vaccine. RTX, rituximab.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Our report highlights the possibility of immune disease relapse following mRNA vaccine, a situation previously described by others. It is currently unknown if immune disease recurrence is linked to direct immune activation following vaccination, chronic immune activation following a paucisymptomatic allergic reaction, or both. Indeed, IgG4-RD pathogenesis has been linked to IgE production, as seen in late immune-mediated allergic reactions.4Perugino C.A. Stone J.H. IgG4-related disease: an update on pathophysiology and implications for clinical care.Nat Rev Rheumatol. 2020; 16: 702-714Crossref PubMed Scopus (175) Google Scholar If the benefit-to-risk ratio indisputably favors vaccination of this at-risk population, physicians should be aware of the possibility of immune disease recurrence to provide close monitoring of these patients and fast treatment of relapses to avoid long-term consequences and progression to end-stage renal disease. Relapse of primary membranous nephropathy after inactivated SARS-CoV-2 virus vaccinationKidney InternationalVol. 100Issue 2PreviewCoronavirus disease 2019 (COVID-19) vaccine is one of the most effective public health interventions to end the COVID-19 outbreak. There are insufficient data on the use of COVID-19 vaccines in patients with autoimmune disease, but vaccines appear to be safe, and experience from previous vaccine studies does not indicate an increased risk of relapse/recurrence.1 However, theoretically, unwanted immunologic events, such as autoimmunity, may be triggered by vaccines. We describe a patient with membranous nephropathy (MN) who stayed in remission for 8 years and experienced a relapse after vaccination with a purified inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus vaccine called CoronaVac (produced in China by Sinovac). Full-Text PDF Minimal change disease relapse following SARS-CoV-2 mRNA vaccineKidney InternationalVol. 100Issue 2PreviewAlthough the pathogenesis of minimal change disease (MCD) has not yet been clearly elucidated, immune dysregulation is probable,1 and the risk of relapse after the administration of various vaccines (especially meningococcal C conjugate vaccines) has been suggested.2,3 Here, we report a case of MCD relapse following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Full-Text PDF Granulomatous vasculitis after the AstraZeneca anti–SARS-CoV-2 vaccineKidney InternationalVol. 100Issue 3PreviewSeveral reports of newly diagnosed or relapses of immune-mediated renal diseases following vaccination with anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA and AstraZeneca vaccines recently emerged in the litterature.1,2 Full-Text PDF COVID-19 vaccination followed by activation of glomerular diseases: does association equal causation?Kidney InternationalVol. 100Issue 5PreviewTo date, >4 billion doses of the various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been administered worldwide in response to the coronavirus disease 2019 (COVID-19) pandemic. Even as widespread vaccination campaigns have contributed to declining case rates, adverse events are appearing beyond those originally reported in the clinical trials of vaccine efficacy and safety. Of particular relevance to the kidney is the increasing number of reports of de novo or reactivation of glomerular diseases (Table 11–25). Full-Text PDF