New-onset systemic lupus erythematosus beginning as class V lupus nephritis after COVID-19 vaccination
Authors: María Fernanda Zavala-Miranda, Samantha G. González-Ibarra, Abril A. Pérez-Arias, Norma O. Uribe-Uribe, Juan M. Mejia-Vilet
Journal: Kidney International (2021)

We read the report by Tuschen et al. of a 42-year-old woman with a previous diagnosis of systemic lupus erythematosus (SLE) and class V lupus nephritis (LN) that developed a flare 1 week after vaccination with the mRNA coronavirus disease 2019 (COVID-19) vaccine BNT162b2 (Pfizer–BioNTech).1Tuschen K. Bräsen J.H. Schmitz J. et al.Relapse of class V lupus nephritis after vaccination with COVID-19 mRNA vaccine.Kidney Int. 2021; 100: 941-944Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Here, we report a case of a 23-year-old woman who presented with nephrotic syndrome 1 week after vaccination with the first dose of the AZD1222 (ChAdOx1-S) nCoV-19 vaccine (AstraZeneca). She had no previous medical history of disease and was taking no medications. She had not been previously infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Her family history was negative for autoimmune diseases. On July 21, 2021, she was vaccinated, without major adverse events. One week later, she developed abrupt eyelid edema and foamy urine that progressed to anasarca within days. She also experienced hair loss. Physical examination showed normal blood pressure and pitting edema up to the thighs. Her laboratory tests showed lymphopenia (1000 × 103/ml), a serum creatinine level of 0.8 mg/dl (estimated glomerular filtration rate of 104 ml/min per 1.73 m2), a serum albumin level of 1.57 g/dl, a total cholesterol level of 351 mg/dl, proteinuria of 12.6 g/24 h (protein-to-creatinine ratio of 11.0 mg/mg), a complement C3 level of 85 mg/dl (reference, 87–200 mg/dl), and a C4 level of 12 mg/dl (reference, 19–52 mg/dl). Antinuclear antibody (ANA) titer was a 1:1280 homogeneous pattern; the anti-dsDNA-IgG level was 17.1 IU/ml; and antiphospholipid antibody panel was negative. Serology for SARS-CoV-2 demonstrated negative IgM and IgG antibodies to the nucleocapsid antigen (NCP), suggesting no previous infection by this virus. Anti–SARS-CoV-2–Spike IgG antibodies in response to vaccination were quantified at 32.8 UI/ml (reference, <1 UI/ml), suggesting an appropriate response to vaccination. The kidney biopsy performed 1 week after the start of symptoms (2 weeks post-vaccination) demonstrated secondary membranous nephropathy, with diffuse thickening of the basement glomerular membrane and mild mesangial expansion. One of 13 glomeruli had sclerosis, and interstitial fibrosis was less than 10%, with no tubular atrophy, and normal vessels. Direct immunofluorescence revealed deposits of IgG, IgM, C1q, C3c, kappa, and lambda chains in the subepithelial and mesangial space. Electron microscopy showed mesangial and subepithelial electron-dense deposits (Figure 1). A diagnosis of SLE with class V LN was established. We started treatment with mycophenolate mofetil, high-dose glucocorticoids, hydroxychloroquine, and diuretics. After 3 weeks of follow-up, edema has improved and the patient continues follow-up. Diverse glomerular diseases have been reported in association with COVID-19 vaccination, particularly podocytopathies, IgA nephropathy, and anti-neutrophil cytoplasmic antibody (ANCA) vasculitis.2Bomback A.S. Kudose S. D'Agati V.D. De novo and relapsing glomerular diseases after COVID-19 vaccination: What do we know so far?.Am J Kidney Dis. 2021; 78: 477-480Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar For SLE, the Vaccination Against COVID in Systemic Lupus (VACOLUP) study3Felten R. Kawka L. Dubois M. et al.Tolerance of COVID-19 vaccination in patients with systemic lupus erythematosus: the international VACOLUP study.Lancet Rheumatol. 2021; 3: e613-e615Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar reported 2 renal flares (with no specification of the type of LN), and the report by Tuschen et al.1Tuschen K. Bräsen J.H. Schmitz J. et al.Relapse of class V lupus nephritis after vaccination with COVID-19 mRNA vaccine.Kidney Int. 2021; 100: 941-944Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar also corresponded to a class V LN flare. In animal models, the loss of the T-helper type 1 (Th1)/T-helper type 2 (Th2) balance is crucial for the development of LN, and may even determine the phenotype of the glomerulonephritis.4Suárez-Fueyo A. Bradley S.J. Klatzmann D. Tsokos G.C. T-cells and autoimmune kidney disease.Nat Rev Nephrol. 2017; 13: 329-343Crossref PubMed Scopus (93) Google Scholar For example, the lack of the WSX-1 gene in the MRL/lpr SLE mice model increases both the Th2 response, with increased interleukin-4, and the development of a disease resembling human membranous nephropathy with IgG1-dominant electro-dense deposits in the subepithelial space.5Shimizu S. Sugiyama N. Masutani K. et al.Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1).J Immunol. 2005; 175: 7185-7192Crossref PubMed Scopus (97) Google Scholar Moreover, the Th1 response has been associated with the development of LN proliferative variants.6Masutani K. Akahoshi M. Tsuruya K. et al.Predominance of Th1 immune response in diffuse proliferative lupus nephritis.Arthritis Rheum. 2001; 44: 2097-2106Crossref PubMed Scopus (216) Google Scholar T cells are key to stimulating the immune response to vaccination. From phase 1 and 2 trials of the AZD1222 nCoV-19 vaccine, it has been shown that the spike-specific effector T-cell response presents early, from day 8 post-vaccination through day 56.7Ledford H. Could mixing COVID vaccines boost immune response?.Nature. 2021; 590: 375-376Crossref PubMed Scopus (44) Google Scholar There is a robust Th1 response with an expansion of CD8+ T cells, with increases in cytokines such as tumor necrosis factor, interleukin-2, and interferon gamma. However, no Th2 response has been found after AZD1222 nCoV-19 vaccination.8Swanson P.A. Padilla M. Hoyland W. et al.T-cell mediated immunity after AZD1222 vaccination: a polyfunctional spike-specific Th1 response with a diverse TCR repertoire.medRxiv. 2021; https://doi.org/10.1101/2021.06.17.21259027Crossref Scopus (0) Google Scholar Until now, there are no mechanisms or triggers to support a direct causal relationship between COVID-19 vaccination and SLE flares.9Tang W. Askanase A.D. Khalili L. Merrill J.T. SARS-CoV-2 vaccines in patients with SLE.Lupus Sci Med. 2021; 8e000479Crossref PubMed Scopus (28) Google Scholar In this case, it is plausible that the immune response elicited by vaccination elicited SLE emergence in an immunologically predisposed individual. Patients with SLE after vaccination need to be closely followed, and post-vaccination events need to be registered in multinational registries.3Felten R. Kawka L. Dubois M. et al.Tolerance of COVID-19 vaccination in patients with systemic lupus erythematosus: the international VACOLUP study.Lancet Rheumatol. 2021; 3: e613-e615Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar Relapse of class V lupus nephritis after vaccination with COVID-19 mRNA vaccineKidney InternationalVol. 100Issue 4PreviewSeveral of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines use an mRNA lipid nanoparticle-encapsulated platform. In experimental models, the induced antibody titers are higher, and T- and B-cell responses are enhanced, compared to the level with traditional vaccines. Possibly, due to this higher efficacy, more and more kidney-specific side effects of mRNA vaccines related to immune-mediated glomerular disease are being reported.1–3 Because of similar type I interferon and proinflammatory cytokine pathways in systemic lupus erythematodes and coronavirus disease 2019 (COVID-19), either potentiated or dysregulated immune responses to SARS-CoV-2 vaccines can be suspected to trigger disease activity in previously stable lupus. Full-Text PDF New-onset class III lupus nephritis with multi-organ involvement after COVID-19 vaccinationKidney InternationalVol. 101Issue 4PreviewVaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger an autoimmune response. Two cases of lupus nephritis after the administration of the mRNA vaccine (BNT162b2, Pfizer–BioNTech) and the adenoviral vector vaccine (AZD1222 [ChAdOx1-S], AstraZeneca) have been reported.1,2 We present a case of lupus nephritis with multi-organ involvement after the administration of the AZD1222 vaccine. Full-Text PDF