New-onset class III lupus nephritis with multi-organ involvement after COVID-19 vaccination

To the editor:

Vaccination 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.

In 2015, a 60-year-old woman was treated with oral corticosteroids for a skin rash at a private dermatologic clinic. The rash was an itchy, brownish skin lesion with erythematous macular patches on both medial malleolar areas. At that time, she was told she might have an autoimmune disease, based on a positive test result for antinuclear antibody, but further detailed tests for autoantibodies were not done. Blood and dipstick urine tests showed a serum creatinine level of 0.66 mg/dl and negative results for protein and blood. A skin biopsy was not performed. The skin lesion resolved promptly, and she had not visited the hospital thereafter. She had no prior coronavirus disease 2019 (COVID-19) infection and no other medical disease. She had not been on any medications. She had received flu shots every year without health problems. On June 30, 2021, she underwent a general health checkup, which showed a serum creatinine level of 0.74 mg/dl and negative urine test results. Following the second dose of 0.5 ml of COVID-19 vaccine on August 31, she became asthenic and did not eat well. Her symptoms worsened, and she developed foamy urine in late October. Physical examination revealed bilateral pitting edema and a body temperature of 38.7 °C. Her nasopharyngeal COVID-19 polymerase chain reaction test was negative. A neutralizing antibody test with chemiluminescent immunoassay (Siemens Healthineers, Erlangen, Germany) was positive for the SARS-CoV-2 S protein (>75 Index). Laboratory tests showed lymphopenia, anemia, and thrombocytopenia. Her serum creatinine level was 1.81mg/dl, and the spot urine protein-to-creatinine ratio was 4.82 g/g, with many dysmorphic red blood cells. C3 and C4 levels were 19.5 and 4.30 mg/dl, respectively, and she had an antinuclear antibody ratio of 1:1280, anti-double stranded DNA of >379 IU/ml, and positive results for anti-smith antibody. A kidney biopsy demonstrated class III lupus nephritis. Light microscopy identified 16 glomeruli, of which 7 showed endocapillary hypercellularity, 2 cellular crescents, and wire loop lesions (Figure 1 a). Immunofluorescence revealed a typical “full-house” pattern (Figure 1b). Electron microscopy confirmed electron-dense deposits (Figure 1c). A chest computed tomography scan showed patchy, nodular consolidations (Figure 1d). A cotton wool spot lesion was seen on funduscopic examination (Figure 1f).

Figure 1.

Representative micrographs from the kidney biopsy. (a) Light microscopy shows endocapillary hypercellularity with wire loop formation (periodic acid–Schiff stain; bar = 50 μm). (b) A representative image of positive C1a staining (bar = 50 μm). Direct immunofluorescence also identified other deposits of IgG, IgA, IgM, C3, C4, C1q, kappa, and lambda chains along the peripheral capillary wall and in the mesangium. (c) Electron microscopy shows subendothelial capillary wall immune deposits and a few small subepithelial electron-dense deposits (bar = 10 μm). Chest computed tomography (d) at the time of admission and (e) after immunosuppressive treatment. (f) A cotton wool spot (white arrow) found on the right eye. OD, oculus dexter. To optimize viewing of this image, please see the online version of this article at www.kidney-international.org.

We started treatment with i.v. pulse methylprednisolone (15 mg/kg for 3 consecutive days) and i.v. cyclophosphamide (500 mg biweekly) followed by oral prednisolone (1 mg/kg) and hydroxychloroquine (100 mg bid). Ten days after treatment, her serum creatinine and urine protein-to-creatinine ratio levels decreased to 0.93 mg/dl and 1.64 g/g, respectively. A repeat chest computed tomography scan showed a marked resolution of consolidations (Figure 1e).

The incidence of glomerulonephritis, including minimal change disease, membranous nephropathy, and IgA nephropathy, after COVID-19 vaccination has been increasing. The AZD1222 vaccine can induce Th1 responses with an expansion of CD8+ T cells and enhance cytokine production. A hypothesis for why this happens is that cross-reactivity occurs between antibodies against the SARS-CoV-2 S protein and different tissue antigens, leading to autoimmune diseases.^{3 , 4} Thus, we believe that the COVID-19 vaccine was a key trigger that elicited an autoimmune response and the development of lupus nephritis in our patient.

Disclosure

All the authors declared no competing interests.