COVID-19 mRNA vaccine-associated autoimmunity presenting as minimal change disease and membranous nephropathy

ABSTRACT

Background: Vaccine-triggered complications, including autoimmune diseases and minimal change disease (MCD), were reported during recent COVID-19 vaccine rollout. Anti-nephrin autoantibodies were described in nephrotic syndrome (NS) with kidney biopsy (Kbx)-proven MCD. Therefore, we examined patients with COVID-19 vaccineassociated NS for anti-nephrin autoantibodies. Methods: 5 patients presenting with nephrotic-range proteinuria 1-3 weeks after COVID-19 vaccine and a KBx were identified (3 Pfizer/BioNTech, 2 Moderna). Past medical history and lab tests including serum creatinine (sCr), urine protein-to-creatinine ratio (UPCR), and serological workup were recorded. KBx were routinely evaluated by light microscopy (LM), immunofluorescence microscopy (IF), and electron microscopy (EM), followed by confocal examination of relative IgG and nephrin localization in all patients;serological studies for anti-nephrin antibodies using human glomerular extract and recombinant nephrin extracellular domain were performed using plasma available on 2 patients. Results: In all patients, sCr was 0.5-1.2 mg/dl and UPCR 4.5-7.6 g/g. 1 patient had MCD in remission diagnosed 6 months prior;others had no relevant PMH. All workup was negative, except low positive ANA in 2 patients. On KBx, diagnosis of MCD was made in 4 and stage I membranous nephropathy (MN) in 1 patient(s) (serum albumin 2.0-2.4g/dl in MCD and 3.6g/dl in MN patient(s));all had mild chronic changes. All 4 MCD patients had fine granular punctate podocyte staining for polyclonal IgG colocalizing with nephrin by IF and diffuse FPE by EM;in 1 patient plasma was saved during NS and was serologically positive for anti-nephrin. The MN patient had 3+ fine granular IF staining for polyclonal IgG and PLA2r along GBMs with sparse superficial subepithelial electron-dense deposits on EM, and was serologically negative for antinephrin. All MCD patients were successfully treated with oral glucocorticoids, while the MN patient was monitored closely under RAAS blockage. Conclusions: COVID-19 mRNA vaccines can trigger de-novo or relapsing anti-nephrin-and PLA2r-mediated NS, thus adding both autoimmune-mediated podocytopathies to vaccine-induced complications. Temporal association is essential for diagnosis;prompt accurate diagnosis benefits treatment and response.