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• W3200535500 abstract "To 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 11Hanna C. Herrera Hernandez L.P. Bu L. et al.IgA nephropathy presenting as macroscopic hematuria in 2 pediatric patients after receiving the Pfizer COVID-19 vaccine.Kidney Int. 2021; 100: 705-706Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar, 2Kudose S. Friedmann P. Albajrami O. D’Agati V.D. Histologic correlates of gross hematuria following Moderna COVID-19 vaccine in patients with IgA nephropathy.Kidney Int. 2021; 100: 468-469Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 3Anderegg M.A. Liu M. Saganas C. et al.De novo vasculitis after mRNA-1273 (Moderna) vaccination.Kidney Int. 2021; 100: 474-476Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 4Negrea L. Rovin B.H. Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathy.Kidney Int. 2021; 99: 1487Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar, 5Perrin P. Bassand X. Benotmane I. Bouvier N. Gross hematuria following SARS-CoV-2 vaccination in patients with IgA nephropathy.Kidney Int. 2021; 100: 466-468Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar, 6Tan H.Z. Tan R.Y. Choo J.C.J. et al.Is COVID-19 vaccination unmasking glomerulonephritis?.Kidney Int. 2021; 100: 469-471Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 7Rahim S.E.G. Lin J.T. Wang J.C. A case of gross hematuria and IgA nephropathy flare-up following SARS-CoV-2 vaccination.Kidney Int. 2021; 100: 238Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 8Weijers J. Alvarez C. Hermans M.M.H. Post-vaccinal minimal change disease.Kidney Int. 2021; 100: 459-461Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 9Morlidge C. El-Kateb S. Jeevaratnam P. Thompson B. Relapse of minimal change disease following the AstraZeneca COVID-19 vaccine.Kidney Int. 2021; 100: 459Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar, 10D’Agati V.D. Kudose S. Bomback A.S. et al.Minimal change disease and acute kidney injury following the Pfizer-BioNTech COVID-19 vaccine.Kidney Int. 2021; 100: 461-463Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 11Schwotzer N. Kissling S. Fakhouri F. Letter regarding “Minimal change disease relapse following SARS-CoV-2 mRNA vaccine.”.Kidney Int. 2021; 100: 458-459Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 12Holzworth A. Couchot P. Cruz-Knight W. Brucculeri M. Minimal change disease following the Moderna mRNA-1273 SARS-CoV-2 vaccine.Kidney Int. 2021; 100: 463-464Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 13Kervella D. Jacquemont L. Chapelet-Debout A. et al.Minimal change disease relapse following SARS-CoV-2 mRNA vaccine.Kidney Int. 2021; 100: 457-458Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 14Leclerc S. Royal V. Lamarche C. Laurin L.-P. Minimal change disease with severe acute kidney injury following the Oxford-AstraZeneca COVID-19 vaccine: a case report.Am J Kidney Dis. 2021; 78: 607-610Abstract Full Text Full Text PDF Scopus (39) Google Scholar, 15Komaba H. Wada T. Fukagawa M. Relapse of minimal change disease following the Pfizer-BioNTech COVID-19 vaccine.Am J Kidney Dis. 2021; 78: 469-470Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 16Maas R.J. Gianotten S. van der Meijden W.A.G. An additional case of minimal change disease following the Pfizer-BioNTech COVID-19 vaccine.Am J Kidney Dis. 2021; 78: 312Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 17Lebedev L. Sapojnikov M. Wechsler A. et al.Minimal change disease following the Pfizer-BioNTech COVID-19 vaccine.Am J Kidney Dis. 2021; 78: 142-145Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar, 18Da Y. Goh G.H. Khatri P. A case of membranous nephropathy following Pfizer–BioNTech mRNA vaccination against COVID-19.Kidney Int. 2021; 100: 938-939Abstract Full Text Full Text PDF Scopus (19) Google Scholar, 19Aydın 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 (45) Google Scholar, 20Sekar A. Campbell R. Tabbara J. Rastogi P. ANCA glomerulonephritis after the Moderna COVID-19 vaccination.Kidney Int. 2021; 100: 473-474Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar, 21Shakoor M.T. Birkenbach M.P. Lynch M. ANCA-associated vasculitis following Pfizer-BioNTech COVID-19 vaccine.Am J Kidney Dis. 2021; 78: 611-613Abstract Full Text Full Text PDF Scopus (92) Google Scholar, 22Sacker A. Kung V. Andeen N. Anti-GBM nephritis with mesangial IgA deposits after SARS-CoV-2 mRNA vaccination.Kidney Int. 2021; 100: 471-472Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 23Masset C. Kervella D. Kandel-Aznar C. et al.Relapse of IgG4-related nephritis following mRNA COVID-19 vaccine.Kidney Int. 2021; 100: 465-466Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 24Tuschen 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 (33) Google Scholar, 25Oniszczuk J. Pagot E. Limal N. et al.Scleroderma renal crisis following mRNA vaccination against SARS-CoV-2.Kidney Int. 2021; 100: 940-941Abstract Full Text Full Text PDF Scopus (9) Google Scholar). The occurrence of glomerular disease after immunization against influenza, pneumococcus, and hepatitis B has been reported in the past.26Gutierrez S. Dotto B. Petiti J.P. et al.Minimal change disease following influenza vaccination and acute renal failure: just a coincidence?.Nefrologia. 2012; 32: 414-415PubMed Google Scholar, 27Kikuchi Y. Imakiire T. Hyodo T. et al.Minimal change nephrotic syndrome, lymphadenopathy and hyperimmunoglobulinemia after immunization with a pneumococcal vaccine.Clin Nephrol. 2002; 58: 68-72Crossref PubMed Google Scholar, 28Ozdemir S. Bakkaloglu A. Oran O. Nephrotic syndrome associated with recombinant hepatitis B vaccination: a causal relationship or just a mere association?.Nephrol Dial Transplant. 1998; 13: 1888-1889Crossref PubMed Scopus (15) Google Scholar The reported patients developed acute onset nephrotic syndrome following vaccination, and kidney biopsies were consistent with a minimal change disease (MCD) pattern of injury. Although temporal association (median onset of 12 days) with vaccination and disease onset suggested a vaccine-related induction of immune injury, the pathophysiological mechanisms responsible have not been determined.Table 1Summary of reported cases of glomerular disease activation with COVID-19 vaccinationDiseaseAge, yr, median (range)% Female (n)Vaccine typeNo. of casesDe novo or flareaDe novo indicates disease development in a patient not known to have a prior glomerular disease; flare indicates activation of a known, but controlled, glomerular disease.Maintenance immune therapyTemporal association to vaccination, dTreatmentOutcomeCOVID-IgG responseReferencesIgAN38 (13–52)58 (7 of 12)Pfizer–BioNTech, Moderna125 De novo, 7 flareNo, or steroids, mycophenolic acid, calcineurin inhibitor in transplant patient1–2RASi, steroids, cyclophosphamideSpontaneous resolution, renal response to immunotherapyPositive1Hanna C. Herrera Hernandez L.P. Bu L. et al.IgA nephropathy presenting as macroscopic hematuria in 2 pediatric patients after receiving the Pfizer COVID-19 vaccine.Kidney Int. 2021; 100: 705-706Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar, 2Kudose S. Friedmann P. Albajrami O. D’Agati V.D. Histologic correlates of gross hematuria following Moderna COVID-19 vaccine in patients with IgA nephropathy.Kidney Int. 2021; 100: 468-469Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 3Anderegg M.A. Liu M. Saganas C. et al.De novo vasculitis after mRNA-1273 (Moderna) vaccination.Kidney Int. 2021; 100: 474-476Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 4Negrea L. Rovin B.H. Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathy.Kidney Int. 2021; 99: 1487Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar, 5Perrin P. Bassand X. Benotmane I. Bouvier N. Gross hematuria following SARS-CoV-2 vaccination in patients with IgA nephropathy.Kidney Int. 2021; 100: 466-468Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar, 6Tan H.Z. Tan R.Y. Choo J.C.J. et al.Is COVID-19 vaccination unmasking glomerulonephritis?.Kidney Int. 2021; 100: 469-471Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 7Rahim S.E.G. Lin J.T. Wang J.C. A case of gross hematuria and IgA nephropathy flare-up following SARS-CoV-2 vaccination.Kidney Int. 2021; 100: 238Abstract Full Text Full Text PDF PubMed Scopus (69) Google ScholarMCD61 (22–”early 80s”)36 (4 of 11)Pfizer–BioNTech, Moderna, Astra Zeneca117 De novo, 4 flareNo, or steroids, calcineurin inhibitor, rituximab1–13 (median, 7)Steroids, calcineurin inhibitorRenal response to immunotherapy in most casesPositive8Weijers J. Alvarez C. Hermans M.M.H. Post-vaccinal minimal change disease.Kidney Int. 2021; 100: 459-461Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 9Morlidge C. El-Kateb S. Jeevaratnam P. Thompson B. Relapse of minimal change disease following the AstraZeneca COVID-19 vaccine.Kidney Int. 2021; 100: 459Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar, 10D’Agati V.D. Kudose S. Bomback A.S. et al.Minimal change disease and acute kidney injury following the Pfizer-BioNTech COVID-19 vaccine.Kidney Int. 2021; 100: 461-463Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 11Schwotzer N. Kissling S. Fakhouri F. Letter regarding “Minimal change disease relapse following SARS-CoV-2 mRNA vaccine.”.Kidney Int. 2021; 100: 458-459Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 12Holzworth A. Couchot P. Cruz-Knight W. Brucculeri M. Minimal change disease following the Moderna mRNA-1273 SARS-CoV-2 vaccine.Kidney Int. 2021; 100: 463-464Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 13Kervella D. Jacquemont L. Chapelet-Debout A. et al.Minimal change disease relapse following SARS-CoV-2 mRNA vaccine.Kidney Int. 2021; 100: 457-458Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 14Leclerc S. Royal V. Lamarche C. Laurin L.-P. Minimal change disease with severe acute kidney injury following the Oxford-AstraZeneca COVID-19 vaccine: a case report.Am J Kidney Dis. 2021; 78: 607-610Abstract Full Text Full Text PDF Scopus (39) Google Scholar, 15Komaba H. Wada T. Fukagawa M. Relapse of minimal change disease following the Pfizer-BioNTech COVID-19 vaccine.Am J Kidney Dis. 2021; 78: 469-470Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 16Maas R.J. Gianotten S. van der Meijden W.A.G. An additional case of minimal change disease following the Pfizer-BioNTech COVID-19 vaccine.Am J Kidney Dis. 2021; 78: 312Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 17Lebedev L. Sapojnikov M. Wechsler A. et al.Minimal change disease following the Pfizer-BioNTech COVID-19 vaccine.Am J Kidney Dis. 2021; 78: 142-145Abstract Full Text Full Text PDF PubMed Scopus (94) Google ScholarMN68 (66–70)50 (1 of 2)Pfizer–BioNTech, Sinovac21 De novo (anti-THSD7A+), 1 flare (anti-PLA2R+)No7–14RASiNRPositive18Da Y. Goh G.H. Khatri P. A case of membranous nephropathy following Pfizer–BioNTech mRNA vaccination against COVID-19.Kidney Int. 2021; 100: 938-939Abstract Full Text Full Text PDF Scopus (19) Google Scholar,19Aydın 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 (45) Google ScholarAAN78 (52–81)33 (1 of 3)Moderna, Pfizer–BioNTech3De novoNo14Steroids, cyclophosphamide, plasma exchangeRenal responsePositive3Anderegg M.A. Liu M. Saganas C. et al.De novo vasculitis after mRNA-1273 (Moderna) vaccination.Kidney Int. 2021; 100: 474-476Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar,20Sekar A. Campbell R. Tabbara J. Rastogi P. ANCA glomerulonephritis after the Moderna COVID-19 vaccination.Kidney Int. 2021; 100: 473-474Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar,21Shakoor M.T. Birkenbach M.P. Lynch M. ANCA-associated vasculitis following Pfizer-BioNTech COVID-19 vaccine.Am J Kidney Dis. 2021; 78: 611-613Abstract Full Text Full Text PDF Scopus (92) Google ScholarAnti-GBM60 (60–”older female”)100 (2 of 2)Moderna2De novoNo1–14Steroids, cyclophosphamide, plasma exchangeNo recoveryNR6Tan H.Z. Tan R.Y. Choo J.C.J. et al.Is COVID-19 vaccination unmasking glomerulonephritis?.Kidney Int. 2021; 100: 469-471Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar,22Sacker A. Kung V. Andeen N. Anti-GBM nephritis with mesangial IgA deposits after SARS-CoV-2 mRNA vaccination.Kidney Int. 2021; 100: 471-472Abstract Full Text Full Text PDF PubMed Scopus (36) Google ScholarIgG4-RD660 (0 of 1)Pfizer–BioNTech1FlareRituximab14Steroids, rituximabRenal responsePositive23Masset C. Kervella D. Kandel-Aznar C. et al.Relapse of IgG4-related nephritis following mRNA COVID-19 vaccine.Kidney Int. 2021; 100: 465-466Abstract Full Text Full Text PDF PubMed Scopus (28) Google ScholarLN42100 (1 of 1)Pfizer–BioNTech1FlareHydroxychloroquine7Steroids, mycophenolate mofetilPartial responsePositive24Tuschen 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 (33) Google ScholarScleroderma renal crisis34100 (1 of 1)Pfizer–BioNTech1De novoNo1RASiResponsePositive25Oniszczuk J. Pagot E. Limal N. et al.Scleroderma renal crisis following mRNA vaccination against SARS-CoV-2.Kidney Int. 2021; 100: 940-941Abstract Full Text Full Text PDF Scopus (9) Google ScholarAAN, anti–neutrophil cytoplasmic antibody–associated nephritis; anti-GBM, anti–glomerular basement membrane antibody disease; COVID, coronavirus; COVID-19, coronavirus disease 2019; IgAN, IgA nephropathy; IgG4-RD, IgG4-related disease; LN, lupus nephritis; MCD, minimal change disease; MN, membranous nephropathy; NR, not reported; PLA2R, phospholipase A2 receptor; RASi, renin-angiotensin system inhibitor; THSD7a, thrombospondin type-1 domain-containing 7A.a De novo indicates disease development in a patient not known to have a prior glomerular disease; flare indicates activation of a known, but controlled, glomerular disease. Open table in a new tab AAN, anti–neutrophil cytoplasmic antibody–associated nephritis; anti-GBM, anti–glomerular basement membrane antibody disease; COVID, coronavirus; COVID-19, coronavirus disease 2019; IgAN, IgA nephropathy; IgG4-RD, IgG4-related disease; LN, lupus nephritis; MCD, minimal change disease; MN, membranous nephropathy; NR, not reported; PLA2R, phospholipase A2 receptor; RASi, renin-angiotensin system inhibitor; THSD7a, thrombospondin type-1 domain-containing 7A. After vaccination against COVID-19, reports of exacerbation, and in some cases, new onset of glomerular diseases began arriving at Kidney International and other nephrology journals. Although the development of de novo glomerular disease is intriguing, increased patient awareness of symptoms after vaccination may have prompted medical attention, revealing a previously undiagnosed kidney disease as opposed to a de novo disease. Indeed, chronicity on the kidney biopsy may suggest the glomerular disease preceded COVID-19 vaccination. Although nearly all approved vaccine platforms have been implicated, cases have been far more common after the mRNA-based vaccines, Pfizer–BioNTech BNT162b2 and Moderna mRNA1273 (Table 1). Of course, this may simply reflect more widespread use of these mRNA vaccines. Another interesting feature of COVID-19 vaccine-associated glomerular disease (CVAGD) is that most cases appear to be either IgA nephropathy (IgAN) or MCD (Table 1). The timing of IgAN activation is generally within a day or two after receiving the second dose of BNT162b2 or mRNA1273, whereas MCD appears to occur at a median of 7 days after the first dose (Table 1). Although these associations do not prove causation, we suggest that the volume of cases of MCD and IgAN and the consistent time course of events indicate a direct role of the mRNA vaccines in these 2 glomerular diseases. Several other glomerular diseases have occurred in smaller numbers following vaccination, sometimes quickly (scleroderma renal crisis), but more often after about 2 weeks (e.g., membranous nephropathy, anti–neutrophil cytoplasmic antibody–associated vasculitis, anti–glomerular basement membrane disease, and IgG4 renal disease). Given the small number of cases of these immune-mediated glomerular diseases, and the longer time to their appearance, it is difficult to be certain that they were activated by the vaccines. Nonetheless, considering these cases in aggregate, it appears that the COVID-19 vaccines can (re)activate autoantibody-mediated kidney disease. It is not clear how COVID-19 vaccines, and in particular the mRNA vaccines, induce MCD, IgAN, and other autoimmune kidney diseases. mRNA-based vaccine technology has been available for some time, although the SARS-CoV-2 vaccines were the first to be investigated in large-scale phase 3 randomized trials. It has been previously demonstrated that this vaccine technology promotes more potent immune responses than inactivated viral vaccines and even natural infection. A comparison of the immune responses to the COVID-19 vaccine platforms is given in Table 229Sahin U. Muik A. Derhovanessian E. et al.COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses.Nature. 2020; 586: 594-599Crossref PubMed Scopus (1129) Google Scholar, 30Turner J.S. O’Halloran J.A. Kalaidina E. et al.SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses.Nature. 2021; 596: 109-113Crossref PubMed Scopus (379) Google Scholar, 31Teijaro J.R. Farber D.L. COVID-19 vaccines: modes of immune activation and future challenges.Nat Rev Immunol. 2021; 21: 195-197Crossref PubMed Scopus (393) Google Scholar, 32Ewer K.J. Barrett J.R. Belij-Rammerstorfer S. et al.T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial.Nat Med. 2021; 27: 270-278Crossref PubMed Scopus (357) Google Scholar, 33Ella R. Reddy S. Jogdand H. et al.Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial.Lancet Infect Dis. 2021; 21: 950-961Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar, 34Wu Z. Hu Y. Xu M. et al.Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.Lancet Infect Dis. 2021; 21: 803-812Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar, 35Keech C. Albert G. Cho I. et al.Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine.N Engl J Med. 2020; 383: 2320-2332Crossref PubMed Scopus (755) Google Scholar. This ability of the mRNA vaccines to enhance virus-specific responses over and above more traditional vaccines has likely contributed to the high efficacy in preventing disease from SARS-CoV-2, as well as the viral variants that have evolved during this pandemic. BNT162b2 or mRNA1273 deliver lipid nanoparticle encapsulated mRNA encoding the full-length SARS-CoV-2 spike protein. These vaccines were found to be safe and efficacious in preventing severe COVID-19 in both clinical trial and real-world conditions, although patients with known autoimmune diseases were not included in the initial trials.36Thompson M.G. Burgess J.L. Naleway A.L. et al.Prevention and attenuation of Covid-19 with the BNT162b2 and mRNA-1273 vaccines.N Engl J Med. 2021; 385: 320-329Crossref PubMed Scopus (263) Google Scholar These lipid nanoparticle–mRNA vaccines stimulate robust antigen-specific T-cell responses, including T follicular helper (Tfh) cells, and potent germinal center B-cell responses, leading to durable neutralizing antibody production.37Lederer K. Castano D. Gomez Atria D. et al.SARS-CoV-2 mRNA vaccines foster potent antigen-specific germinal center responses associated with neutralizing antibody generation.Immunity. 2020; 53: 1281-1295.e1285Abstract Full Text Full Text PDF PubMed Scopus (194) Google ScholarTable 2Immune responses to SARS-CoV-2 vaccine platformsVaccineExample manufacturerT-cell responsesB-cell responsesCytokine responsesReferencesLNP-mRNAPfizer–BioNTech, ModernaAntigen-specific Th1-biased CD4+ response, CD8+ IFNɣ, IL-2Prolonged S-specific germinal center B-cell responsesIFNɣ, IL-2, type I interferon via toll-like receptor-729Sahin U. Muik A. Derhovanessian E. et al.COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses.Nature. 2020; 586: 594-599Crossref PubMed Scopus (1129) Google Scholar, 30Turner J.S. O’Halloran J.A. Kalaidina E. et al.SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses.Nature. 2021; 596: 109-113Crossref PubMed Scopus (379) Google Scholar, 31Teijaro J.R. Farber D.L. COVID-19 vaccines: modes of immune activation and future challenges.Nat Rev Immunol. 2021; 21: 195-197Crossref PubMed Scopus (393) Google ScholarAdenovirus-DNAAstraZeneca, Janssen/Johnson & JohnsonAntigen-specific Th1-biased CD4+ response, monofunctional and cytotoxic CD8+ responseIgG1/IgG3 predominant, low IgG2/IgG4IFNɣ, TNFα, IL-2, type 1 interferon via toll-like receptor-931Teijaro J.R. Farber D.L. COVID-19 vaccines: modes of immune activation and future challenges.Nat Rev Immunol. 2021; 21: 195-197Crossref PubMed Scopus (393) Google Scholar,32Ewer K.J. Barrett J.R. Belij-Rammerstorfer S. et al.T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial.Nat Med. 2021; 27: 270-278Crossref PubMed Scopus (357) Google ScholarInactivated whole virusSinovac BiotechTh1-biased response with minimal Th2RBD-specific binding antibody and neutralizing antibody productionIFNɣ, TNFα, IL-233Ella R. Reddy S. Jogdand H. et al.Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial.Lancet Infect Dis. 2021; 21: 950-961Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar,34Wu Z. Hu Y. Xu M. et al.Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.Lancet Infect Dis. 2021; 21: 803-812Abstract Full Text Full Text PDF PubMed Scopus (327) Google ScholarRecombinant protein subunitNovavaxTh1-biased response with minimal Th2S-binding antibody and neutralizing antibody productionIFNɣ, TNFα, IL-235Keech C. Albert G. Cho I. et al.Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine.N Engl J Med. 2020; 383: 2320-2332Crossref PubMed Scopus (755) Google ScholarIFNγ, interferon gamma; IL-2, interleukin 2; LNP, lipid nanoparticle; RBD, receptor-binding domain; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Th1, T-helper cell 1; Th2, T-helper cell 2; TNFα, tumor necrosis factor alpha. Open table in a new tab IFNγ, interferon gamma; IL-2, interleukin 2; LNP, lipid nanoparticle; RBD, receptor-binding domain; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Th1, T-helper cell 1; Th2, T-helper cell 2; TNFα, tumor necrosis factor alpha. In the cases of IgAN, disease symptoms occurred right after vaccination, suggesting a rapid immune mechanism, such as a memory recall response or mobilization of cells positioned to secrete galactose-deficient IgA1 antibodies. Although purely speculative, we wonder if the COVID-19 vaccines can robustly stimulate the gut-associated lymphoid tissue (Peyer patches) responsible for IgA1 production, as they do in other lymphoid tissues. IgA1 hyperresponsiveness has been observed in patients with IgAN following influenza vaccination.38van den Wall Bake A.W. Beyer W.E. Evers-Schouten J.H. et al.Humoral immune response to influenza vaccination in patients with primary immunoglobulin A nephropathy: an analysis of isotype distribution and size of the influenza-specific antibodies.J Clin Invest. 1989; 84: 1070-1075Crossref PubMed Scopus (73) Google Scholar In the case of COVID-19 vaccination, circulating IgA responses following administration have been observed to be similar in kinetics to IgG responses, with levels reaching a plateau 18 to 21 days after first mRNA dose, and further increases after a second dose peaking at 7 days after dose.39Wisnewski A.V. Campillo Luna J. Redlich C.A. Human IgG and IgA responses to COVID-19 mRNA vaccines.PLoS One. 2021; 16e0249499Crossref PubMed Scopus (103) Google Scholar The temporal associations with hematuria onset following vaccination on the order of days argues against the contribution of spike protein-specific IgA molecules from participating in disease. However, it is known that patients with IgAN have increased circulating galactose-deficient IgA1, and perhaps bystander activation of the immune system with mRNA COVID-19 vaccination may act as a trigger for the formation of immune complexes and subsequent glomerular injury. In contrast, the development of MCD following vaccination takes some time, suggesting a role for cellular immunity. Central to the pathogenesis of MCD is the development of podocyte injury due to dysregulated T-cell activation.29Sahin U. Muik A. Derhovanessian E. et al.COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses.Nature. 2020; 586: 594-599Crossref PubMed Scopus (1129) Google Scholar The COVID-19 mRNA vaccines trigger enhanced Tfh responses that peak 7 days after immunization. A potential contribution to the pathogenesis of MCD by Tfh cells has been suggested by observations that circulating subsets of Tfh cells are increased in patients with MCD, and the frequency of these populations is reduced in patients who are successfully treated with steroids.40Li T. Shi Y. Sun W. et al.Increased PD-1(+)CD154(+) Tfh cells are possibly the most important functional subset of PD-1(+) T follicular helper cells in adult patients with minimal change disease.Mol Immunol. 2018; 94: 98-106Crossref PubMed Scopus (8) Google Scholar Given these findings, and the reported onset of disease at a time point that correlates with Tfh response, perhaps mRNA vaccine-induced alterations in the Tfh population and/or their associated cytokine profile in a susceptible individual could promote podocyte injury and the development of nephrotic syndrome and MCD. The later appearing cases of autoantibody-mediated glomerular disease may be due to the induction of vaccine-associated autoimmunity. Vaccine-associated autoimmunity has been postulated to occur by antigen-specific and nonspecific mechanisms. Antigen-specific triggers for vaccine-mediated autoimmunity are thought to be secondary to molecular mimicry. That is, exposure to a non–self-antigen, such as SARS-CoV-2 spike protein, could elicit responses directed against host tissues if there was sufficient sequence homology to allow for cross-recognition. The SARS-CoV-2 spike protein shares homology with several human proteins, which may then be subject to off-target immune attack after vaccination.41Vojdani A. Vojdani E. Kharrazian D. Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: implications for autoimmune diseases.Front Immunol. 2020; 11: 617089Crossref PubMed Scopus (173) Google Scholar Consistent with the mimicry hypothesis, it has been suggested that homologous sequences between human alveolar surfactant-related proteins and SARS-CoV-2 spike glycoproteins contribute to host immune attack and the subsequent pulmonary pathology seen with COVID-19 infection.42Kanduc D. Shoenfeld Y. On the molecular determinants of the SARS-CoV-2 attack.Clin Immunol. 2020; 215: 108426Crossref PubMed Scopus (95) Google Scholar Similarly, mimicry of viral antigens with host proteins has been proposed to contribute to immune attack in the central nervous system, exacerbating neurologic complications in COVID-19.43Ellul M.A. Benjamin L. Singh B. et al.Neurological associations of COVID-19.Lancet Neurol. 2020; 19: 767-783Abstract Full Text Full Text PDF PubMed Scopus (1235) Google Scholar Antigen nonspecific mechanisms of autoimmunity with vaccination are thought to occur through bystander activation. In this model, the vaccine-stimulated immune response may trigger cellular damage and exposure of normally hidden self-antigens, which are then recognized by host immunity. Alternati" @default.
• W3200535500 created "2021-09-27" @default.
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• W3200535500 date "2021-11-01" @default.
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• W3200535500 title "COVID-19 vaccination followed by activation of glomerular diseases: does association equal causation?" @default.
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• W3200535500 doi "https://doi.org/10.1016/j.kint.2021.09.002" @default.
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