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      Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathy

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      Kidney International
      Elsevier BV

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          Abstract

          To the Editor: Several of the SARS-CoV2 vaccines use a nucleoside-modified, purified mRNA lipid nanoparticle-encapsulated platform. Compared to traditional inactivated viral and adjuvanted protein vaccines, this RNA platform elicits far higher neutralizing antibody titers, stronger antigen-specific CD4+ and CD8+ T cells responses, and stronger germinal center B and TFH cell activation in experimental animals 1 . The activated CD4+ and CD8+ T cells produce several proinflammatory cytokines, including interferon-γ and tumor necrosis factor-α. This led us to wonder if these vaccines may activate or exacerbate immune-mediated glomerular diseases. Two individuals with biopsy-proven IgA nephropathy (IgAN) developed gross hematuria shortly following the second dose of the Moderna vaccine. The patients are described in the Table . At baseline, both had proteinuria below 1 gram/day and well-preserved kidney function. Several hours after the second dose of vaccine was given, both developed systemic symptoms ranging from body aches, headache, and fatigue to fever and chills. Between 8 and 24 hours after systemic symptoms appeared, the patients noticed gross hematuria that resolved after 3 days. Serum creatinine did not increase, but proteinuria increased in one patient (Table). Although we did not expect an exacerbation of IgAN after a non-mucosal immune challenge, IgAN patients have previously been reported to have a stronger IgA1 (albeit monomeric) response to intramuscular influenza vaccine than healthy subjects 2 . These episodes of apparent IgAN exacerbation should prompt the nephrology community to closely follow their patients with glomerular disease post SAR2-CoV2 vaccination to determine the frequency and consequences of vaccine-induced disease activation. Table 1 Patient Demographics and Clinical Characteristics Patient Age Sex Race Year IgAN diagnosed Treatment Gross hematuria events during disease course Persistent microscopichematuria ProteinuriaIn 2020 Proteinuria between SARS-Cov2 vaccine doses Proteinuria 3 weeks after last SARS-CoV2 vaccine dose 1 38 F 1 W 2005 RAASi At presentation;During one episode of gastroenteritis;Occasionally after yearly influenzavaccine Yes 0.63 g/d 0.82 g/d 1.40 g/d 2 38 F W 2019 Cyc+Pred (6 months) then RAASi At presentation only Yes 0.43 g/d 0.59 g/d 0.40 g/d 1Abbreviations: F, female; W, white; RAASi, renin-angiotensin-aldosterone system inhibitor; Cyc, cyclophosphamide; Pred, prednisone; g/d, grams/day

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          Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses

          Pardi and colleagues report on a vaccine platform in which purified, antigen-encoding, nucleoside-modified mRNA is encapsulated in lipid nanoparticles. Immunization with this vaccine elicits potent T follicular helper cell, germinal center B cell, and protective, neutralizing antibody responses.
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            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.

            Primary IgA nephropathy (IgAN) is characterized by mesangial deposits of IgA1, increased serum IgA1 levels, and circulating immune complexes containing predominantly IgA1. It has previously been found that patients with IgAN have a higher than normal IgA response to vaccination, but the IgA subclasses have not been studied. To investigate whether the IgA hyperresponsiveness is limited to the subclass IgA1, which is involved in the pathogenesis of IgAN, we compared the immune responses of 18 patients with 22 healthy controls after intramuscular vaccination with inactivated influenza virus. Antibody titers were significantly higher (P less than 0.0001) for the IgA1 subclass in patients versus controls, but not for the other isotypes. A substantial portion of the IgA and IgA1 antiinfluenza immune response comprised polymers in both patients and controls. There was no preferential response of polymers in patients. Patients produced significantly more monomeric IgA1 antibodies than controls. These results show that patients with IgAN have a hyperresponsiveness limited to the subclass IgA1 and mainly expressed by an excess of monomers.
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              Author and article information

              Contributors
              (View ORCID Profile)
              Journal
              Kidney International
              Kidney International
              Elsevier BV
              00852538
              June 2021
              June 2021
              : 99
              : 6
              : 1487
              Article
              10.1016/j.kint.2021.03.002
              b2fb1514-eb09-41d2-ac84-a5b45010403d
              © 2021

              https://www.elsevier.com/tdm/userlicense/1.0/

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