IgA nephropathy presenting as macroscopic hematuria in 2 pediatric patients after receiving the Pfizer COVID-19 vaccine.
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ABSTRACT:
SUBMITTER: Hanna C
PROVIDER: S-EPMC8256683 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC8942577 | biostudies-literature
Project description:IgA nephropathy (IgAN), characterized by mesangial IgA1 deposits, is a leading cause of renal failure worldwide. IgAN pathogenesis involves circulating hypogalactosylated IgA1 complexed with soluble IgA Fc receptor I (sCD89) and/or anti-hypogalactosylated-IgA1 autoantibodies, but no specific treatment is available for IgAN. The absence of IgA1 and CD89 homologs in the mouse has precluded in vivo proof-of-concept studies of specific therapies targeting IgA1. However, the ?1KI?CD89Tg mouse model of IgAN, which expresses human IgA1 and human CD89, allows in vivo testing of recombinant IgA1 protease (IgA1?P), a bacterial protein that selectively cleaves human IgA1. Mice injected with IgA1?P (1-10 mg/kg) had Fc fragments of IgA1 in both serum and urine, associated with a decrease in IgA1-sCD89 complexes. Levels of mesangial IgA1 deposits and the binding partners of these deposits (sCD89, transferrin receptor, and transglutaminase 2) decreased markedly 1 week after treatment, as did the levels of C3 deposition, CD11b(+) infiltrating cells, and fibronectin. Antiprotease antibodies did not significantly alter IgA1?P activity. Moreover, hematuria consistently decreased after treatment. In conclusion, IgA1?P strongly diminishes human IgA1 mesangial deposits and reduces inflammation, fibrosis, and hematuria in a mouse IgAN model, and therefore may be a plausible treatment for patients with IgAN.
| S-EPMC5004657 | biostudies-literature
Project description:Enhanced intrarenal renin-angiotensin system (RAS) is implicated in the development and progression of renal injury. To investigate whether angiotensinogen (AGT) expression is involved in glomerular RAS activity and glomerular injury, we examined glomerular AGT expression and its correlation with expression of other RAS components, and levels of glomerular injury in samples from patients with immunoglobulin A nephropathy (IgAN) (23) and minor glomerular abnormalities (MGA) (8). Immunohistochemistry showed that AGT protein was highly expressed by glomerular endothelial cells (GEC) and mesangial cells in nephritic glomeruli of IgAN compared with glomeruli of MGA. Levels of glomerular AGT protein were well correlated with levels of glomerular angiotensin II (ang II), transforming growth factor-beta (TGF-beta), alpha-smooth-muscle actin, glomerular cell number, and glomerulosclerosis score but not with those of glomerular angiotensin-converting enzyme and ang II type 1 receptor. Real-time polymerase chain reaction (RT-PCR) and Western blot analyses using cultured human GEC indicated that ang II upregulated AGT messenger ribonucleic acid (mRNA) and protein expression in a dose- and time-dependent manner. These data suggest that activated glomerular AGT expression is likely involved in elevated local ang II production and, thereby, may contribute to increased TGF-beta production and development of glomerular injury in IgAN. Augmentation of GEC-AGT production with ang II stimulation might drive further glomerular injury in a positive-feedback loop.
| S-EPMC2441593 | biostudies-other
Project description:Introduction Miller Fisher syndrome (MFS) is a rare variant of Guillain-Barre syndrome characterized by ataxia, areflexia, and ophthalmoplegia. We present a case of MFS following Pfizer COVID-19 vaccine. Case presentation A previously healthy 24-year-old female presented with binocular horizontal diplopia 18 days after receiving the first dose of Pfizer COVID-19 vaccine (Comirnaty®). Anti-ganglioside testing revealed positive anti-GQ1b antibodies. Intravenous immunoglobulins were administered, in a dose of 2 g per kg of body weight over 5 days. On a follow-up exam 3 weeks after the treatment, clinical improvement was noted with normal bulbomotor examination. Conclusion Patients with acute ophthalmoplegia occurring after COVID-19 vaccination should be screened for the presence of anti-GQ1b antibody. If the antibody is present, intravenous immunoglobulin should be administered as it may hasten clinical improvement. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05776-0.
| S-EPMC8611397 | biostudies-literature
Project description:The hallmark of IgA nephropathy (IgAN) is gross hematuria (GH) coinciding with or immediately following an upper respiratory or gastrointestinal tract infection and can represent the disease triggering event. Therefore, a whole genomic screening of IgAN patients during the GH was done to clarify the link between mucosal encountered antigens and the occurrence of glomerular hematuria. The modulated genes during GH show a clear involvement of the interferon signalling, antigen presenting pathway, and the immuno-proteasome. The gene characterizing cytotoxic effector lymphocytes (CX3CR1) implicated in vascular endothelial damage, was found up-regulated at both mRNA and protein level. In vitro antigenic stimulation of PBMCs on an independent set of IgAN patients and healthy blood donors (HBS) demonstrated that patients upregulate specifically CX3CR1 in an enhanced and dose dependant manner, while an expected down-regulation occurred in HBD. This enhanced activation occurred in both patients characterized by recurrent GH and by permanent microscopic hematuria (MH). We then analyzed glomerular fractalkine (FKN) expression, since this ligand is involved in the vascular gateway for CX3CR1+ cells towards the inflamed tissues. A significantly higher FKN expression on the capillary vessels and podocytes was found in recurrent GH patients compared to permanent MH, suggesting a predisposition for cytotoxic cell extravasation in recurrent GH patients. Taken together, our findings demonstrate, for the first time, a defect in antigen handling in PBMCs of IgAN patients with a specific up-regulation of CX3CR1. Furthermore, the constitutive up regulation of glomerular FKN, suggests an involvement of the CX3CR1-FKN axis in the exacerbation of GH.
2012-03-30 | GSE27676 | GEO
Project description:Immunoglobulin A nephropathy (IgAN) is a major cause of secondary hypertension (HT) of renal origin - a significant prognostic factor of IgAN. In children, similar to HT, prehypertension (pre-HT) is becoming a significant health issue. However, the role of secondary HT and pre-HT (HT/pre-HT) in the progression of pediatric IgAN remains unclear. We investigated the effects of HT/pre-HT on prognosis and its determinants as well as their correlation with clinicopathological parameters to identify more effective therapeutic targets.This single-center retrospective study compared clinicopathological features and treatment outcomes between patients with and without HT/pre-HT in 108 children with IgAN. Independent risk factors for HT/pre-HT were evaluated; segmental glomerulosclerosis was a significant variable, whose relationship with clinicopathological parameters was analyzed.Clinical outcomes of patients with and without HT/pre-HT differed considerably (P = .006) on ≥6 months follow-up. Patients with HT/pre-HT reached complete remission less frequently than those without HT/pre-HT (P = .014). Age, serum creatinine, prothrombin time, and segmental glomerulosclerosis or adhesion were independent risk factors for HT/pre-HT in pediatric IgAN (P = .012, P = .017, P = .002, and P = .016, respectively). Segmental glomerulosclerosis or adhesion was most closely associated with glomerular crescents (r = 0.456, P < .01), followed by Lees grades (r = 0.454, P < .01), renal arteriolar wall thickening (r = 0.337, P < .01), and endocapillary hypercellularity (r = 0.306, P = .001). The intensity of IgA deposits, an important marker of pathogenetic activity in IgAN, was significantly associated with the intensity and location of fibrinogen deposits (intensity: r = 0.291, P = .002; location: r = 0.275, P = .004).HT/pre-HT in pediatric IgAN patients is an important modifiable factor. A relationship is observed between HT/pre-HT and its determinants, especially segmental glomerulosclerosis. Potential therapeutic approaches for IgAN with HT/pre-HT might be directed toward the management of coagulation status, active lesions, and hemodynamics for slowing disease progression.
| S-EPMC7535649 | biostudies-literature
Project description:The hallmark of IgA nephropathy (IgAN) is gross hematuria (GH) coinciding with or immediately following an upper respiratory or gastrointestinal tract infection and can represent the disease triggering event. Therefore, a whole genomic screening of IgAN patients during the GH was done to clarify the link between mucosal encountered antigens and the occurrence of glomerular hematuria. The modulated genes during GH show a clear involvement of the interferon signalling, antigen presenting pathway, and the immuno-proteasome. The gene characterizing cytotoxic effector lymphocytes (CX3CR1) implicated in vascular endothelial damage, was found up-regulated at both mRNA and protein level. In vitro antigenic stimulation of PBMCs on an independent set of IgAN patients and healthy blood donors (HBS) demonstrated that patients upregulate specifically CX3CR1 in an enhanced and dose dependant manner, while an expected down-regulation occurred in HBD. This enhanced activation occurred in both patients characterized by recurrent GH and by permanent microscopic hematuria (MH). We then analyzed glomerular fractalkine (FKN) expression, since this ligand is involved in the vascular gateway for CX3CR1+ cells towards the inflamed tissues. A significantly higher FKN expression on the capillary vessels and podocytes was found in recurrent GH patients compared to permanent MH, suggesting a predisposition for cytotoxic cell extravasation in recurrent GH patients. Taken together, our findings demonstrate, for the first time, a defect in antigen handling in PBMCs of IgAN patients with a specific up-regulation of CX3CR1. Furthermore, the constitutive up regulation of glomerular FKN, suggests an involvement of the CX3CR1-FKN axis in the exacerbation of GH. Gene expression profile comparison 3 IgAN patients at two different clinical time points, the first sample during the gross hematuria episode and the second during the remission phase of the disease characterized by microscopic hematuria
2012-03-29 | E-GEOD-27676 | biostudies-arrayexpress
Project description: Not available
| S-DIXA-D-1084 | biostudies-other
Project description:On May 10, 2021, the Emergency Use Authorization of the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) was expanded to include adolescents (May 10, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use). We describe clinical characteristics of 8 adolescents who presented over the course of 36 days to Nicklaus Children's Hospital with perimyocarditis within 4 days of receiving a dose of BNT162b2 vaccine.
| S-EPMC8344528 | biostudies-literature
Project description:Hereditary C2 deficiency is the most common early complement deficiency and characterized by recurrent infections and autoimmunity despite most patients are also asymptomatic. Type I hereditary C2 deficiency is caused by a heterozygous deletion in C2 gene resulting in early stop codon and lack of C2 production. Clinical spectrum may vary and pure nephrological involvement without the presence of recurrent infections is scarce in hereditary C2 deficiency.We report here a previously healthy 14-year-old boy presenting recurrent self-limited macroscopic hematuria and persistently low serum C4 levels, diagnosed as having type I hereditary C2 deficiency with confirming a novel heterozygote deletion (c.1567?+?22_1567?+?43del) in C2 gene. He has been remained asymptomatic for the next 18 months. Since the diagnosis of C2 deficiency was made in the absence of organ-threatening involvement such as immune complex-mediated glomerulonephritis, we think that early diagnosis and optimal follow-up may improve life-span of the patients with hereditary early complement deficiencies.
| S-EPMC7502104 | biostudies-literature