Clinico-pathological considerations in a 48-years-old female with acute kidney injury: is it lupus nephritis, ANCA-associated vasculitis or something else?

BACKGROUND: The value of ANCA positivity in the setting of systemic lupus erythematous and their pathogenicity remains uncertain. CASE PRESENTATION: We report the case of a 48-year-old female with rapidly progressive kidney failure, arthro-myalgia and weight loss. Auto-immune screening showed anti-dsDNA antibodies, complement consumption and triple ANCA positivity. A first kidney biopsy done at presentation highlighted class IV-G glomerulonephritis with elective extra-capillary involvement and mainly C1q glomerular deposition at immunofluorescence study. After three months of a regimen combining steroids and cyclophosphamide, a second biopsy was performed and showed class IV-G glomerulonephritis with mainly endocapillary proliferation. CONCLUSION: This case is atypical in view of immunological profile and kidney histopathological presentation and evolution and gives rise to discussion in view of recent data on ANCA value in lupus nephritis, and suggests that different auto-immune pathways may be involved in lupus nephritis

Early post-transplant serum IgA level is associated with IgA nephropathy recurrence after kidney transplantation

IgA nephropathy (IgAN), the most frequent primary glomerulonephritis, affects young patients and is associated with a high risk of progression to end-stage renal disease. Consequently, patients with IgAN constitute an important proportion of candidates for kidney transplantation. Several studies showed a significant risk of IgAN recurrence on kidney graft, but the risks factors for recurrence remain to be accurately evaluated. Indeed, early identification of at risk patients may allow the optimization of treatment and the reduction of recurrence rate on the graft. In the present work, we studied the relationship between post-transplant serum IgA (sIgA) levels and the risk of IgAN recurrence after kidney transplantation. Recipients with IgAN had higher levels of sIgA as compared to patients with other nephropathies (p<0.05). The prevalence of IgAN recurrence was 20.8% during the period of analysis (mean follow-up of 6 ± 3.2 years). Serum IgA levels at M6, M12 and M24 post-transplant were significantly higher in patients with IgAN recurrence as compared to those without (p = 0.009, p = 0.035 and p = 0.029, respectively). Using receiver operating curve (ROC), sIgA at M6 and M12 post-transplant were significantly associated with IgAN recurrence (AUC = 0.771, p = 0.004 and AUC = 0.767, p = 0.016, respectively), while serum creatinine and proteinuria were not. Serum IgA level at month 6 was significantly associated with the occurrence of post-transplant IgA recurrence, whether it was analyzed as a continuous or a categorical variable. After successive adjustment on age, gender and proteinuria, sIgA remained a significant risk factor of post-transplant IgAN recurrence. Finally, survival free of IgAN recurrence was significantly better in patients with sIgA<222 mg/dL at month 6 as compare to IgAN patients with sIgA≥222 mg/dL (p = 0.03). Thus, the present work supports a link between post-transplant sIgA levels and IgAN recurrence and suggests that sIgA may be a valuable predictive biomarker of IgAN recurrence in kidney transplant recipients

Novel chimeric proteins mimicking SARS-CoV-2 spike epitopes with broad inhibitory activity

SARS-CoV-2 spike (S) protein mediates virus attachment to the cells and fusion between viral and cell membranes. Membrane fusion is driven by mutual interaction between the highly conserved heptad-repeat regions 1 and 2 (HR1 and HR2) of the S2 subunit of the spike. For this reason, these S2 regions are interesting therapeutic targets for COVID-19. Although HR1 and HR2 have been described as transiently exposed during the fusion process, no significant antibody responses against these S2 regions have been reported. Here we designed chimeric proteins that imitate highly stable HR1 helical trimers and strongly bind to HR2. The proteins have broad inhibitory activity against WT B.1 and BA.1 viruses. Sera from COVID-19 convalescent donors showed significant levels of reactive antibodies (IgG and IgA) against the HR1 mimetic proteins, whereas these antibody responses were absent in sera from uninfected donors. Moreover, both inhibitory activity and antigenicity of the proteins correlate positively with their structural stability but not with the number of amino acid changes in their HR1 sequences, indicating a conformational and conserved nature of the involved epitopes. Our results reveal previously undetected spike epitopes that may guide the design of new robust COVID-19 vaccines and therapies.This work was supported by grants CV20.26565 from the Consejería de Economía y Conocimiento, Junta de Andalucía (Spain), PID2019.107515RB.C21 from the Spanish State Research Agency (SRA/10.13039/501100011033), and co-funded by ERDF/ESF, “A way to make Europe”/“Investing in your future”. The work performed in C.M.'s laboratory was supported by grants from ANRS (Agence Nationale de Recherches sur le SIDA et les hépatites virales), the Investissements d'Avenir program managed by the ANR under reference ANR-10-LABX-77 and EHVA (No. 681032, Horizon 2020). Work in S.B.'s laboratory was supported by grants from the Agence Nationale de la Recherche (ANR) (ANR-11-LABX-0070_TRANSPLANTEX), the INSERM (UMR_S 1109), the Institut Universitaire de France (IUF), all the University of Strasbourg (IDEX UNISTRA), the European Regional Development Fund (European Union) INTERREG V program (project no. 3.2 TRIDIAG) and MSD-Avenir grant AUTOGEN. We are grateful to the Spanish Radiation Synchrotron Source (ALBA), Barcelona, Spain and the European Synchrotron Radiation Facility (ESRF), Grenoble, France, for the provision of time and staff assistance at XALOC (ALBA) and ID30B and ID23-2 (ESRF) beamlines during diffraction data collection. We thank María Carmen Salinas-García for her assistance in carrying out the crystallization screenings. We also thank Pilar González-García for helping us with the statistical analysis

Hypogammaglobulinemia and risk of severe infection in kidney transplant recipients

Background Recent data have outlined a link between hypogammaglobulinemia (HGG) and infection risk and suggested that HGG correction may decrease post‐transplant infections. Methods We analyzed the risk factors of HGG and the relationship between HGG and the risk of severe infection in a cohort of 318 kidney transplant recipients (KTR) who were transplanted between 2003 and 2013. Immunoglobulin (Ig) concentration was measured prospectively at day 15 (D15), month 6 (M6), month 12 (M12), and month 24 (M24) post transplant. Results The prevalence of IgG HGG was 56% and 36.8% at D15 and M6, respectively. Age was the sole identified risk factors for D15 IgG HGG (odds ratio [OR] 1.02, P = 0.019). Risk factors for M6 IgG HGG were the presence of D15 IgG HGG (OR 6.41, P < 0.001) and treatment of acute rejection (OR 2.63, P = 0.014). Most infections occurred between D15 and M6 post transplant. Only age (hazard ratio 1.03, P < 0.001) was identified as a risk factor of infection between D15 and M6 post transplant. Survival free of infection (overall infections and bacterial or viral infections) did not differ significantly between patients with or without D15 IgG HGG. Only septicemia occurring between M6 and M12 post transplant was more frequently observed in patients with HGG. The low prevalence of severe HGG (<400 mg/dL) did not allow conclusions on the infectious risk associated with this patient subgroup. Conclusions This study does not support the existence of a strong link between post‐transplant HGG and the risk of severe infections in KTR. Correction of HGG to minimize the risk of severe infections in KTR is thus questionable and needs to be reevaluated in prospective studies