The immunogenicity of a two-dose mRNA COVID-19 vaccine regimen is low in kidney transplant (KT) recipients. Here, we provide a thorough assessment of the immunogenicity of a three-dose COVID-19 vaccine regimen in this population. We performed a prospective longitudinal study in sixty-one KT recipients given three doses of the BNT162b2 COVID-19 vaccine. We performed semi-structured pharmacovigilance interviews and monitored donor-specific antibodies and kidney function. We compared levels of anti-spike IgG, pseudo-neutralization activity against vaccine homologous and heterologous variants, frequency of spike-specific interferon (IFN)-γ-secreting cells, and antigen-induced cytokine production 28 days after the second and third doses. Reactions to vaccine were mild. One patient developed donor-specific anti-HLA antibodies after the second dose which could be explained by non-adherence to immunosuppressive therapy. Spike-specific IgG seroconversion raised from 44·3% (n=27) after the second dose to 62·3% (n=38) after the third dose (p<0·05). The mean level of spike-specific IgG increased from 1620 (SD, 3460) to 8772 (SD, 16733) AU/ml (p<0·0001). Serum neutralizing activity increased after the third dose for all variants of concern tested including the Delta variant (p<0·0001). The frequency of spike-specific IFN-γ-secreting cells increased from 19·9 (SD, 56·0) to 64·0 (SD, 76·8) cells/million PBMCs after the third dose (p<0·0001). A significant increase in IFN-γ responses was also observed in patients who remained seronegative after three doses (p<0·0001). A third dose of the BNT162b2 vaccine increases both cross-variant neutralizing antibody and cellular responses in KT recipients with an acceptable tolerability profile. Nice University Hospital, University Cote d'Azur.

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Background and objectives: Membranous nephropathy is a rare autoimmune kidney disease whose increasing prevalence in industrialized countries pleads for the involvement of an environmental factor in the development of the disease. In addition, the predominance of men in membranous nephropathy, classically attributed to biologic or genetic differences between men and women, could also be due to different occupational exposures. To support this hypothesis, we sought to describe the toxic occupational exposures of patients with membranous nephropathy. Design, setting, participants, & measurements: In this observational epidemiologic study, we compared the occupations and toxic occupational exposures of 100 patients with membranous nephropathy with those of the general population, consisting of two cohorts of 26,734,000 and 26,500 French workers. We then compared the characteristics of patients exposed to an occupational toxic substance with those of unexposed patients. Results: Patients with membranous nephropathy worked more frequently in the construction sector than the general population (33% versus 7%, P<0.001). This difference remained significant by age and sex. They were also more frequently exposed to toxic substances, such as asbestos (16% versus 5%, P<0.001), lead (9% versus 1%, P<0.001), or organic solvents (37% versus 15%, P<0.001), than the general population. The predominance of men in the subgroup of patients occupationally exposed to toxic substances was not observed in unexposed individuals (organic solvents: 80% men versus 41%, P<0.001; asbestos: 90% men versus 55%, P=0.004). In addition, patients with phospholipase A2 receptor 1 (PLA2R1) epitope spreading were more frequently exposed to asbestos and organic solvents than patients without epitope spreading (32% versus 7%, P=0.02 and 74% versus 43%, P=0.02, respectively), with a dose-dependent effect. Conclusions: Patients with membranous nephropathy were more frequently exposed to certain occupational toxic substances, such as asbestos and organic solvents, than the general population. This occupational exposure was more frequent in men and in patients with PLA2R1 epitope spreading. Clinical Trial registry name and registration number: Immunopathological Analysis in a French National Cohort of Membranous Nephropathy (IHMN), NCT04326218. Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_10_25_CJN02930322.mp3.

While air pollution is a major issue due to its harmful effects on human health, few studies focus on its impact on the immune system and vulnerability to viral infections. The lockdown declared following the COVID-19 pandemic represents a unique opportunity to study the large-scale impact of variations in air pollutants in real life. We hypothesized that variations in air pollutants modify Th1 response represented by interferon (IFN) γ production. We conducted a single center paired pilot cohort study of 58 participants, and a confirmation cohort of 320 participants in Nice (France), with for each cohort two samplings at six months intervals. We correlated the variations in the production of IFNγ after non-specific stimulation of participants’ immune cells with variations in key regulated pollutants: NO₂, O₃, PM_2.5, and PM₁₀ and climate variables. Using linear regression, we studied the effects of variations of each pollutant on the immune response. In the pilot cohort, IFNγ production significantly decreased by 25.7% post-lockdown compared to during lockdown, while NO₂ increased significantly by 46.0%. After the adjustment for climate variations during the study period (sunshine and temperature), we observed a significant effect of NO₂ variation on IFNγ production (P=0.03). In the confirmation cohort IFNγ decreased significantly by 47.8% and after adjustment for environmental factors and intrinsic characteristics we observed a significant effect of environmental factors: NO₂, PM₁₀, O₃, climatic conditions (sunshine exposure, relative humidity) on variation in IFNγ production (P=0.005, P<0.001, P=0.001, P=0.002 and P<0.001 respectively) but not independently from the BMI at inclusion and the workplace P=0.007 and P<0.001 respectively). We show a weakening of the antiviral cellular response in correlation with an increase of pollutants exposition. Agence Nationale de la Recherche, Conseil Départemental des Alpes-Maritimes and Region Sud.

Membranous nephropathy can lead to end-stage kidney disease, for which kidney transplantation is the preferred therapy. However, the disease often relapses, which can impact allograft survival. We conducted a prospective multicenter study in France involving 72 patients with membranous nephropathy who were awaiting and then underwent kidney transplantation. In addition, we established a retrospective validation cohort of 65 patients. The primary objective was to evaluate the prognostic significance of pretransplant anti phospholipase A2 receptor 1 (PLA2R1) antibodies on the recurrence of membranous nephropathy. The study also assessed the incidence rate, time to onset, and risk factors for recurrence, as well as allograft outcome. The prospective cohort showed a 26% cumulative incidence of membranous nephropathy recurrence after a median follow-up of 23.5 months. This was confirmed by a 28% cumulative incidence after a median follow-up of 67 months in the retrospective cohort. A strong association was found between the presence of anti-PLA2R1 antibodies prior to transplantation and the risk of disease recurrence (risk ratio = 5.9; 95% confidence interval [CI]: 2.3–15.7; P < 0.0001). These results were confirmed in the retrospective cohort. Monitoring of anti-PLA2R1 antibodies in the immediate posttransplant period is of limited value, because recurrence occurred early in the first 6 months (median delay of 5 [3–14] months) after transplantation despite decreasing antibody levels. The presence of anti-PLA2R1 antibodies prior to transplantation was a strong predictor of recurrence of allograft membranous nephropathy. An individualized immunomonitoring and management strategy for kidney transplant candidates with anti-PLA2R1-associated membranous nephropathy should be considered.