Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Buffering deleterious polymorphisms in highly constrained parts of HIV-1 envelope by flexible regions

International audienceAbstractBackgroundCovariation is an essential process that leads to coevolution of parts of proteins and genomes. In organisms subject to strong selective pressure, coevolution is central to keep the balance between the opposite requirements of antigenic variation and retention of functionality. Being the viral component most exposed to the external environment, the HIV-1 glycoprotein gp120 constitutes the main target of the immune response. Accordingly its more external portions are characterised by extensive sequence heterogeneity fostering constant antigenic variation.ResultsWe report that a single polymorphism, present at the level of the viral population in the conserved internal region C2, was sufficient to totally abolish Env functionality when introduced in an exogenous genetic context. The prominent defect of the non-functional protein is a block occurring after recognition of the co-receptor CCR5, likely due to an interference with the subsequent conformational changes that lead to membrane fusion. We also report that the presence of compensatory polymorphisms at the level of the external and hypervariable region V3 fully restored the functionality of the protein. The functional revertant presents different antigenic profiles and sensitivity to the entry inhibitor TAK 779.ConclusionsOur data suggest that variable regions, besides harbouring intrinsic extensive antigenic diversity, can also contribute to sequence diversification in more structurally constrained parts of the gp120 by buffering the deleterious effect of polymorphisms, further increasing the genetic flexibility of the protein and the antigenic repertoire of the viral population

Decay rate of antiS1/S2 IgG serum levels after 6 months of BNT162b2 vaccination in a cohort of COVID-19-naive and COVID-19-experienced subjects

Vaccination toward SARS-CoV-2 reduced mortality and ‘boosters’ are being implemented. We offer scientific contribution about IgG production in the COVID-19 experienced population. From January 2021 to March 2021, 183 residents and staff from the Elderly Nursing Home “San Giuseppe Moscati” who had received two doses of the BNT162b2 vaccine were enrolled. The antibody response was assessed by the DiaSorin LIAISON-CLIA S1/S2® IgG solution. Cutoff levels for response (>39 BAU/mL) and neutralizing activity (>208 BAU/mL) were derived from DiaSorin official data. Serology was assessed before and after the first vaccination, and 2 weeks and 6 months after the second vaccination. Anti-S IgG in COVID-19 experienced, baseline IgG producers spiked after the first vaccination to median 5044 BAU/mL and decayed at 6 months to 2467.4 BAU/mL. Anti-S IgG in COVID-19 experienced, baseline IgG non-producers spiked after the second vaccination to median 1701.7 BAU/mL and decayed at 6 months to 904.8 BAU/mL. Anti-S IgG in COVID-19 naïve subjects spiked after the second vaccination to median 546 BAU/mL and decayed at 6 months to 319.8 BAU/mL. The differences between sequential timepoint levels in each group were statistically significant (p < .0001). Serology analysis revealed different kinetics between COVID-19 experienced subjects depending on baseline response, possibly predicting different IgG persistence in blood