HLA Does Not Impact on Short-Medium-Term Antibody Response to Preventive Anti-SARS-Cov-2 Vaccine.

The response to anti-SARS-Cov-2 preventive vaccine shows high interpersonal variability at short and medium term. One of the explanations might be the individual HLA allelic variants. Indeed, B cell response is stimulated and sustained by CD4+ T helper cells activated by antigens presented by HLA-class II alleles on antigen-presenting cells (APCs). The impact of the number of antigens binding to HLA class-II alleles on the antibody response to the COVID vaccine has been assessed in a cohort of 56 healthcare workers who received the full schedule of the Pfizer-BioNTech BNT162b2 vaccine. Such vaccine is based on the entire spike protein of the SARS-CoV-2. Ab titers have been evaluated 2 weeks after the first dose as well as 2 weeks and 4 months after the boosting dose. HLA-DRB1 and DBQ1 for each of the vaccinees have been assessed, and strong binders have been predicted. The analysis showed no significant correlation between the short-medium-term Ab titers and the number of strong binders (SB) for each individual. These results indicate that levels of Ab response to the spike glycoprotein is not dependent on HLA class II allele, suggesting an equivalent efficacy at global level of the currently used vaccines. Furthermore, the pattern of persistence in Ab titer does not correlate with specific alleles or with the number of SBs.

Mixed hemodiafiltration reduces erythropoiesis stimulating agents requirement in dialysis patients: a prospective randomized study.

BACKGROUND: Improved responsiveness to erythropoiesis stimulating agents (ESAs) in patients on on-line post-dilution hemodiafiltration (Post-HDF) compared with conventional hemodialysis (HD) was reported by some authors but challenged by others. This prospective, cross-over randomized study tested the hypothesis that an alternative infusion modality of HDF, mixed-dilution HDF (Mixed HDF), could further reduce ESAs requirement in dialysis patients compared to the traditional Post-HDF. METHODS: One-hundred-twenty prevalent patients from 6 Dialysis Centers were randomly assigned to two six-months treatment sequences: A-B and B-A (A, Mixed HDF; B, Post-HDF). Primary outcome was comparative evaluation of ESA (darbepoetin alfa) requirement and ESA resistance. Treatments efficiency, iron and vitamins status, inflammation and nutrition parameters were monitored. RESULTS: In sequence A, darbepoetin requirement decreased during Mixed HDF from 29.5 to 23.7 µg/month and increased significantly during Post-HDF (32.3 µg/month at 6th month) while, in sequence B, it increased during Post-HDF from 38.2 to 43.7 µg/month and decreased during Mixed HDF (23.9 µg/month at 6th month). Overall, EPO doses at 6 months on Mixed and Post-HDF were 23.8 and 38.4 µg/month, respectively, P < 0.01. A multiple linear model confirmed that Mixed HDF vs Post-HDF reduced significantly ESA requirement and ESA resistance (P < 0.0001), by a mean of 29% (CI 23-35%) in the last three months of the observation periods. CONCLUSIONS: Mixed HDF decreased darbepoetin-alfa requirement in dialysis patients. This might help preventing the untoward side effects of high ESA doses, besides having a remarkable economic impact. Additional evidence is needed to confirm this potential benefit of Mixed-HDF.

Expression profile of HLA-B*38:55Q allele.

The identification of null or questionably expressed HLA allelic variants is a major issue in HLA diagnostics, because the mistyping of the aberrant expression of such alleles can have a major impact on the outcome of both hematopoietic stem cell transplantation (HSCT) and solid organ transplants. It is debated how questionable (Q) alleles, because of their unknown expression profile, should be considered in an allogenic HSCT setting. The HLA-B*38:55Q allele was detected as an HLA-B blank specificity; DNA sequencing identified a single polymorphism at position 373 in exon 3 (TGC > CGC), which results in the replacement of cysteine 101 with an arginine in the HLA-B heavy chain, thus, impairing disulfide bridge formation in the alpha-2 domain, essential for the normal expression of the HLA molecules. In order to determine the RNA and protein expression profile of this allelic variant, we analyzed antigenic expression at different levels, transcriptional and transductional, using a combination of cellular methods, such as serological testing and flow cytometric analysis, polymerase chain reaction (PCR) sequence-specific primer (SSP) cDNA group-specific amplification and immunocytochemical assay, demonstrating the prevalent cytoplasmatic distribution of the HLA-B*38:55Q protein. Our findings suggest that in matching process the HLA-B*38:55Q allele needs to be considered as a low expressed allele, able to elicit an allogenic T-cell response in vivo and impair the transplant outcome.

An algorithm for predicting blood loss and transfusion risk after total hip arthroplasty.

INTRODUCTION: Patients receiving blood transfusions after total hip arthroplasty have increased morbidity and longer lengths of stay compared to non-transfused patients. The aim of this study is to create an algorithm in order to identify patients at risk for transfusion after total hip replacement and define a safe point in hemoglobin levels after which the need for blood, transfusion can be excluded. METHODS: This retrospective study analyzed hemoglobin (Hb) levels for 5 days in patients undergoing total hip replacement. An algorithm was implemented to identify the critical trends of Hb levels in the first two postoperative days, trying to identify the patients at high risk of transfusion. Specificity, sensibility and efficiency were calculated in relation to the capability of the algorithm to correctly identify transfused patients. RESULTS: The algorithm found a pre-operative Hb ≥ 13 g/dl as a cut off between patients at low-risk or high-risk for transfusion. When parameters were calculated considering the best efficiency with the least number of false negatives, the algorithm showed a specificity of 84% and a sensitivity of 70% with an efficiency of 80.6%. Hb values >10 g/dl in the first operative day for low-risk patients and Hb level > 11 g/dl the second post-operative day for high-risk patients led to exclusion of the need for transfusion. CONCLUSIONS: The algorithm suggested critical Hb levels to predict transfusion. In association with clinical data, the suggested critical values of Hb may be useful to schedule lab tests and a safe early discharge.

Long-term effects of high-efficiency on-line haemodiafiltration on uraemic toxicity. A multicentre prospective randomized study.

BACKGROUND: Haemodiafiltration (HDF) may improve survival of chronic dialysis patients. This prospective, multicentre randomized cross-over study evaluated the effects of long-term on-line HDF on the levels of solutes of different molecular weight markers or causative agents of the most common metabolic derangements in uraemia. METHODS: Sixty-nine patients from eight Italian centres were randomly assigned to two 6-month treatment sequences: A-B and B-A [A, low-flux haemodialysis (HD) and B, on-line HDF]. Comparative evaluation of basal levels of small, medium-sized and protein-bound solutes at the end of the two treatment periods and analysis of parameters dependence during the interventions were performed. RESULTS: On-line HDF showed greater efficiency than low-flux HD in removing small solutes (eKt/Vurea 1.60 ± 0.31 versus 1.44 ± 0.26, P < 0.0001) and in reducing basal levels of beta2-microglobulin (22.2 ± 7.8 versus 33.5 ± 11.8 mg/L, P < 0.0001), total homocysteine (15.4 ± 5.0 versus 18.7 ± 8.2 µmol/L, P = 0 .003), phosphate (4.6 ± 1.3 versus 5.0 ± 1.4 mg/dL, P = 0.008) and, remarkably, of intact parathyroid hormone (202 ± 154 versus 228 ± 176 pg/mL, P = 0.03). Moreover, in on-line HDF, lower levels of C-reactive protein (5.5 ± 5.5 versus 6.7 ± 6.1 mg/L, P = 0.03) and triglycerides (148 ± 77 versus 167 ± 87 mg/dL, P = 0.008) and increased HDL cholesterol (49.2 ± 12.7 versus 44.7 ± 12.4 mg/dL, P = <0.0001) were observed. The asymmetric dimethylarginine level was not significantly affected (0.97 ± 0.4 versus 0.84 ± 0.37 µmol/L). Erythropoietin and phosphate binders' doses could be reduced. CONCLUSIONS: On-line high-efficiency HDF resulted in enhanced removal and lower basal levels of small, medium-sized and protein-bound solutes, which are markers or causative agents of uraemic pathologies, mainly inflammation, secondary hyperparathyroidism and dyslipidaemia. This may contribute to reducing uraemic complications and possibly to improving patient survival.