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This study monitored the anti-spike-receptor-binding domain (RBD) and neutralizing antibodies induced by the Pfizer/BioNTech mRNA BNT162b2 vaccine in a cohort of 163 healthcare workers aged =60 years. We have taken advantage of two study groups, both of whom received the first two doses in the same time window, but Group 1 (54 HCWs) received the third dose 2 months before Group 2 (68 HCWs) did. The cohorts were monitored from the 12th day after the first vaccine dose up to 1 month after the third vaccine dose for a total of eight time points and about 1 year of surveillance (T1 = 12 days after the first dose; T2 = 10 days after the second dose; T3 = 1 month after the second dose; T4 = 3 months after the second dose; T5 = 4 months after the second dose; T6 = 5 months after the second dose; T7 = 7months after the second dose; T8 = 1 month after the third dose for Group 1; T8* = 9 months after the second dose forGroup 2; T9 = 1 month after the third dose for Group 2). The mean value of anti-spike antibodies decreased faster over time, but at T7, its declinewas significantly slowed (T7 vs. T8*). After the third dose, the anti-spike titer rose about 34-fold (T7 vs. T8 and T8* vs. T9) and the booster improved the anti-spike titer by about three times compared with that of the second dose (T3 vs. T8 and T3 vs. T9), and no difference was noted between the two groups. The neutralizing titer was evaluated at T3, T7, T8, and T9. Anti-spike and neutralizing antibodies were found to be strongly correlated (r2 = 0.980; p < 0.001). At T3, 70% of the participants had a neutralizing antibody titer >91% of total anti-spike antibodies that increased to 90% after the third dose (T8 and T9). However, when the anti-spike titer reached its lowest value (T7), the neutralizing antibody levels decreased even further, representing only 44% of total anti-spike antibodies (p < 0.0001). Our findings show that the third vaccine dose improves the humoral response, but the wane of the anti-spike and neutralizing antibody titers over time is more marked in the neutralizing antibodies. [ABSTRACT FROM AUTHOR]

Clinical spectrum of hepatitis C virus (HCV)‐related cryoglobulinemia varies from an asymptomatic presentation to severe vasculitis and lymphoma. A recent study in HCV‐negative patients suggests that low cryoglobulins (CGs) levels are responsible for severe renal and neurological complications. The aim of this study was to identify a panel of serological biomarkers associated with low levels of CGs in HCV‐positive patients. We studied a population of 79 untreated patients with chronic HCV infection: 13 naïve patients without CGs; 28 patients with asymptomatic mixed cryoglobulinemia (MC) and low levels of CGs (16/28 with polyclonal type III and 12/28 with microheterogeneous type III CGs); 38 patients with symptomatic MC and high levels of type II CGs. Serum samples were collected and examined for rheumatoid factor (RF) IgG and IgM, free light chains (FLCs) and C3 and C4 complement components. We found that RF‐IgG and IgM, free k chains and k+λ were increased while C4 component was reduced, both in symptomatic and asymptomatic patients. Our results suggest that, even in absence of MC symptoms, the low levels of CGs may represent a trigger of activation for immune system in course of HCV infection. The identification of a correlated biomarkers panel could improve the clinical management of these patients and pave the way for target treatment strategies. © 2018 BioFactors, 45(3):318–325, 2019 [ABSTRACT FROM AUTHOR]

Cryoglobulins are immunoglobulins that precipitate in serum at temperatures below 37°C and resolubilize upon warming. The clinical syndrome of cryoglobulinemia usually includes purpura, weakness, and arthralgia, but the underlying disease may also contribute other symptoms. Blood samples for cryoglobulin are collected, transported, clotted and spun at 37°C, before the precipitate is allowed to form when serum is stored at 4°C in a Wintrobe tube for at least seven days. The most critical and confounding factor affecting the cryoglobulin test is when the preanalytical phase is not fully completed at 37°C. The easiest way to quantify cryoglobulins is the cryocrit estimate. However, this approach has low accuracy and sensitivity. Furthermore, the precipitate should be resolubilized by warming to confirm that it is truly formed of cryoglobulins. The characterization of cryoglobulins requires the precipitate is several times washed, before performing immunofixation, a technique by which cryoglobulins can be classified depending on the characteristics of the detected immunoglobulins. These features imply a pathogenic role of these molecules which are consequently associated with a wide range of symptoms and manifestations. According to the Brouet classification, Cryoglobulins are grouped into three types by the immunochemical properties of immunoglobulins in the cryoprecipitate. The aim of this paper is to review the major aspects of cryoglobulinemia and the laboratory techniques used to detect and characterize cryoglobulins, taking into consideration the presence and consequences of cryoglobulinemia in Hepatitis C Virus (HCV) infection. [ABSTRACT FROM AUTHOR]

Background: The development of non-invasive procedure to determine HER2 status may represent a powerful method for monitoring disease progression and response to the treatment. Methods: Serum samples and RNA from peripheral blood were evaluated in 85 breast cancer patients (49 HER2 positive and 36 HER2 negative) and 22 healthy controls. HER2 mRNA levels were measured by real-time quantitative PCR (QPCR) and serum HER2 protein by immunoenzimatic assay (EIA). ROC curve analyses were used to determine the optimal cut off values. Results: A statistically significant difference was detected for both QPCR and EIA in HER2 positive patients as compared with both healthy controls and HER2 negative tumours. QPCR showed a 91% (CI95%: 84%–98%) specificity and a 78% (CI95%: 68%–88%) sensitivity for an optimal cut off value of 4.74. The optimal cut off value for EIA was 22 ng/ml yielding a 95% (CI95%: 90%–100%) specificity and a 59% (CI95%: 48%–70%) sensitivity. The QPCR assay was slightly less specific than EIA in discriminating HER2 positive breast cancers from HER2 negative tumours (78% CI95%: 69%–87% versus 86% CI95%: 79%–93%), but it was more sensitive (76% CI95%: 67%–85% versus 55% CI95%: 44%–66%). Conclusions: Our results indicate that QPCR performs better than EIA in the determination of HER2 status of breast cancer patients and could be useful in monitoring the disease during follow up. [ABSTRACT FROM AUTHOR]

Steroid 21-hydroxylase deficiency is present in more than 90% of patients with congenital adrenal hyperplasia (CAH), an inherited metabolic disorder of adrenal steroidogenesis. Impaired enzymatic activity leads to the accumulation of metabolic intermediates (progesterone and 17-hydroxyprogesterone), which results in excessive androgen production and varied signs of virilisation. CYP21A2 is an active gene and encodes for the steroid 21-hydroxylase enzyme, whereas CYP21A1P is an inactive pseudogene that contains a series of deleterious mutations. The major part of disease- causing mutations in CYP21A2 alleles are CYP21A1P-derived sequence transferred to the active gene by macro or microconversion events. Only around 5% of all disease-causing CYP21A2 alleles harbour rare mutations that do not originate from the pseudogene. In this report, we report the characterisation of two novel CYP21A2 missense mutations (p.H119R and p.I194N) found in two unrelated Italian patients with nonclassic (NC) CAH clinical diagnosis. Functional in vitro assays for mutagenized CYP21 enzymes were performed in transiently transfected mammalian cells to test the residual enzyme activity and the apparent kinetic values. The residual activities obtained for p.H119R and p.I194N mutants allowed to classify them as NC-CAH associated mutations. These results correlate with the rate of severity of the patients' disease. Finally, the new p.H119R and p.I194N mutations should be included in the panel of those already listed for association with the NC form of 21-hydroxylase deficiency. © 2009 IUBMB IUBMB Life 61(3): 229–235, 2009 [ABSTRACT FROM AUTHOR]

Background: Patients with type 1 diabetes (T1DM) present lower serum free IGF and IGFBP-3 values than healthy people. T1DM patients often present with associated autoimmune diseases such as thyroiditis or coeliac disease, and over time they frequently develop proliferative retinopathy, neuropathy or nephropathy in different combinations., Objective: The aim of this study was to evaluate the effect of two associated autoimmune diseases or three diabetic complications on the serum free IGF-I or IGFBP-3 levels in T1DM patients, who also have a family history of T1DM. Design. 246 T1DM patients were enrolled, and then subdivided into groups according to diabetic complications or associated autoimmune diseases. Demographic and clinical data were recorded. Serum free IGF-I and IGFBP-3 levels were determined by IRMA., Results: IGF-I and IGFBP-3 generally present correlated serum values as confirmed in this study. Those patients with autoimmune thyroiditis and coeliac disease presented with significantly lower serum values of IGFBP-3, whereas free IGF-I was significantly lower in patients with the different diabetic complications. Retinopathy presented a slightly significant reduction in serum free IGF-I, while neuropathy and nephropathy showed a more pronounced fall. The number of complications was related to progressively decreasing free IGF-I levels. T1DM family history was associated with lower serum free IGF-I concentrations. These findings were confirmed after correction for age, glycosylated haemoglobin levels, insulin treatment protocol, body mass index, serum creatinine and sex., Conclusion: Despite a direct correlation between serum free IGF-I and IGFBP-3, the correlation between the two molecules in patients with associated autoimmune diseases was lost, possibly due to different mechanisms of metabolic regulation.