The P2X7 receptor (P2X7R) is a key pro-inflammatory plasma membrane receptor responsible for NLRP3 inflammasome activation and IL-1β release. Various inflammatory plasma membrane receptors (e.g., IL-1 type I receptor, TNF type I and II receptors, IL-2 receptor) are shed under different pathophysiological conditions. In the present study, we show that the full length P2X7R is released into circulation in patients as well as in healthy subjects. Blood levels of shed P2X7R (sP2X7R) correlate to those of the inflammatory marker C reactive protein (CRP). Blood sP2X7R ranged from 16.74 to 82.17 ng/L, mean ± SE 40.97 ± 3.82 ( n = 26) in healthy subjects, from 33.1 to 484.0 ng/L, mean ± SE 114.78 ± 12.22 ( n = 45) in patients with CRP <3 mg/L, and from 63.65 to 1092.3 ng/L, mean ± SE 204.2 ± 30.94 ( n = 42) in patients with CRP >3 mg/L. sP2X7R in plasma was largely associated to microvesicles/microparticles. Peripheral blood monocytes from healthy subjects released sP2X7R upon stimulation with the semi-selective P2X7R agonist benzoyl ATP. These data show that the P2X7R can be released into circulation, and that its blood levels increase in various disease conditions.
Hyperprolactinemia can have different causes: physiological, pharmacological, and pathological. When investigating the etiology of hyperprolactinemia, clinicians need to be aware of several conditions leading to misdiagnosis. The most popular pitfalls are: acute physical and psychological stress, macroprolactin, hook effect, even though antibodies interferences and biotine use have to be considered. A 52-year-old woman was referred to Endocrinology clinic for oligomenorrhoea and headache. She worked as a butcher. Hormonal evaluation showed very high PRL (305 ng/ml, reference interval: <24 ng/ml) measured with the ECLIA immunoassay analyzer Elecsys 170. The patient’s pituitary MRI was normal and macroprolactin was normal. Hormonal workup showed LH: 71.5 mU/ml (2–10.9 mU/ml), FSH: 111.4 mU/ml (3.9–8.8 mU/ml), Estradiol: 110.7 pg/mL (27–122 pg/ml). Since an interference was suspected, the sample was sent to another laboratory using a different assay. After antibody blocking tubes treatment (Heterophilic Blocking Tube, Scantibodies) PRL was 28.8 ng/ml (reference interval < 29.2 ng/ml). Analytical interference should be suspected when assay results are not consistent with the clinical picture. Endogenous antibodies (EA) include heterophile, human anti-animal, autoimmune and other nonspecific antibodies, and rheumatoid factors, that have structural similarities and can cross-react with the antibodies employed by the immunoassay, causing hyperprolactinemia misdiagnosis. The patient’s job (butcher), led us to suspect the presence of anti-animal antibodies. Clinicians should also carefully investigate the use of supplements. Biotin can falsely increase hormone concentration in competitive assays. Many clinicians are still not informed about these pitfalls that are not mentioned in some recent reviews on PRL measurement.
Background: Development and worldwide availability of safe and effective vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to fight severe symptoms of coronavirus disease 2019 (COVID-19) and block the pandemic have been a great achievement and stimulated researchers on understanding the efficacy and duration of different vaccine types.Methods: We investigated the levels of anti-SARS-CoV-2 antibodies (IgG) and neutralizing antibodies (NAbs) in 195 healthy adult subjects belonging to the staff of the University-Hospital of Ferrara (Italy) starting from 15 days up to 190 days (about 6 months) after the second dose of the BNT162b2 (Pfizer–BioNTech) mRNA-based vaccine (n = 128) or ChAdOx1 (AstraZeneca) adenovirus-based vaccine (n = 67) using a combined approach of serological and genomics investigations.Results: A strong correlation between IgG and NAb levels was detected during the 190 days of follow-up (r2 = 0.807; p < 0.0001) and was confirmed during the first 90 days (T1) after vaccination (r2 = 0.789; p = 0.0001) and 91–190 days (T2) after vaccination (r2 = 0.764; p = 0.0001) for both vaccine types (r2 = 0.842; p = 0.0001 and r2 = 0.780; p = 0.0001 for mRNA- and adenovirus-based vaccine, respectively). In addition to age (p < 0.01), sex (p = 0.03), and type of vaccine (p < 0.0001), which partially accounted for the remarkable individual differences observed in the antibody levels and dynamics, interesting genetic determinants appeared as significant modifiers of both IgG and NAb responses among the selected genes investigated (TP53, rs1042522; APOE, rs7412/rs429358; ABO, rs657152; ACE2, rs2285666; HLA-A rs2571381/rs2499; CRP, rs2808635/rs876538; LZTFL1, rs35044562; OAS3, rs10735079; SLC6A20, rs11385942; CFH, rs1061170; and ACE1, ins/del, rs4646994). In detail, regression analysis and mean antibody level comparison yielded appreciable differences after genotype stratification (P1 and P2, respectively, for IgG and NAb distribution) in the whole cohort and/or in the mRNA-based vaccine in the following genes: TP53, rs1042522 (P1 = 0.03; P2 = 0.04); ABO, rs657152 (P1 = 0.01; P2 = 0.03); APOE, rs7412/rs429358 (P1 = 0.0018; P2 = 0.0002); ACE2, rs2285666 (P1 = 0.014; P2 = 0.009); HLA-A, rs2571381/rs2499 (P1 = 0.02; P2 = 0.03); and CRP, rs2808635/rs876538 (P1 = 0.01 and P2 = 0.09).Conclusion: High- or low-responsive subjects can be identified among healthy adult vaccinated subjects after targeted genetic screening. This suggests that favorable genetic backgrounds may support the progression of an effective vaccine-induced immune response, though no definite conclusions can be drawn on the real effectiveness ascribed to a specific vaccine or to the different extent of a genotype-driven humoral response. The interplay between data from the polygenic predictive markers and serological screening stratified by demogeographic information can help to recognize the individual humoral response, accounting for ethnic and geographical differences, in both COVID-19 and anti-SARS-CoV-2 vaccinations.
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