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Hepatitis B (HB) infection is a major global health problem. There is limited knowledge about HB vaccination‐induced immune memory responses. We compared the frequency of CD8+ memory T cell subsets between responders (RSs) and non‐responders (NRs) to HB vaccination. Blood samples were collected from RSs and NRs. PBMCs were cultured in the presence of Hepatitis B surface antigens (HBsAg) and PHA for 48 h to restimulate CD8+ memory T cells and T cell memory subsets were detected by flow cytometry using memory cell markers. The frequency of TEM, TCM, and TCMhi was significantly higher in responders compared to non‐responders (p = 0.024, 0.022, and 0.047, respectively). Additionally, we report a positive correlation between the frequency of TEM cells in RSs with age and anti‐HBsAb level (p = 0.03 and rs = 0.5; p = 0.01 and rs = 0.06). Responders display a higher level of CD8+ T cell‐mediated immunity. Therefore, we suggest a possible defect in the formation of immunological CD8+ memory T cells in NRs and it may reduce antibody production compared to the RSs, although more experiments are needed. [ABSTRACT FROM AUTHOR]

Lyme borreliosis, caused by Borrelia burgdorferi sensu lato, is the most common tickborne disease. Its neuronal form, neuroborreliosis, comprises 3 to 38% of borreliosis cases in Europe. Borrelia outer surface proteins and virulence factors, OspE and BBK32, have been previously reported to help cause infection by promoting attachment to human host epithelial cells and evading complement attack. We assessed the serological responses to BBK32 and OspE in 19 individuals diagnosed with neuroborreliosis to see whether antibodies that could both target the bacteria and neutralize the virulence mechanisms on the microbial surface emerge. Results evaluate levels of total protein, IgG and the chemokine CXCL13, a determinant for B‐cell recruitment during neuroinflammation, in patients' cerebrospinal fluid samples. Antibody levels against BBK32 and OspE correlated with those against VlsE, a well‐characterized diagnostic serological marker of the disease. A dual serological profile of the patients was observed. K‐means clustering split the cohort into two discrete groups presenting distinct serological and CNS responses. One group contained young patients with low levels of anti‐BBK32 and OspE antibodies. The other group showed stronger responses, possibly following prolonged infections or reinfections. Additionally, we assessed anti‐ganglioside antibodies that could cause autoimmunity or complement dysregulation but observed that they did not correlate with neuroborreliosis in our patient cohort. The dual nature of antibody responses against the virulence factors BBK32 and OspE in neuroborreliosis patients may suggest the necessity of repeated exposures for efficient immune responses. Better protection could be achieved if the virulence factors were formulated into vaccines. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to investigate the role of genetic variants in complement proteins in pre‐eclampsia. Design: In a case–control study involving 609 cases and 2092 controls, five rare variants in complement factor H (CFH) were identified in women with severe and complicated pre‐eclampsia. No variants were identified in controls. Setting: Pre‐eclampsia is a leading cause of maternal and fetal morbidity and mortality. Immune maladaptation, in particular, complement activation that disrupts maternal‐fetal tolerance leading to placental dysfunction and endothelial injury, has been proposed as a pathogenetic mechanism, but this remains unproven. Population: We genotyped 609 pre‐eclampsia cases and 2092 controls from FINNPEC and the national FINRISK cohorts. Methods: Complement‐based functional and structural assays were conducted in vitro to define the significance of these five missense variants and each compared with wild type. Main outcome measures: Secretion, expression and ability to regulate complement activation were assessed for factor H proteins harbouring the mutations. Results: We identified five heterozygous rare variants in complement factor H (L3V, R127H, R166Q, C1077S and N1176K) in seven women with severe pre‐eclampsia. These variants were not identified in controls. Variants C1077S and N1176K were novel. Antigenic, functional and structural analyses established that four (R127H, R166Q, C1077S and N1176K) were deleterious. Variants R127H and C1077S were synthesised, but not secreted. Variants R166Q and N1176K were secreted normally but showed reduced binding to C3b and consequently defective complement regulatory activity. No defect was identified for L3V. Conclusions: These results suggest that complement dysregulation due to mutations in complement factor H is among the pathophysiological mechanisms underlying severe pre‐eclampsia. [ABSTRACT FROM AUTHOR]