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Background and purpose: To elucidate the role of human herpesvirus-6 (HHV-6) in the development of multiple sclerosis (MS). Patients and methods: Nine patients with MS and with acute or chronic HHV-6 infection were evaluated. Results: Intrathecal antibody production to HHV-6 and oligoclonal IgG bands in the cerebrospinal fluid (CSF) was observed in two patients with a clinically definite MS and chronic HHV-6 infection (based on the presence of HHV-6 specific antibodies in the CSF). A temporal association between the symptoms of clinically possible MS and acute primary HHV-6A infection (based on avidity of HHV-6 specific antibodies) was observed in two patients. Conclusions: Human herpesvirus-6 infection may be an associated agent in some MS cases. Viral studies are needed to identify a possible viral etiology and give specific therapy. [ABSTRACT FROM AUTHOR]

Objective: To study genetic variants and their function within genes coding for complement receptors in pre‐eclampsia. Design: A case–control study. Setting: Pre‐eclampsia is a common vascular disease of pregnancy. The clearance of placenta‐derived material is one of the functions of the complement system in pregnancy. Population: We genotyped 500 women with pre‐eclamptic pregnancies and 190 pregnant women without pre‐eclampsia, as controls, from the FINNPEC cohort, and 122 women with pre‐eclamptic pregnancies and 1905 controls from the national FINRISK cohort. Methods: The functional consequences of genotypes discovered by targeted exomic sequencing were explored by analysing the binding of the main ligand iC3b to mutated CR3 or CR4, which were transiently expressed on the surface of COS‐1 cells. Main outcome measures: Allele frequencies were compared between pre‐eclamptic pregnancies and controls in genetic studies. The functional consequences of selected variants were measured by binding assays. Results: The most significantly pre‐eclampsia‐linked CR3 variant M441K (P = 4.27E‐4, OR = 1.401, 95% CI = 1.167–1.682) displayed a trend of increased adhesion to iC3b (P = 0.051). The CR4 variant A251T was found to enhance the adhesion of CR4 to iC3b, whereas W48R resulted in a decrease of the binding of CR4 to iC3b. Conclusions: Results suggest that changes in complement‐facilitated phagocytosis are associated with pre‐eclampsia. Further studies are needed to ascertain whether aberrant CR3 and CR4 activity leads to altered pro‐ and anti‐inflammatory cytokine responses in individuals carrying the associated variants, and the role of these receptors in pre‐eclampsia pathogenesis. Genetic variants of complement receptors CR3 and CR4 have functional consequences that are associated with pre‐eclampsia. Genetic variants of complement receptors CR3 and CR4 have functional consequences that are associated with pre‐eclampsia. This article includes Author Insights, a video abstract available at https://vimeo.com/bjog/authorinsights16660 [ABSTRACT FROM AUTHOR]

Human herpesvirus 6 (HHV-6) has been linked to the pathogenesis of multiple sclerosis (MS). HHV-6 antibodies in serum and cerebrospinal fluid (CSF) of 27 patients with clinically definite MS (CDMS) were compared with age- and sex-matched controls, including various other neurological diseases and symptoms (OND). In addition, we studied a series of 19 patients with clinically or laboratory supported possible MS (CPMS). Seroprevalence to HHV-6A was 100% in patients with MS, both in CDMS and CPMS, compared to 69.2% in patients with OND (P = .001 and .007). The mean immunoglobulin G (IgG) titers were significantly higher in patients with CDMS and CPMS than in controls (P = .005 and .00002). The proportion of acute primary infections without CSF involvement was similar in all groups; however, primary infections with intrathecal HHV-6 antibody production were more frequent in MS. In CSF, HHV-6A-specific antibodies were present in three (11.5%) and four (21.1%) patients with CDMS and CPMS, compared to none with OND (P = .06 and .01, respectively). Serological suggestions to HHV-6A infection occurred more often in both CDMS and CPMS than in OND (14.8% versus 21.1% versus 3.8%). We conclude that a subpopulation of MS patients, and even a greater proportion of possible MS subjects, has serological evidence of HHV-6A infection, which might provide new markers for diagnosis and therapy. [ABSTRACT FROM AUTHOR]