| 1. |
- Lind, Liza, 1984, et al.
(författare)
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CXCL11 production in cerebrospinal fluid distinguishes herpes simplex meningitis from herpes simplex encephalitis
- 2017
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: The closely related herpes simplex viruses 1 and 2 can cause inflammations of the central nervous system (CNS), where type 1 most often manifest as encephalitis (HSE), and type 2 as meningitis (HSM). HSE is associated with severe neurological complications, while HSM is benign in adults. We proposed that studying the chemokine and cytokine production in cerebrospinal fluid (CSF) and serum could indicate why two closely related viruses exhibit different severity of their accompanied CNS inflammation. Methods: Secretion patterns of 30 chemokines and 10 cytokines in CSF of adult patients with acute HSE (n = 14) and HSM (n = 20) in the initial stage of disease were analyzed and compared to control subjects without viral central nervous system infections and to levels in serum. Results: Most measured chemokines and cytokines increased in CSF of HSE and HSM patients. Overall, the CSF chemokine levels were higher in CSF of HSM patients compared to HSE patients. However, only five chemokines reached levels in the CSF that exceeded those in serum facilitating a positive CSF-serum chemokine gradient. Of these, CXCL8, CXCL9, and CXCL10 were present at high levels both in HSE and HSM whereas CXCL11 and CCL8 were present in HSM alone. Several chemokines were also elevated in serum of HSE patients but only one in HSM patients. No chemokine in- or efflux between CSF and serum was indicated as the levels of chemokines in CSF and serum did not correlate. Conclusions: We show that HSM is associated with a stronger and more diverse inflammatory response in the CNS compared to HSE in the initial stage of disease. The chemokine patterns were distinguished by the exclusive local CNS production of CXCL11 and CCL8 in HSM. Inflammation in HSM appears to be restricted to the CNS whereas HSE also was associated with systemic inflammation.
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| 2. |
- Brynjolfsson, Siggeir, et al.
(författare)
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Long-lived plasma cells in mice and men
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Even though more than 30 years have passed since the eradication of smallpox, high titers of smallpox-specific antibodies are still detected in the blood of subjects vaccinated in childhood. In fact, smallpox-specific antibody levels are maintained in serum for more than 70 years. The generation of life-long immunity against infectious diseases such as smallpox and measles has been thoroughly documented. Although the mechanisms behind high persisting antibody titers in the absence of the causative agent are still unclear, long lived plasma cells (LLPCs) play an important role. Most of the current knowledge on LLPCs is based on experiments performed in mouse models, although the amount of data derived from human studies is increasing. As the results from mouse models are often directly extrapolated to humans, it is important to keep in mind that there are differences. These are not only the obvious such as the life span but there are also anatomical differences, for instance the adiposity of the bone marrow (BM) where LLPCs reside. Whether these differences have an effect on the function of the immune system, and in particular on LLPCs, are still unknown. In this review, we will briefly discuss current knowledge of LLPCs, comparing mice and humans. © 2007 - 2018 Frontiers Media S.A.
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| 3. |
- Jons, Daniel, 1974, et al.
(författare)
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Follow-up after infectious mononucleosis in search of serological similarities with presymptomatic multiple sclerosis
- 2021
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 56
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Tidskriftsartikel (refereegranskat)abstract
- Background: : A two- to three-fold increase in the risk of multiple sclerosis (MS) after infectious mononucleosis (IM) has been observed in cohort and case control studies. However, this association has not been investigated prospectively from IM. It remains to be determined whether long-term immunospecific sequelae with features consistent with presymptomatic MS occur after IM. Methods: : Sera were obtained from individuals with acute IM from 2003-2007 (n = 42) and from the same individuals at a follow-up (FU) study approximately 10 years after IM. These were assayed for antibodies against a variety of Epstein-Barr virus (EBV) antigens, including gp350, a novel recombinant glycoprotein from the EBV envelope. Similarly, single-protein antigens were used to assess measles and varicella-zoster reactivity (Ncore and varicella-zoster glycoprotein E [VZVgE]). The FU study also included cerebrospinal fluid (CSF) samples from 21 of these individuals to test for IgG antibodies against the same viral antigens. As controls, CSF and serum samples were obtained from 15 EBV-seropositive volunteers who denied a history of IM, and serum samples were obtained from 24 EBV-seropositive blood donors. Anti-gp350, anti-Ncore and anti-VZVgE IgG levels were also analysed in sera and CSF samples from 22 persons with MS. Results: : The FU assays showed higher anti-gp350 IgG (p = 0.007, univariate) than among healthy controls, with no difference in serum anti-VCA or anti-EBNA1 IgG levels and no difference in anti-gp350 in the CSF samples. Anti-Ncore IgG and anti-VZVgE were higher in acute IM samples (p < 0.001 and p < 0.0001, respectively) than at FU, although anti-Ncore remained heightened in an age-adjusted analysis at FU (p = 0.014) compared to the control group. In the MS group, the serum anti-gp350 and anti-Ncore IgG levels were significantly higher than among the control group, but the anti-VZVgE levels were not. The CSF anti-gp350 and VZVgE levels were slightly higher among persons with MS than among the control group, whereas anti-Ncore IgG was markedly higher in persons with MS than in the control group. Conclusion: : In the present study IM showed certain similarities with MS. Increased anti-gp350 reactivity persisted more than a decade after IM, reminiscent of the established increased anti-EBV reactivity in presymptomatic MS. Acute IM was associated with increased anti-measles and anti-VZV immunoreactivity, similar to the MRZ reaction in MS, with some evidence suggesting that this measles reactivity persisted after a decade.
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| 4. |
- Persson Berg, Linn, 1984, et al.
(författare)
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Recombinant Epstein-Barr virus glycoprotein 350 as a serological antigen
- 2020
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Ingår i: Journal of Virological Methods. - : Elsevier BV. - 0166-0934. ; 284
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Tidskriftsartikel (refereegranskat)abstract
- Epstein-Barr virus (EBV) glycoprotein 350 (gp350) is the most abundant glycoprotein expressed on the EBV envelope, the major target for neutralizing antibodies and also essential for virion attachment to B lymphocytes. Several studies have addressed EBV gp350 as a vaccine candidate, but less commonly as a potential antigen for serological assays. The aim of the current study was to develop a diagnostic tool to quantify EBV gp350-specific IgG in previously EBV-infected individuals. A construct encoding the extracellular domain of EBV gp350 (amino acid (aa) 1-860) was developed for expression in Chinese hamster ovary cells. Serum samples (n = 360) with known IgG serostatus against viral capsid antigen (VCA) and Epstein-Barr nuclear antigen 1 (EBNA1) were divided into three groups based on the differences in their serostatus: VCA + EBNA1+ (n = 120), VCA + EBNA1-(n = 120) and VCA-EBNA1-(n = 120). The samples were analyzed by indirect ELISA using recombinant EBV gp350 aa 1-860 as antigen. A clear majority, 108 of the 120 VCA + EBNA1+ samples, had detectable EBV gp350-specific IgG. Of the 120 VCA + EBNA1-samples, 79 had detectable EBV gp350-specific IgG. Only 2 of the 120 VCA-EBNA1-samples had detectable EBV gp350-specific IgG. The results reported here show that use of the EBV gp350 aa 1-860 ELISA can serve as a sensitive method for EBV-specific IgG detection in serum samples.
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| 5. |
- Persson Berg, Linn, 1984, et al.
(författare)
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Serum IgG levels to Epstein-Barr and measles viruses in patients with multiple sclerosis during natalizumab and interferon beta treatment
- 2022
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Ingår i: Bmj Neurology Open. - : BMJ. - 2632-6140. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with multiple sclerosis (MS) demonstrate higher seroprevalence of Epstein-Barr virus (EBV) and increased anti-EBV IgG levels in serum compared with healthy controls. Intrathecal antibody production to measles virus (MeV) is a common finding in patients with MS. Objective To measure serum IgG reactivity to EBV glycoprotein 350 (gp350) and MeV nucleocapsid protein (N-CORE) in patients with MS and healthy controls and to determine if reactivity changed in patients during interferon beta (IFN beta) and/or natalizumab (NAT) treatment. A secondary aim was to determine the seroprevalence of EBV in patients and controls. Methods Patients with MS (n=728) were included from the Swedish pharmacovigilance study for NAT. Paired serum samples from 714 patients drawn before and during NAT treatment and paired samples from 170 patients during prior IFN beta treatment were analysed. In total, 156 patients were included in both groups. Samples from 144 matched blood donors served as controls. Indirect ELISA was applied using recombinant EBVgp350 and MeV N-CORE as antigens. EBVgp350 IgG seronegative samples were also analysed using EBV nuclear antigen 1 and viral capsid antigen (VCA). Results Patients with MS showed higher serum levels of anti-EBVgp350 and anti-MeV N-CORE IgG compared with controls. During NAT treatment, the levels of anti-EBVgp350 and anti-MeV N-CORE IgG declined, compared with the relatively stable levels noted during prior IFN beta treatment. Ten patients failed to demonstrate anti-EBVgp350 IgG but did show detectable anti-VCA IgG, indicating EBV seropositivity. In contrast, 10/144 controls were EBV seronegative. Conclusions Treatment with NAT, which is considered a selective immunosuppressive agent with a compartmentalised effect on the central nervous system, appeared to be associated with a moderate decrease in circulating IgG levels to EBVgp350 and MeV N-CORE. All patients with MS were EBV IgG seropositive, supporting the potential role of EBV in the pathogenesis of MS.
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| 6. |
- Persson Berg, Linn, 1984
(författare)
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Viral proteins as serological antigens - Development and clinical applications
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Serological methods are based on the detection of antibodies and antigens in mainly serum but also in other body fluids such as cerebrospinal fluid (CSF). Conventional whole virus antigens are widely used in viral serological assays. These antigens usually contain a mixture of proteins from the virus of interest together with residual cell components from antigen production, which can cause diagnostic problems with cross-reactive antibodies between closely related viruses and antibodies that bind to cellular components. The methods can become more specific by using antigens based on recombinant single viral proteins that differ between closely related viruses but to which the immune system reacts strongly (immunodominant proteins). The aim of the research has been to develop specific serological assays to detect antibodies to varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and measles virus (MeV). This has been accomplished by recombinantly producing single, specific, immunodominant viral proteins, VZV glycoprotein E (gE), EBV glycoprotein 350 (gp350) and the core part of the MeV nucleocapsid protein (NCORE), for use as serological antigens in enzyme-linked immunosorbent assay (ELISA). In Paper I, we show that VZVgE functions well as ELISA antigen to detect anti-VZVgE IgG antibodies. The antigen has thereafter been used in the routine diagnostics at the Department of Clinical Microbiology, Sahlgrenska University Hospital. In Paper II, we demonstrate that EBVgp350 performs well as serological antigen in ELISA for the detection of anti-EBVgp350 IgG. In Paper III, we found that patients with multiple sclerosis (MS) and their clinically healthy siblings with similar MS findings in CSF, i.e. a suspect hyperimmune phenotype, still show an increased IgG response to MeV in both serum and CSF compared with healthy controls when the previously used complex MeV whole virus antigen was replaced with MeV NCORE. Our results indicate that the reactivity is indeed specific and not caused by cross-reacting autoantibodies to cellular proteins. In Paper IV, patients with MS show higher IgG levels in both serum and CSF to MeV and EBVgp350 compared with healthy controls. In addition, we observed that patients with serologically verified acute infectious mononucleosis have higher serum IgG levels to EBVgp350 at follow-up after 10 years compared with healthy controls, suggesting that EBV-induced mononucleosis affects the immune system in a powerful and long-lasting way. In Paper V, patients with MS treated with interferon beta (IFNβ) had higher anti-EBVgp350 and anti-MeV NCORE IgG levels in serum compared with healthy blood donors. Following initiation of treatment with the monoclonal antibody natalizumab, patients' serum IgG levels decreased against both antigens, whereas levels were relatively stable during previous IFNβ treatment. Another finding was that all 728 patients with MS in the study were EBV IgG seropositive while 10 of the 144 blood donors in the control group were EBV IgG seronegative. This finding further strengthens the potential role of EBV in the pathogenesis of MS. The developed ELISA methods can, through increased specificity, offer new diagnostic possibilities for detecting antibodies to EBV, VZV and MeV in viral infections, for control of immunity after infection/vaccination, in epidemiological investigations and in autoimmune diseases such as MS.
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| 7. |
- Widgren, K, et al.
(författare)
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Severe chickenpox disease and seroprevalence in Sweden - implications for general vaccination.
- 2021
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Ingår i: International journal of infectious diseases : IJID. - : Elsevier BV. - 1878-3511 .- 1201-9712. ; 111, s. 92-98
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Tidskriftsartikel (refereegranskat)abstract
- To describe the current panorama of severe chickenpox disease and seroprevalence in Sweden, as a basis for the approaching decision on universal vaccination.We included patients discharged with an International Classification of Diseases, 10th revision-code for chickenpox (B01.1-9) in eight pediatric and infectious diseases departments in Stockholm and Gothenburg in 2012-2014 and reviewed their medical charts. Further, residual serum samples collected from 16 laboratories across Sweden were analyzed for varicella zoster IgG-antibodies to investigate the age-specific seroprevalences.In all, 218 children and 46 adults were included in the hospital-based study, 87.2% of children and 63.0% of adults had complications. An underlying condition was not associated with an increased risk for complication. In children dehydration (31.7%), bacterial skin infections (29.8%) and neurological involvement (20.6%) were most frequent complications. Among adult cases, 63 % were born abroad. The seroepidemiological analysis included 957 patient samples. Seroprevalence was 66.7% at 5 years and 91.5% at 12 years. Infants and adolescents/adults were overrepresented among admitted patients compared to seroprevalence data.Half of all complications in hospitalized chickenpox cases was seen in previously healthy children, which supports universal childhood vaccination. Adult migrants was a risk group for chickenpox hospitalization. Age-specific seroprevalence was similar to neighboring countries.
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