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- Haghighi, Sara, et al.
(författare)
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Incidence of CSF abnormalities in siblings of multiple sclerosis patients and unrelated controls.
- 2000
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Ingår i: Journal of neurology. - 0340-5354 .- 1432-1459. ; 247:8, s. 616-22
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Tidskriftsartikel (refereegranskat)abstract
- We found that 19% (9/47) of healthy siblings of patients with clinically definite multiple sclerosis had an intrathecal immunological reaction with two or more 2 CSF-enriched oligoclonal bands (OCBs), in contrast to (4%) (2/50) unrelated healthy controls. Furthermore, in this group of nine healthy sibs the measles CSF IgG antibody titers were higher than that of the other sibs and that of controls. There were also differences in the serum titers for measles IgG antibody, which were higher in the group of all healthy sibs than in healthy volunteers, and (as with CSF titers) higher in the subgroup of healthy sibs with two or more 2 CSF-enriched OCBs than the other sibs. Thus a significant proportion of healthy siblings to MS patients have a partially hyperimmune condition similar to that occurring in MS, which in 19% manifested itself as an OCB reaction, in 9% as increased CSF measles IgG antibody titers, and in 21% as increased serum measles IgG antibody titers, these phenomena tending to occur in the same individuals. This condition is characterized by CSF-enriched OCBs with undefined specificity, although some increased antiviral reactivity is found both in the serum and CSF. While it needs further characterization, a genetic trait interacting with common infections is suggested. The recurrence risk of this condition is approximately five times higher than the 3-4% recurrence risk for manifest MS reported for sibs.
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- Haghighi, Sara, et al.
(författare)
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Increased CSF sulfatide levels and serum glycosphingolipid antibody levels in healthy siblings of multiple sclerosis patients
- 2013
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 326:1-2, s. 35-39
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Tidskriftsartikel (refereegranskat)abstract
- A proportion of healthy siblings of multiple sclerosis (MS) patients have an oligodonal immunological reaction in their cerebrospinal fluid (CSF) termed the "MS oligoclonal trait". The CSF levels of the major myelin glycosphingolipid sulfatide and serum antibodies against the glycosphingolipids sulfatide and galactosylceramide were recently reported to be increased in MS patients. We studied the levels of these substances in pairs of 46 patients and their 46 healthy siblings and 50 unrelated healthy blood donors (HBD). The sulfatide concentration in CSF was assayed by thin layer chromatography and immunostaining, and the concentration of galactosylceramide by densitometry after thin layer chromatography. Anti-glycosphingolipid antibody levels were assayed by ELISA. In the healthy siblings, the CSF sulfatide concentrations were markedly increased (p<0.001, age adjusted p = 0.025), and the serum IgM anti-GalCer antibodies were increased in healthy siblings compared with HBD (p = 0.02). The increased sulfatide or antibody levels did not co-segregate with the "MS oligoclonal trait" or the HLA-DR15 phenotype. In conclusion, a proportion of healthy siblings of MS patients have increased CSF sulfatide and anti-glycosphingolipid antibody levels, which may, analogous to the "MS oligoclonal trait", constitute an "MS glycosphingolipid endophenotype". Endophenotypes could potentially simplify the genetics of complex disorders
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- Haghighi, Sara, et al.
(författare)
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Myelin glycosphingolipid immunoreactivity and CSF levels in multiple sclerosis.
- 2012
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 125:1, s. 64-70
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Tidskriftsartikel (refereegranskat)abstract
- Objectives - Patients with multiple sclerosis were reported to harbour antibodies not only against proteins and glycoproteins but also against glycolipids, including sulfatide and galactosylceramide (GalCer), the two major glycosphingolipids of myelin. However, previous results were inconsistent concerning glycosphingolipid levels, antibody type, dominance of serum or Cerebrospinal fluid compartments and relationship to the multiple sclerosis (MS) course. Results - We hereby report that the cerebrospinal fluid levels of sulfatide were increased in patients with MS (n = 46) compared with controls (n = 50, P < 0.001). In addition, patients had higher serum IgM anti-glycosphingolipid titres than controls (P = 0.03 for sulfatide, <0.001 for GalCer), while the anti-glycosphingolipid IgM antibodies in the cerebrospinal fluid were essentially normal. However, in seven of 46 patients cerebrospinal fluid IgG antibodies against GalCer (P = 0.004) could be detected, which was not found in any of the control individuals, and this finding might mirror the occurrence of more specific B-cell clones behind the blood-brain barrier. Conclusions - The IgM immunoreactivity in serum did not show any relationship to the type of course or severity of MS, arguing against a phenomenon secondary to myelin damage. Thus, the IgM antibody findings are compatible with an early antigen challenge or autoimmunity associated with natural antibodies.
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- Jons, Daniel, 1974, et al.
(författare)
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Axonal injury in asymptomatic individuals preceding onset of multiple sclerosis
- 2022
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 9:6, s. 882-887
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Tidskriftsartikel (refereegranskat)abstract
- Axonal loss is the main cause of irreversible disability in multiple sclerosis (MS). Serum neurofilament light (sNfL) is a biomarker of axonal disintegration. In this nested case-control study, blood samples from 519 presymptomatic persons (age range 4-39 years) who later received an MS diagnosis showed higher sNfL concentrations than 519 matched controls (p < 0.0001), noticeable at least 10 years before clinical MS onset. Mean values for pre-MS and control groups were 9.6 pg/mL versus 7.4 pg/mL 0-5 years before onset, and 6.4 pg/mL versus 5.8 pg/mL 5-10 years before onset. These results support that axonal injury occurs early in MS pathogenesis.
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- Jons, Daniel, et al.
(författare)
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Seroreactivity against lytic, latent and possible cross-reactive EBV antigens appears on average 10 years before MS induced preclinical neuroaxonal damage
- 2023
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 1468-330X .- 0022-3050.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple sclerosis (MS) and presymptomatic axonal injury appear to develop only after an Epstein-Barr virus (EBV) infection. This association remains to be confirmed across a broad preclinical time range, for lytic and latent EBV seroreactivity, and for potential cross-reacting antigens. Methods: We performed a case-control study with 669 individual serum samples obtained before clinical MS onset, identified through cross-linkage with the Swedish MS register. We assayed antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18, glycoprotein 350 (gp350), the potential cross-reacting protein anoctamin 2 (ANO2) and the level of sNfL, a marker of axonal injury. Results: EBNA1 (latency) seroreactivity increased in the pre-MS group, at 15-20 years before clinical MS onset, followed by gp350 (lytic) seroreactivity (p=0.001-0.009), ANO2 seropositivity appeared shortly after EBNA1-seropositivity in 16.7% of pre-MS cases and 10.0% of controls (p=0.001).With an average lag of almost a decade after EBV, sNfL gradually increased, mainly in the increasing subgroup of seropositive pre-MS cases (p=8.10-5 compared with non-MS controls). Seropositive pre-MS cases reached higher sNfL levels than seronegative pre-MS (p=0.038). In the EBNA1-seropositive pre-MS group, ANO2 seropositive cases had 26% higher sNfL level (p=0.0026). Conclusions: Seroreactivity against latent and lytic EBV antigens, and in a subset ANO2, was detectable on average a decade before the appearance of a gradually increasing axonal injury occurring in the last decade before the onset of clinical MS. These findings strengthen the hypothesis of latent EBV involvement in the pathogenesis of MS.
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- Kneider, Maria, et al.
(författare)
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Sequence analysis of human rhinovirus aspirated from the nasopharynx of patients with relapsing-remitting MS.
- 2009
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 15:4, s. 437-42
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundUpper respiratory infections were reported to trigger multiple sclerosis relapses. A relationship between picornavirus infections and MS relapses was recently reported.ObjectiveTo evaluate whether human rhinovirus is associated with multiple sclerosis relapses and whether any particular strain is predominant.MethodNasopharyngeal fluid was aspirated from 36 multiple sclerosis patients at pre-defined critical time points. Reverse-transcriptase-PCR was performed to detect human rhinovirus-RNA. Positive amplicons were sequenced.ResultsWe found that rhinovirus RNA was present in 17/40 (43%) of specimens obtained at the onset of a URTI in 19 patients, in 1/21 specimens during convalescence after URTI in 14 patients, in 0/6 specimens obtained in 5 patients on average a week after the onset of an "at risk" relapse, occurring within a window in time from one week before to three weeks after an infection, and in 0/17 specimens obtained after the onset of a "not at risk" relapse not associated with any infection in 12 patients. Fifteen specimens from healthy control persons not associated with URTI were negative. The frequency of HRV presence in URTI was similar to that reported for community infections. Eight amplicons from patients represented 5 different HRV strains.ConclusionWe were unable to reproduce previous findings of association between HRV infections and multiple sclerosis relapses. HRV was not present in nasopharyngeal aspirates obtained during "at risk" or "not at risk" relapses. Sequencing of HRV obtained from patients during URTI did not reveal any strain with predominance in multiple sclerosis.
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| 9. |
- Mossberg, Natalia, et al.
(författare)
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Leukocyte oxygen radical production determines disease severity in the recurrent Guillain-Barré
- 2010
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Ingår i: Journal of Inflammation. - : Springer Science and Business Media LLC. - 1476-9255. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: The recurrent Guillain-Barré syndrome (RGBS) is characterized by at least two GBS episodes with intervening remission. In a previous study of monophasic GBS, we reported that the magnitude of oxygen radical production ("respiratory burst”) in peripheral blood leukocytes was inversely correlated to disease severity. The present study sought to establish a similar correlation in patients with RGBS. Methods: Oxygen radical production in leukocytes was induced by formyl-Met-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-Val- Met-NH2 (WKYMVM), or phorbol myristate acetate (PMA) and assessed by quantifying superoxide anion formed by the leukocyte NADPH oxidase. Results: Disease severity, assessed using the MRC score, was negatively correlated to superoxide anion production triggered by fMLF or WKYMVM (p = 0.001 and 0.002, respectively; n = 10). Superoxide anion production also was significantly lower in RGBS patients with incomplete recovery after stimulation with fMLF (p = 0.004) or WKYMVM (p = 0.003). Conclusion: We conclude that a lower respiratory burst in leukocytes is strongly associated with a severe course of RGBS
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- Mossberg, Natalia, et al.
(författare)
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Oxygen radical production and severity of the Guillain--Barré syndrome.
- 2007
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Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 0165-5728. ; 192:1-2, s. 186-91
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Tidskriftsartikel (refereegranskat)abstract
- The NADPH oxidase-dependent formation of reactive oxygen species ("oxygen radicals") by phagocytic cells constitutes an important part of the innate immune defence against microorganisms. Recent studies in animal models imply that a deficient function of the NADPH oxidase may be linked to the development of autoimmunity, but a link between oxygen radical production and severity of autoimmune disease in humans has not been established. We have examined the oxygen radical production in peripheral blood leukocytes from patients with the Guillain-Barré syndrome (GBS). Leukocytes from GBS patients in a stationary phase 1-5 years after their acute episode were activated by the formyl peptide receptor (FPR) ligand formyl-Met-Leu-Phe (fMLF) or the closely related formyl peptide like receptor 1 (FPRL1) ligand Trp-Lys-Tyr-Met-Val-Met-NH2 (WKYMVM). The patients were dichotomized according to severity by 1) the requirement of intensive care unit treatment and 2) the ability to walk independently after 3 months. Our data show that the amount of superoxide release following challenge with either of the two agonists fMLF and WKYMVM was significantly lower in patients requiring intensive care unit treatment or unable to walk after 3 months. Results obtained with the global activator phorbol myristate acetate, as well as with fMLF in TNF alpha-primed leukocytes, suggested that the deficiency of oxygen radical production in patients with severe GBS was the result of a specific deficiency of radical production in response to FPR/FPRL1 ligands rather than an inherent deficiency of NADPH oxidase function.
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