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Background: Multiple sclerosis (MS) is associated with high prevalence of cognitive impairment, ranging from 40 to 80%. The purpose of this single-center retrospective study was to examine the relation between cognitive function, as measured by Symbol Digit Modalities Test (SDMT), with fatigue, anxiety, and depression symptoms in a Belgian cohort of patients with MS. Methods: Sociodemographic and clinical data were analyzed in 66 (F:40, M:26) Belgian patients with a diagnosis of MS. The cognitive function was assessed with the oral version of SDMT, depression and anxiety symptoms with the Hospital Anxiety and Depression scale (HAD), fatigue symptoms with the French valid version of the Fatigue Impact Scale in MS (EMIF-SEP), which is a scale composed of four dimensions (cognitive, physical, social, and psychological) allowing a multidimensional evaluation of fatigue. Results: The multivariate linear regression analysis demonstrated that lower SDMT scores were associated with higher EDSS score and psychological dimension of fatigue symptoms. No association were found between SDMT and anxiety or depression symptoms. Conversely, higher depression and anxiety symptoms were associated with higher total fatigue symptoms, but lower physical dimension of fatigue symptoms. Higher anxiety symptoms were also independently associated with higher social dimension of fatigue symptoms. Conclusion: A complex relationship exists between cognitive performance, fatigue, and neuropsychiatric symptoms in Belgian people with MS. The level of disability and fatigue adversely affects the cognitive function in MS, whereas depression and anxiety seem to not have a significant effect. A more complex relationship exists between fatigue and neuropsychiatric symptoms, with a divergent interplay between the different dimensions of fatigue that supports the multidimensional approach to assessing fatigue in MS.

•Early lymphopenia is a known side effect of dimethyl fumarate. However, it can be also late and/or recurrent.•Dimethyl fumarate has a long-term impact on lymphocyte biology, even after its discontinuation, with sustained absolute or relative reduction in CD8+ T cells.•The sustained reduction in CD8+ T cells may increase opportunistic infection risk.•The long-term effects of dimethyl fumarate should be taken in consideration when switching therapies.

Self-assembled monolayers (SAMs) on gold exposing α-d-Galp-(1→4)-β-d-Galp-(1→4)-β-d-Glcp (globotriose) are described. A synthetic pathway for the preparation of the bioactive carbohydrate globotriose coupled directly to bis(16-hydroxyhexadecanyl) disulfide ((HOC16H32S)2), as well as via tetra- or di(ethylene glycol) spacers, was developed. The SAMs were characterized by ellipsometry, contact angle goniometry, infrared reflection−absorption spectroscopy, and by their interactions with monoclonal antibodies. The ellipsometry measurements of mixed SAMs revealed thicknesses between 22 and 40 Å, depending on the ratio between carbohydrate and non-carbohydrate disulfides in the preparation solution. When the solution contained 10% or more of the carbohydrate adsorbate, the modified gold substrates displayed total wetting. Infrared reflection−absorption spectroscopy conferred well-ordered SAMs with a high degree of crystallinity. Furthermore, two monoclonal antibodies (IgM, MAHI 419 and IgG, MAHI 5) showed different affinity for mixed SAMs depending on the fraction and the structure of the carbohydrate component used (globotriose or globotriose tetra(ethylene glycol)), with the largest amount of protein bound for MAHI 419 at 1−10% of surface carbohydrate. These results demonstrate the usefulness of the SAM approach to explore molecular details such as the effect of a spacer or antigen distribution on antibody interactions at interfaces.

Mouse monoclonal antibodies (MAbs) DP8 [immunoglobulin G1(kappa)] and DH24 [immunoglobulin M(kappa)], which are specific for Haemophilus ducreyi lipopolysaccharide (LPS), were generated by fusing mouse myeloma NS0 cells with spleen cells of BALB/c mice immunized with a total membrane preparation of H. ducreyi. MAb DP8 reacted in whole-cell enzyme immunoassay (EIA) and colony dot immunoblotting with all 50 strains of H. ducreyi but not with any other bacteria tested, which suggests an exposed and species-specific epitope on the H. ducreyi cell surface. This conclusion was supported by the finding that DP8 bound to all six H. ducreyi LPSs tested but not to any of the Haemophilus influenzae or enterobacterial LPSs or synthetic glycoconjugates. The MAb DH24 bound to 43 of 50 strains of H. ducreyi and to few strains of H. influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis, as evaluated by whole-cell EIA and colony dot immunoblotting. The MAb DH24 reacted with five of the six H. ducreyi LPSs tested and with the lacto-N-neotetraose (Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4Glc) series of synthetic glycoconjugates, as determined by EIA. By using polysaccharides obtained after both mild acidic hydrolysis and strong alkali treatment and dephosphorylated samples as inhibitors of the MAbs binding to H. ducreyi LPS antigens, it could be shown that phosphate groups were essential for the binding of DP8 to LPS but that they did not affect antigenic recognition by DH24. None of the MAbs bound to isolated lipid A, but aggregation caused by the fatty acids of lipid A was essential for epitope recognition.

A murine monoclonal antibody, MAHI 3 (immunoglobulin G2b), that is broadly reactive with Haemophilus influenzae lipopolysaccharides (LPSs) but nonreactive with all enterobacterial LPSs tested was generated by fusing mouse myeloma cells with spleen cells of BALB/c mice immunized with azide-killed H. influenzae RM.7004. MAHI 3 bound to all H. influenzae, all other human Haemophilus spp., all Bordetella pertussis and Bordetella parapertussis, and all Aeromonas spp. tested but not to any Neisseria or Moraxella catarrhalis strains, as determined by enzyme immunoassay, colony dot immunoblotting, and immunoblotting. In an inhibition enzyme immunoassay, MAHI 3 reacted with all 45 H. influenzae LPSs tested but not with the LPS from the rough mutant I69 Rd-/b+, which has only 3-deoxy-D-manno-octulosonic acid (P) [Kdo(P)] and lipid A. The antibody was not inhibited by H. influenzae lipid A or lipid-free polysaccharide isolated after mild acid hydrolysis. Only native LPSs show positive inhibitory activity, indicating that part of lipid A is involved in the binding of MAHI 3. From the results, it is indicated that the structural element recognized by MAHI 3 is Hep alpha 1-->2Hep alpha 1-->3Hep alpha 1-->Kdo together with part of lipid A, including the phosphate.

Mouse monoclonal antibodies (MAbs) DP8 [immunoglobulin G1(kappa)] and DH24 [immunoglobulin M(kappa)], which are specific for Haemophilus ducreyi lipopolysaccharide (LPS), were generated by fusing mouse myeloma NS0 cells with spleen cells of BALB/c mice immunized with a total membrane preparation of H. ducreyi. MAb DP8 reacted in whole-cell enzyme immunoassay (EIA) and colony dot immunoblotting with all 50 strains of H. ducreyi but not with any other bacteria tested, which suggests an exposed and species-specific epitope on the H. ducreyi cell surface. This conclusion was supported by the finding that DP8 bound to all six H. ducreyi LPSs tested but not to any of the Haemophilus influenzae or enterobacterial LPSs or synthetic glycoconjugates. The MAb DH24 bound to 43 of 50 strains of H. ducreyi and to few strains of H. influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis, as evaluated by whole-cell EIA and colony dot immunoblotting. The MAb DH24 reacted with five of the six H. ducreyi LPSs tested and with the lacto-N-neotetraose (Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4Glc) series of synthetic glycoconjugates, as determined by EIA. By using polysaccharides obtained after both mild acidic hydrolysis and strong alkali treatment and dephosphorylated samples as inhibitors of the MAbs binding to H. ducreyi LPS antigens, it could be shown that phosphate groups were essential for the binding of DP8 to LPS but that they did not affect antigenic recognition by DH24. None of the MAbs bound to isolated lipid A, but aggregation caused by the fatty acids of lipid A was essential for epitope recognition.

A murine monoclonal antibody, MAHI 3 (immunoglobulin G2b), that is broadly reactive with Haemophilus influenzae lipopolysaccharides (LPSs) but nonreactive with all enterobacterial LPSs tested was generated by fusing mouse myeloma cells with spleen cells of BALB/c mice immunized with azide-killed H. influenzae RM.7004. MAHI 3 bound to all H. influenzae, all other human Haemophilus spp., all Bordetella pertussis and Bordetella parapertussis, and all Aeromonas spp. tested but not to any Neisseria or Moraxella catarrhalis strains, as determined by enzyme immunoassay, colony dot immunoblotting, and immunoblotting. In an inhibition enzyme immunoassay, MAHI 3 reacted with all 45 H. influenzae LPSs tested but not with the LPS from the rough mutant I69 Rd-/b+, which has only 3-deoxy-D-manno-octulosonic acid (P) [Kdo(P)] and lipid A. The antibody was not inhibited by H. influenzae lipid A or lipid-free polysaccharide isolated after mild acid hydrolysis. Only native LPSs show positive inhibitory activity, indicating that part of lipid A is involved in the binding of MAHI 3. From the results, it is indicated that the structural element recognized by MAHI 3 is Hep alpha 1-->2Hep alpha 1-->3Hep alpha 1-->Kdo together with part of lipid A, including the phosphate.

Monoclonal antibodies against the lipooligosaccharide ofHaemophilus ducreyi were produced. Two of them, MAHD6 and MAHD7, were found to be relatively, although not absolutely, specific and reacted with nearly all strains ofHaemophilus ducreyi tested: 59 of 60 and 60 of 60, respectively. The diagnostic usefulness of MAHD7 was assessed. Clinical specimens collected in Zambia from patients with genital ulcers were tested using indirect immunofluorescence (IF), enzyme immunoassay (EIA), the polymerase chain reaction (PCR) and bacterial culture. Compared with culture, IF had a sensitivity of 100 %; compared with PCR, sensitivity was 89 %. The corresponding figures for the EIA were 83 % and 74 %, respectively. The sensitivity of culture compared with PCR was 63 %. The results suggest that IF on genital smears using M AH D7 might be an excellent tool for the diagnosis of chancroid in high-prevalence populations. However, further evaluation of the specificity of this test is needed.

•Cognitive dysfunction is a common feature in MS.•Diagnosing cognitive dysfunction due to an accompanying neurodegenerative dementia represents a challenge.•AD biomarkers may be helpful in selected MS patients with severe, cortical type, cognitive dysfunction.