Antibody response against gastrointestinal antigens in demyelinating diseases of the central nervous system.

BACKGROUND: Antibodies against gastrointestinal antigens may indicate altered microbiota and immune responses in the gut. Recent experimental data suggest a connection between gastrointestinal immune responses and CNS autoimmunity. METHODS: Antibodies against gliadin, tissue transglutaminase (tTG), intrinsic factor (IF), parietal cells (PC) and Saccharomyces cerevisiae (ASCA) were screened in the sera of 45 patients with AQP4-seropositive neuromyelitis optica (NMO) and NMO spectrum diseases (NMO/NMO-SD), 17 patients with AQP4-seronegative NMO, 85 patients with clinically definite multiple sclerosis (MS), and 48 healthy controls (HC). RESULTS: Thirty-seven percentages of patients with AQP4-seropositive NMO/NMO-SD and 28% of patients with MS had at least one particular antibody in contrast to 8% of HC (P < 0.01, respectively). Antibodies were most common (46%) in AQP4-seropositive myelitis (P = 0.01 versus HS, P = 0.05 versus MS). Anti-gliadin and ASCA were more frequent in the AQP4-seropositive NMO-spectrum compared to controls (P = 0.01 and P < 0.05, respectively). CONCLUSION: Antibody responses against gastrointestinal antigens are common in MS and AQP4-seropositive NMO/NMO-SD, especially in longitudinally extensive myelitis.

Social cognition and Theory of Mind in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Theory of Mind (ToM) is an ability to understand and interpret another person's beliefs, emotions, and intentions. ToM requires both cognitive and emotional perspective taking and is deficient in several neuropsychiatric disorders all connected with impaired social functioning. Cognitive and mood dysfunctions have been recognized as common symptoms in multiple sclerosis (MS). METHODS: We investigated social cognition in 40 ambulatory patients with MS compared to 35 healthy controls by using verbal and non-verbal ToM tests (Faux Pas, Baron-Cohen's Adult Eyes and Faces test) and Baron-Cohen's Empathy questionnaire. The effect of disability and disease duration on social cognition was also analyzed by multiple logistic regression analysis after adjusting for confounding factors of age, gender, intelligence, depression, and anxiety. RESULTS: Even when adjusted, patients with MS made significantly more mistakes in non-verbal test (adult Eyes Test), and more disabled patients performed worse in both verbal and non-verbal ToM tests (Eyes Test and Faux Pas) compared to controls. Patients with a shorter disease course described themselves as more empathetic. DISCUSSION: In the absence of marked cognitive decline and disability, patients with ambulatory MS had a deficit interpreting social situations and performing in interpersonal contexts.

Immunological effects of an arginine side chain contaminating synthetically prepared peptides.

The side chain, 4-methoxy-2,3,6-trimethylbenzenesulphonyl (Mtr), is a protective group coupled to arginine to mask the omega-nitrogen, in order to protect the guanidino function during peptide synthesis by the 9-fluorenylmethoxycarbonyl (Fmoc) procedure (Walker, 1994). This group is removed at the completion of peptide synthesis; however, the cleavage process can be incomplete. We have found that animals injected with a mixed population of pure, i.e. unmodified, and Mtr-containing MBP peptides have an immunodominant humoral response to the Mtr-bearing peptide. This response is dependent on the characteristics of the MBP peptide involved. For two MBP peptides, the Mtr-containing peptide had increased binding to antibody over pure peptide. For two other peptides, only the Mtr-containing peptide bound antibody while the unmodified peptide did not. In a separate system involving a polyclonal response to an unrelated peptide from beta2-microglobulin (beta2 m), the dominance of the Mtr group was also evident. These results provide further evidence that a small side chain on a single amino acid in a peptide can markedly alter the immunogenicity and antigenicity of that peptide for antibody reactivity. This evidence emphasizes the need for a critical awareness of each component of peptide synthesis and its potential to alter the immunoreactivity of the final product.

Cerebrospinal fluid (CSF) investigations in migraine.

A normal cell count as well as normal CSF pressure levels were found in both classic and common migraine patients during and between attacks. Total protein content was significantly lower in the migraine patients than in the controls, but no changes were found in the CSF protein fractions. The CSF 5-hydroxyindoleacetic acid level of the migraine patients proved to be higher than in the controls, whereas the homovanillic acid concentration was within the control limits.

Perforant path activation of the hippocampus: spatial distribution, effects of urethane and atropine.

Spatial distribution of field responses evoked by perforant path stimulation were studied in the hippocampus of both anaesthetized and drug-free rats. Simultaneous recordings with an array of 4 electrodes allowed us to construct a 2-dimensional map of the evoked field potentials. In addition, we examined the effects of atropine-SO4 and urethane on the amplitude of the dentate response. Trisynaptic activation of the CA1 region occurred regularly in the drug-free rat while CA1 population spikes were rarely seen in the anaesthetized animal. The latency of the CA1 population spike was shortest at the fimbrial side and increased gradually towards the subicular side. In the dentate gyrus atropine increased the amplitude of the population spike. We suggest that atropine may interfere with the septo-hippocampal feed-forward inhibition, and urethane may decrease the effectiveness of the perforant path-granule cell synapse, as well as the intrahippocampal excitatory circuit.

Spatial mapping, working memory, and the fimbria-fornix system.

Rats with lesions severing either the subcallosal fornix (Fo) or the medial half of the fimbria (Fi) were used. They were compared with control (Co) animals in a working memory task (serial alternation) and a reference memory task (cue-guided alternation). Neither task required spatial mapping strategy. Damaging the Fi, but not the Fo, caused a severe deficit in the serial alternation task. Analysis of individual performance revealed that Fi rats either adopted a "side strategy, " resulting in worse than chance performance. This active perseveration required intact working memory mechanism. In the cue-guided alternation task, Fo animals proved superior to Co and Fi rats. These findings are inconsistent with notions that the exclusive role of the hippocampus is spatial mapping or storing of recent memories. They indicate also differential involvement of the fimbria and fornix fibers in behavior.