Localization of self antigen: implications for antigen presentation and induction of tolerance

The fifth component of complement (C5) is a self antigen expressed in serum of normal mice at a concentration of about 50 μg/ml. We have previously shown that C5 is constitutively processed and presented by antigen-presenting cells (APC) in normal mice to induce and maintain complete tolerance in major histocompatibility complex (MHC) class II-restricted T cells. This report addresses the question of whether C5 presentation involves exogenous antigen which has been internalized for processing or whether intracellular, biosynthesized C5 is being presented with MHC class II. Macrophages were found to synthesize, but not secrete C5 in bone marrow chimeras made from irradiated C5-deficient [C5(?)] hosts reconstituted with C5-sufficient [C5(+)] bone marrow [C5(+) ← C5(?)]. In these mice, macrophages are the only source of C5. [C5(+) ← C5(?)] chimeras are not tolerant of C5 and generate C5-specific T and B cell responses upon immunization indistinguishable from those of C5(-) mice. Macrophages from [C5(+) ← C5(-)] chimeras are unable to activate C5-specific T cell hybrids in vitro unlike macrophages from a C5(?) strain that has matured in a C5-expressing environment [C5(?) ← C5(+) chimeras]. This shows that under physiological conditions in vivo intracellular C5 does not get access to the class II presentation pathway and thus, does not induce tolerance in class II-restricted T cells.     

Electroconvulsive therapy in Parkinson's syndrome with “on-off” phenomenon

Summary During long-term treatment with L-dopa in Parkinson's syndrome on-off phenomenon develops in many cases, often entailing considerable therapeutic problems. Decreased sensitivity in postsynaptic striatal dopamine (DA) receptors has been shown to occur in parkinsonian patients during long-term treatment with L-dopa. This has been suggested as one possible mechanism for development of the on-off phenomenon. In contrast to L-dopa treatment electroconvulsions have been shown to increase sensitivity in the DA receptors, when administered to animals.The antiparkinsonian effect of electroconvulsive therapy (ECT) was investigated in five parkinsonian patients with on-off phenomenon, with or without concomitant signs of mental depression. ECT was administered according to praxis in treatment of mental depression. Drug therapy, including L-dopa, was maintained on previously adjusted doses during and after ECT.A marked improvement in the parkinsonian symptoms as well as in the on-off phenomenon occurred in three of the patients, persisting for several months. The other two patients showed only slight and transient improvement.It thus seems that ECT may be useful as a supplementary treatment in parkinsonian patients with on-off phenomenon. The antiparkinsonian effect of ECT is probably mediated by increased sensitivity in postsynaptic DA structures.     

Lessons from studies of antigen-specific T cell responses in Multiple Sclerosis

Multiple Sclerosis (MS) is considered a T cell-mediated autoimmune disease of central nervous system myelin. Based on elegant experiments in an animal model of MS, experimental allergic encephalomyelitis (EAE), a number of myelin proteins and peptides derived from these can induce inflammatory demyelinating lesions. Recent studies with transgenic mice expressing human HLA-DR molecules and a myelin basic protein (MBP)-specific T cell receptor as well as data from a phase II clinical trial with an altered peptide ligand based on MBP peptide (83-99) provide convincing evidence that the pathogenetic concepts which largely stem from the above EAE studies are valid in MS, too.     

Síndrome antissintetase: anti-PL-7, anti-PL-12 e anti-EJ

ObjectivesDue to the scarcity of studies in the literature, we conducted an analysis of a series of patients with the anti-PL-7, PL-12 and EJ types of antisynthetase syndrome (ASS).MethodsWe conducted a retrospective cohort study of 20 patients with ASS (8 with anti- PL-7, 6 with PL-12, 6 with EJ) monitored in our department between 1982 and 2012.ResultsThe mean patient age at disease onset was 38.5 ± 12.9 years, and the disease duration was 4.5 ± 6.4 years. Of all the patients, 70% were white and 85% were female. Constitutional symptoms occurred in 90% of cases. All patients presented objective muscle weakness in the limbs; in addition, 30% were bedridden and 65% demonstrated high dysphagia at diagnosis. Joint and pulmonary involvement and Raynaud's phenomenon occurred in 50%, 40% and 65% of cases, respectively, with more than half of the patients presenting incipient pneumopathy, ground-glass opacity and/or pulmonary fibrosis. There were no cases of neurological and/or cardiac involvement. All patients received prednisone or other immunosuppressants depending on tolerance, side effects and/or disease refractoriness. Importantly, patients with the anti-EJ type of ASS demonstrated higher rates of recurrence. Two patients died during follow-up, and 1 patient had breast cancer at the time of diagnosis.ConclusionsASS (anti-PL-7, PL-12 and EJ) was found to predominantly affect white women. Although the autoantibodies described in the present study are more related to pulmonary than joint involvement, our patients showed a significant percentage of both types of involvement and a high percentage of myopathy. We also observed a low mortality rate.     

Fibromyalgia and chronic widespread pain in patients with inflammatory bowel disease: a cross sectional population survey

OBJECTIVE: To assess the prevalence of fibromyalgia (FM) and chronic widespread pain (CWP) in a population based cohort of patients with inflammatory bowel disease (IBD). METHODS: Patients in a prospective survey on newly diagnosed IBD were, 5 years after study entry, invited to a clinical examination including the investigation of musculoskeletal manifestations. A total of 521 patients were examined, corresponding to 80% of surviving cases with definite diagnoses of ulcerative colitis (UC) and Crohn's disease (CD). The diagnoses of FM and CWP strictly followed the American College of Rheumatology classification criteria of 1990. RESULTS: At clinical examination, FM was diagnosed in 18 patients (3.5%), 3.7% with UC and 3.0% with CD. The prevalence was 6.4% in females and 0.4% in males. Thirty-eight patients (7.3%) had CWP (8.5% with UC; 4.8% with CD). The female:male ratio was 27:3 in the UC group and 8:0 in CD. In 19 patients (50%), CWP occurred after onset of IBD. No correlation with the extent of intestinal inflammation and the occurrence of FM and CWP was found. CONCLUSION: The prevalences of FM and CWP in patients with IBD were similar to those of the general population. There were no differences in prevalence of FM and CWP between UC and CD. Chronic idiopathic inflammation of the intestine does not appear to predispose to chronic widespread pain.     

Prevalence of ankylosing spondylitis in males and females in a young middle-aged population of Troms?, northern Norway.

In an epidemiological survey in Tromsø, northern Norway a prevalence of definite ankylosing spondylitis (AS) of between 1.1% and 1.4% was found (males: 1.9-2.2% and females: 0.3-0.6%). The ratio of male to female was between 3.9 and 6.1 in favour of the male sex. It was calculated that 6.7% of the B27 positive individuals had AS, and that 22.5% of the B27 positive subjects with back pain or stiffness suffered from AS.