AbstractThree weeks after the administration of intravenous methylprednisolone therapy, a 42-year-old female patient suffering from relapsing-remitting multiple sclerosis (RR-MS) presented with a profound elevation of liver transaminases (GOT 485 U/l, GPT 1082 U/l, glutamyl transpeptidase 170 U/l). Liver biopsy revealed a profound, still active hepatitis with portal lymphocytic infiltration and fibrosis. Most likely, existing acute hepatitis was of autoimmune origin and emerged from an immune rebound phenomenon after immunosuppressive therapy.

Objective: Members of the tumor necrosis factor (TNF) receptor superfamily play a major role in the pathogenesis of multiple sclerosis. To elucidate the role of TNF receptors, in 53 relapsing-remitting multiple sclerosis patients, we measured the TNF receptor 1 and receptor 2 (TNF-R1 and TNF-R2) mRNA levels in peripheral blood leukocytes in natural history (n = 27) and during administration of interferon (IFN) β-1a (n = 26). Methods: Every 3 months for the duration of 1 year peripheral blood leukocytes were investigated by quantitative reverse transcription polymerase chain reaction. Every 6 months, MRI scans of the brain were analyzed semiquantitatively. Results: At baseline, clinical expanded disability status scale score and TNF-R1 mRNA level were correlated. In the therapy group, the difference between T2 lesion load at baseline and after 12 months correlated negatively with the difference between TNF-R1 mRNA level at baseline and after 12 months. Subcutaneously applied IFN β increased the amount of TNF-R1 mRNA, but partly decreased the amount of TNF-R2 mRNA in clinically and subclinically defined responders to therapy after 1 year compared to baseline. Conclusion: This result might support the notion that due to different signal transduction properties of both receptors in the natural course of multiple sclerosis, TNF-α signaling in leukocytes via TNF-R1 might be beneficial, but detrimental via proinflammatory TNF-R2: part of the therapeutic efficacy of current first-line standard therapy with IFN might be due to the modulation of signal transduction pathways.

No abstract

No abstract

No abstract

No abstract

No abstract

Background La/SSB is a phosphoprotein that associates with various small RNA molecules. It has been found that the primary phosphorylation site of the molecule during various physiological processes is in Ser366. Objectives To determine whether the phosphorylation state of Ser366 could affect the antigenicity and the recognition of the protein by antibodies from patients with primary Sjögren's syndrome (pSS). Methods Peptides 349-368aa and phos349-368aa (with the Ser366 residue phosphorylated) were synthesized. Sera with anti-La specificity from 30 patients with pSS and sera from 19 normal individuals were examined against the two synthetic peptides in ELISA. The antibody specificity against the epitopes was tested with homologous and heterologous inhibition assays. Results Of pSS sera 23% reacted against the 349-368aa peptide. Sera binding to unphosphorylated peptide reacted also with phos349-368aa. Although the same sera gave a positive reaction against both peptides, the optical density values received from antibodies to phos349-368aa were higher, indicating a higher concentration or stronger affinity. When phos349-368aa was used as soluble inhibitor, in homologous inhibition the reactivity was almost completely abolished (92%). In contrast, when the unphosphorylated peptide was used as inhibitor, the reactivity of sera against phos349-368aa was only partially reduced (35%), indicating that sera from these patients possess two distinct groups of antibodies: one against the unphosphorylated and one against the phosphorylated epitope. Conclusion The phosphorylation of the serine366 residue resulted in a significant increase in antibody binding on epitope 349-368aa of La/SSB. These observations might explain the increased antigenicity of La/SSB autoantigen in various pathological situations in which phosphorylation may occur. 2 Surface-bound immune complexes containing antibodies to collagen type II induce production of TNF-α α, IL-1β β and IL-8 from monocytes via Fcγ γRII