Could the IgA isotype provide additional information in systemic sclerosis patients? A retrospective study entailing IgA isotyping in a Mediterranean systemic sclerosis cohort.

Objectives: Anti-CENP-B (ACA), anti-topoisomerase I (ATA) and anti-RNA polymerase III (RP3) autoantibodies are included in the 2013 SSc-ACR/EULAR classification criteria. The detection of additional autoantibodies is of interest when those are negative. Additionally, we wonder if the IgA isotype might play a role in SSc.

Determination of Autoantibody Isotypes Increases the Sensitivity of Serodiagnostics in Rheumatoid Arthritis.

Anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are the most commonly used diagnostic markers of rheumatoid arthritis (RA). These antibodies are predominantly of the immunoglobulin (Ig) M (RF) or IgG (ACPA) isotype. Other subtypes of both antibodies-particularly IgA isotypes and other autoantibodies-such as RA33 antibodies-have been repeatedly reported but their diagnostic value has still not been fully elucidated.

Notch-signalling is required for head regeneration and tentacle patterning in Hydra.

Local self-activation and long ranging inhibition provide a mechanism for setting up organising regions as signalling centres for the development of structures in the surrounding tissue. The adult hydra hypostome functions as head organiser. After hydra head removal it is newly formed and complete heads can be regenerated.

E-64c-hydrazide: a lead structure for the development of irreversible cathepsin C inhibitors.

Cathepsin C is a papain-like cysteine protease with dipeptidyl aminopeptidase activity that is thought to activate various granule-associated serine proteases. Its exopeptidase activity is structurally explained by the so-called exclusion domain, which blocks the active-site cleft beyond the S2 site and, with its Asp 1 residue, provides an anchoring point for the N terminus of peptide and protein substrates. Here, the hydrazide of (2S,3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane (E-64c) (k2/Ki =140±5 M(-1)  s(-1)) is demonstrated to be a lead structure for the development of irreversible cathepsin C inhibitors.

High-affinity cyclic peptide matriptase inhibitors.

Background: Sunflower trypsin inhibitor-1 (SFTI-1) and Momordica cochinchinensis trypsin inhibitor-II (MCoTI-II) are potent protease inhibitors comprising a cyclic backbone.

Results: Elucidation of structure-activity relationships for SFTI-1 and MCoTI-II was used to design inhibitors with enhanced inhibitory activity.

Conclusion: An analog of MCoTI-II is one of the most potent inhibitors of matriptase.