Combined manual and automated immunophenotypisation identified disease-specific peripheral blood immune subpopulations in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis.

Objectives: Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are associated with abnormal immune cell functions. We combined manual and automated profiling in subpopulations of T-cells, B-cells and monocytes, in parallel to functional testing and clinical correlation.

Methods: Using flow cytometry, we analysed the expression of CCR4, CCR6 and CXCR5 on helper and cyotoxic T-cells, CD32B and CD86 on naïve and memory B-cells, and CCR1, CCR2, CCR4 and CXCR4 on monocytes in chronic high-disease activity patients to identify peripheral blood subpopulations.

Crenolanib is a type I tyrosine kinase inhibitor that inhibits mutant D816 isoforms prevalent in systemic mastocytosis and core binding factor leukemia.

Activating D816 mutations of the class III receptor tyrosine kinase are associated with the majority of patients with systemic mastocytosis (SM), but also core binding factor (CBF) AML, making mutations attractive therapeutic targets for the treatment of these cancers. Crenolanib is a potent and selective inhibitor of wild-type as well as mutant isoforms of the class III receptor tyrosine kinases FLT3 and PDGFRα/β. Notably, crenolanib inhibits constitutively active mutant-FLT3 isoforms resulting from amino acid substitutions of aspartic acid at codon 835, which is homologous to codon 816 in the gene - suggesting sensitivity against mutant-KIT D816 isoforms as well.

The G protein-coupled receptor CysLT1 mediates chemokine-like effects and prolongs survival in chronic lymphocytic leukemia.

The G protein-coupled receptor (GPCR) CXCR4 is involved in bone marrow tropism and survival of chronic lymphocytic leukemia (CLL) cells. The function of the GPCRs cysteinyl leukotriene receptor 1 (CysLT1) and CysLT2 remains elusive. Here we demonstrate that in CLL and normal B lymphocytes, CysLT1 mRNA is consistently expressed, in contrast to low CysLT2 levels.

Small and large bowel manifestation of leukocytoclastic vasculitis.

Leukocytoclastic vasculitis is a disease mostly limited to the skin. Extracutaneous manifestations that include visceral involvement are normally self-limiting and not life-threatening. We describe a 44-year-old man with palpable purpura, polyarthritis and microhematuria who developed severe vasculitis of the small and large bowel.