SummaryParoxysmal nocturnal haemoglobinuria (PNH) clones are frequently detected in patients with aplastic anaemia (AA). To evaluate the prognostic role of PNH clone presence we conducted a prospective study in 125 AA patients treated with combined immunosuppressive therapy (IST). Seventyfour patients (59%) had a PNH clone (PNH+ patients) at diagnosis, with a median clone size of 0Á60% in granulocytes and 0Á15% in red blood cells. The response rate at 6 months was higher in PNH+ patients than that in PNH-patients, both after first-and second-line IST: 68% vs. 45%, P = 0Á0164 and 53% vs. 13%, P = 0Á0502 respectively. Moreover, 42% of PNH+ patients achieved complete remission compared with only 16% of PNH-patients (P = 0Á0029). In multivariate logistic regression analysis, PNH clone presence (odds ratio 2Á56, P = 0Á0180) and baseline absolute reticulocyte count (ARC) ≥30 9 10 9 /l (odds ratio 5Á19, P = 0Á0011) were independent predictors of response to treatment. Stratification according to PNH positivity and ARC ≥30 9 10 9 /l showed significant distinctions for cumulative incidence of response, overall and failure-free survival. The results of this prospective study confirmed the favourable prognostic value of PNH clone presence in the setting of IST for AA.

BackgroundEarly diagnosis of rheumatoid arthritis (RA) is crucial to providing effective therapy and often hampered by unspecific clinical manifestations. Elevated levels of extracellular circulating DNA (cirDNA) in patients with autoimmune disease were found to be associated with etiopathogenesis. To our knowledge, this is the first study to investigate the putative diagnostic use of cirDNA in RA and its association with disease activity.MethodsBlood samples were taken from 63 healthy subjects (HS) and 74 patients with RA. cirDNA was extracted from plasma and cell surface-bound cirDNA fractions (csbDNA). cirDNA concentration was measured by quantitative real-time polymerase chain reaction. Rheumatoid factor was analyzed by immunonephelometry, whereas C-reactive protein and anticitrullinated protein/peptide antibodies (ACPA) were detected by enzyme-linked immunosorbent assay.ResultsPlasma cirDNA was significantly elevated in patients with RA compared with HS (12.0 versus 8.4 ng/ml, p < 0.01). In contrast, nuclear csbDNA (n-csbDNA) was significantly decreased (24.0 versus 50.8 ng/ml, p < 0.01), whereas mitochondrial csbDNA (m-csbDNA) was elevated (1.44 × 106 copies/ml versus 0.58 × 106 copies/ml, p < 0.05) in RA. The combination of csbDNA (mitochondrial + nuclear) with ACPA reveals the best positive/negative likelihood ratios (LRs) for the discrimination RA from HS (LR+ 61.00, LR− 0.03) in contrast to ACPA (LR+ 9.00, LR− 0.19) or csbDNA (LR+ 8.00, LR− 0.18) alone.ConclusionsNuclear and mitochondrial cirDNA levels in plasma and on the surface of blood cells are modulated in RA. Combination of cirDNA values with ACPA can improve the serological diagnosis of RA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1295-z) contains supplementary material, which is available to authorized users.

Treatment of the 3-diphenylphosphorylbenzoic acid amides 3a,b with the Lawesson reagent resulted in 3-diphenylthiophosphorylbenzoic acid thioamides 4a,b, which easily underwent cyclopalladation at the C-2 position of the central benzene ring to give new hybrid pincer complexes 5a,b with κ 3 -SCS coordination. Molecular structures of the complexes were characterized by X-ray diffraction. The peculiarities of chemical bonding in 5a were investigated via topological analysis of charge density in the crystal. The palladium complexes 5a,b demonstrated high catalytic activity for the Suzuki cross-coupling reactions of aryl bromides with phenylboronic acid and exhibited luminescence at 77 and 300 K.