No abstract

We have developed an immunoadsorbent (IA) for ex vivo removal of IgE after in vitro screening of matrix (Sepharose and tresyl-activated Toyopearl) and ligand (monospecific rabbit polyclonal anti-IgE antiserum and monoclonal antibodies (Abs) or their Fab fragments). Specific adsorptive capacity (SAC) for IgE was maximal in Sepharose-based IA with both types of Abs. Fab-containing IA on Sepharose retained 70-90% of the SAC of native Ab-containing IA. Toyopearl-based IA showed comparable SAC under static conditions but worked unsatisfactorily under continuous flow conditions. To assess the complement-activating capacity (CAC) of IA in vitro anaphylatoxin (C3a, C4a, C5a) generation was applied. CAC was directly related with the amount of immobilized Ab ligand, without depending on Ab specific activity. Fab-containing IA showed more CAC than native Ab-containing IA, and polyclonal IA more than monoclonal IA. Therefore, IA for IgE apheresis were prepared from native monoclonal Abs and CNBr-activated Sepharose CL 4B under aseptic conditions and packed into a glass column. This IA was used in 17 clinical IgE apheresis treatments of five atopic asthma patients. No substantial side effects were observed; in vivo IA effectively removed IgE from plasma (83 to 98%).

Иммуновоспалительные (аутоиммунные) заболевания относятся к числу наиболее тяжелых хронических болезней человека, их частота в популяции приближается к 10%. Самые яркие представители это класса болезней -иммуно-воспалительные ревматические заболевания (ИВРЗ), пора-жающие взрослых и детей, в первую очередь ревматоидный артрит (РА), ювенильные артриты, спондилоартриты, вклю-чая псориатический артрит, системная красная волчанка

Background Predictors of response to biologic therapy in rheumatoid arthritis (RA) are needed to achieve a more individualized therapy. Seropositivity has been associated with better response to rituximab (RTX). Objectives To assess the 6-month response to the first RTX course in RA according to RF and ACPA status. Methods Ten European registries submitted anonymized datasets from RA patients who had started RTX, and datasets were pooled and analysed. Chi-square test for comparison of categorical variables and t-test for continuous data were used. Predictors of response were identified by logistic regression analysis. Results 3266 patients were included in the cohort. 79.9% of patients were RF (+) (2041 out of 2553) and 73.2% were ACPA (+) (877 out of 1198). 718 patients were double positive (DP) and 147 double negative (DN). 2200 patients were RF (+) and/or ACPA (+). Improvements of DAS28 (ΔDAS28) at 6 months were significantly better for RF (+) than RF (–) patients as well as for ACPA (+) than ACPA (–), DP vs. DN and RF and/or ACPA (+) vs. DN (table 1). A significantly higher percentage of ACPA (+) and DP patients achieved EULAR Good Response at 6 months compared to ACPA (–) and DN, respectively (table 1). The completeness of data was very similar for seropositive and seronegative patients, with the percentage of missing data at 6 months being approximately 50% in all groups. A significantly higher percentage of seronegative patients received retreatment by 6 months than seropositive patients. In univariate analyses adjusted for age and gender ACPA positivity (OR=2.03, p=0.016) and DP (OR=2.43, p=0.03) but not RF positivity (OR=1.53, p=0.07) predicted EULAR good response to therapy with RTX at 6 months after the first treatment. Table 1. Clinical outcomes at 6 months for RTX treated patients according to RF and ACPA status RF (+)RF (–)p-valueACPA (+)ACPA (–)p-value Baseline DAS285.85±1.365.63±1.340.001*5.8±1.355.68±1.32NS DeltaDAS28 6m1.94±1.51.65±1.340.0051.93±1.511.40±1.47<0.0001 EULAR Good/Moderate/No 6m21.5/62/16.5%17.4/63.4/19.2%0.0623.9/58.7/17.4%14.9/62.9/22.2%0.009 Remission 6m13.8%11.3%NS13.5%10.9%NS DPDNp-valueRF and/or ACPA (+)DNp-value Baseline DAS285.81±1.365.65±1.36NS5.84±1.355.65±1.36NS DeltaDAS28 6m1.95±1.541.41±1.510.0071.93±1.491.41±1.510.005 EULAR Good/Moderate/No 6m24.7/58.4/16.9%13.8/65/21.2%0.0621.4/61.9/16.7%13.8/65/21.2%0.038 Remission 6m13.9%12.5%NS13.7%12.5%NS *Corrected for baseline DAS28. Conclusions In this large observational cohort of RA patients treated with RTX, seropositive patients achieved significantly greater reductions in DAS28 at 6 months compared to seronegative patients. Baseline ACPA positivity may be a better predictor for good response to RTX than RF positivity. Disclosure of Interest None Declared

The administration of sildenafil substantially improves survival in patients with PAH associated with CTD as compared with the historical control. The identification of poor prognostic factors in this cohort of patients and early diagnosis will favor the personification of therapy for the fatal manifestation of CTD.