Differential responsiveness to immunoablative therapy in refractory rheumatoid arthritis is associated with level and avidity of anti-cyclic citrullinated protein autoantibodies: a case study

In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to 388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity.     

The inhibiting effect of a low-dose ionizing radiation on the primary humoral immunity in the early period of an postnatal ontogeny

The single exposition of 3- and 4-week mice in a dose 0.1 Gy resulted in depressing primary T-dependent humoral immune response. Unlike juvenile ones at adult 16-week animals the stimulation antibody-formation took place. As a result of the administration of immunomodulating drugs, thymogene and nucleinate of a sodium in irradiation mice of 3-week age was an augmentation of the number of antibody-producing cells relatively in 2 and 4 times. At the same time at irradiated in dose 0.1 Gy of adult mice thymogene abrogated the stimulating effect of radiation. It is suggested that the probable cause of the immunosuppressing effect of a small dose of radiation can be an inactivation of a radiosensitive subpopulation of helper cells or selective stimulation of the functional activity of neonatal suppressor cells.     

Polarized light based scheme to monitor column performance in a continuous foam fractionation column

Background  

A polarized light scattering technique was used to monitor the performance of a continuously operated foam fractionation process. The S ₁₁ and S ₁₂ parameters, elements of the light scattering matrix, combined together (S ₁₁ +S ₁₂) have been correlated with the bubble size and liquid content for the case of a freely draining foam. The performance of a foam fractionation column is known to have a strong dependence on the bubble size distribution and liquid hold up in foam. In this study the enrichment is used as a metric, representative of foam properties and column performance, and correlated to the S ₁₁ +S ₁₂ parameter.     

The detection of the herpes simplex virus 1 and 2 antigens in clinical specimens by using monoclonal antibodies

The possibility of using monoclonal antibodies (McAb), obtained earlier, for the detection of herpes simplex virus (HSV) in clinical specimens taken from sick and infected persons was studied. The examination of 90 persons revealed that the mixture of McAb 4A and 2C could effectively detect the presence of HSV antigen in the indirect immunofluorescence assay (IFA) directly in cells contained in cytological preparations (smears, scrapes, impressions) obtained from different organs of patients. The search of optimum combinations of McAb for the detection of HSV antigens by the method of the solid-phase enzyme immunoassay (EIA) was carried out. This study, made on purified HSV used as an experimental model, revealed that the maximum sensitivity could be achieved with the use of two McAb (4f6 and 7c4) out of three McAb (4f6, 7c4 and 3d10). The approbation of both variants of EIA on clinical specimens taken from 99 patients (blood clots, seminal fluid, scrapes of cervical canal cells, peripheral blood lymphocytes) showed that the addition of McAb 3d10 made it possible to detect 8 more positive specimens. 754 specimens from 337 patients were studied with the use of McAb-based EIA, and in 204 of these patients (61%) HSV antigen was detected. The results obtained with the use of our McAb were compared with the data obtained with certified commercial test systems. The coincidence of the EIA data with those obtained with the use of the Murex Wellcozyme HSV test system (UK) was registered in 75% of cases (in 15 out of 20 cases). The coincidence of the IFA data with those obtained with the use of the Sanofi test system (France) was observed in all 19 cases (100%).     

Recognition of emotions based on facial expressions in subjects with different personality traits

A reaction time and accuracy of visual recognition of emotions of joy, anger and fear in their relation to personality traits was studied in 68 healthy subjects. According to scores of Kettell Questionnaire all the participants were divided into two groups: emotionally unstable and emotionally stable, which differed in their emotional and communication traits. It was shown that in the stable group recognition of fear was significantly worse and more slowly than in the unstable group. Besides, the emotionally stable subjects recognized the frightened facial expression less accurate and slowly than they did the joyous and threatening ones. The reaction time and recognition level was found to be closely correlated with some personality traits. These traits were different in two groups and differed from data in the control session of gender recognition. The conjunction between recognition of fearful facial expression and the personality traites and its adaptive significance were discussed. The data seems to be essential for understanding of individual strategy of communication.     

Identification of Catalytically Active Groups in Inulinase from Bacillus polymyxa 722

Inulinase from Bacillus polymyxa 722, hydrolyzing a polyfructosan inulin, was studied. The dependence of inulinase activity on pH, measurements of pK value, calculation of the ionization heat, photoinactivation with methylene blue, and inhibition with p-chloromercuribenzoate suggest that the active center of this enzyme contains imidazole and sulfhydryl groups. A possible mechanism underlying the cleavage of -2,1-fructoside bonds in the inulin molecule by inulinase is considered.