In vitro studies on the Fc-receptor function of mononuclear phagocytes in rheumatoid arthritis: relation between the Fc-receptor blockade and the concanavalin A-binding capacity of autologous immunoglobulin G

in Journal of Clinical Immunology (1986), 6(6), 442-456

The Fc-receptor (Fc-R) function of monocytes isolated from 19 control subjects and from 30 patients presenting with a rheumatoid arthritis (RA) was assessed in vitro by a classical rosette assay using IgG ... [more ▼]

The Fc-receptor (Fc-R) function of monocytes isolated from 19 control subjects and from 30 patients presenting with a rheumatoid arthritis (RA) was assessed in vitro by a classical rosette assay using IgG-coated sheep red blood cells. In RA patients, the percentage of monocytes forming rosettes was significantly lower than in controls (34.4 +/- 20.4 versus 67.4 +/- 4.5%; P less than 0.001). The blockade observed was reversed by a prior trypsin treatment of RA monocytes, the percentage of recovery being correlated with the IgG plasma levels. Besides, IgG purified from the serum of four RA patients bound a mean of 7.3, 5.2, 1.6, and 1.6 times more than normal IgG did onto concanavalin A (Con A), peanut agglutinin (PNA), phytohemagglutinin (PHA), and pokeweed mitogen (PWM), respectively. Although similar amounts of 125I-labeled normal and RA IgG were bound to normal monocytes, RA IgG inhibited more efficiently than normal IgG the Fc-R function of normal monocytes, for all concentrations tested (10 to 100 micrograms/100 microliters). A prior treatment of RA IgG by alpha-mannosidase, but not by beta-galactosidase, significantly reduced their inhibitory properties. The incubation of monocytes with D-mannose or mannan reduced their capacity to form rosettes. The percentage of monocytes forming rosettes in the presence of both mannan and normal IgG was significantly lower than that measured in the presence of normal IgG only. On the contrary, the rosetting capacity of monocytes in the presence of both RA IgG and mannan was the same as that calculated in the presence of RA IgG only. The inhibitory effect of RA IgG was not related to their abnormal circular dichroism. Our data suggest that the greater ability of RA IgG to block the Fc-R function of monocytes probably depends on the presence of a greater number of accessible mannosyl residues on the glycosidic side chains located in the Fc domain of the molecules. [less ▲]

Modifications des proteoglycans articulaires durant traitement par l'acide tiaprofénique

in Revue Médicale de Liège (1985), 40(17), 596-599

Treatment of active rheumatoid arthritis with slow intravenous injections of thymopentin

in Lancet (1985), 13(1), 832-836

41 patients with active rheumatoid arthritis entered a placebo-controlled double-blind randomised study in which 21 received slow intravenous injections (given in fractions over 10 min) of thymopentin ... [more ▼]

41 patients with active rheumatoid arthritis entered a placebo-controlled double-blind randomised study in which 21 received slow intravenous injections (given in fractions over 10 min) of thymopentin (TP·5) 50 mg 3 times a week for 3 consecutive weeks and 20 received placebo in the same way. After 3 weeks of treatment the TP-5 group showed improvement (p<O' 05 or p<O: 01) in all but one of the clinical variables tested. There was improvement in the number of joints painful at rest, the number of joints painful on motion, scores for tenderness on pressure and swollen joints, severity of pain on awakening and morning stiffness, and right-hand grip strength; left hand grip strength remained unchanged. In the placebo group, only morning stiffness improved significantly. [less ▲]

Measurement of proteoglycans, elastase, collagenase and protein in synovial fluid in inflammatory and degenerative arthropathies

in Clinical Rheumatology (1985), 4(1), 39-50

The number of leucocytes and the concentrations of protein, proteoglycans (PG), elastase a1 proteinase inhibitor complexes and collagenolytic activity were measured in the synovial fluid (SF) of 15 ... [more ▼]

The number of leucocytes and the concentrations of protein, proteoglycans (PG), elastase a1 proteinase inhibitor complexes and collagenolytic activity were measured in the synovial fluid (SF) of 15 patients with rheumatoid arthritis (RA) and 18 with osteoarthritis (OA). The mean levels of protein and collagenase and the number of leucocytes were higher in RA than in OA SF. However, the mean level of PG was higher of OA SF than in RA. In the latter, they were principally in the form of monomers and fragments while in the former they were in the form of aggregates and monomers. There was a direct relationship between the concentration of E-a/Pi and either the number of white cells or the concentration of synovial proteins, suggesting that the measurement of E-a/Pi complexes is a biochemical index of the local inflammatory reaction. There was an inverse correlation between the concentrations ofPG and E-a/Pi which may reflect the effect of degradation in PG of elastase and other enzymes released at the same time. Finally, there was a direct relationship between the concentration of E-a/Pi and collagenase which may be the reflection of a simultaneous release of various enzymes from leucocytes and macrophages. [less ▲]

Bilan minimum d'orientation dans le diagnostic immunologique

in Revue Médicale de Liège (1985), 40(8), 288-301

The Fc-receptor function of human mononuclear phagocyte system: physiological role, alteration in immune diseases and modulation

in Acta Clinica Belgica (1985), 40(1), 27-37

Circulating immune complexes (CIC) are detectable in high titer in patients with various immune diseases and the deposition of these complexes is believed to be important in the pathogenesis of these ... [more ▼]

Circulating immune complexes (CIC) are detectable in high titer in patients with various immune diseases and the deposition of these complexes is believed to be important in the pathogenesis of these disorders. The reticuloendothelial system (RES), which includes the KuptTer cells of the liver and the splenic macrophages, is involved in the removal of CIC from the vascular system. A defect in CIC clearance may enhance their tissue deposition. Accordingly, during the past few years, increased interest has been devoted to the measurement of immune clearance mediated by receptors for Fc, IgG coated autologous red blood cells (IgG-RBC) labelled with 51Cr have been used as immune tracer particles to follow the Fc-receptor function of whole RES in normal and pathological conditions. Prolonged clearance times of IgG-RBC are generally found in most immune complex-mediated diseases. Using IgG-RBC labelled with 99m Tc, it has been thereafter possible to determine not only the clearance half-time of the tracer, but also separated spleen and liver Fc-receptor binding capacities. It has been clearly demonstrated that the spleen to liver ratios per surface area (S/L s) are deeply pathological in immune disorders, even when clearance half-times (T 1/2) remain within the normal range. Abnormal ratios result from both a decreased splenic uptake and an increased liver uptake of IgG-RBC, this "hepatic compensation" preventing the T 1/2 to be out of the normal values. Abnormal T 1/2 are therefore observed only when the spleen and liver phagocytic capacities are saturated. The splenic Fc-receptor blockade is generally correlated with the disease activity and, less frequently, with the immune complex plasma levels. Serial measurements of S/Ls may be therefore of clinical interest by delineating those patients in whom the evolutivity of the disease is potentially high. Finally, serial S/Ls measurements have allowed the in vivo study of the modulation of the macrophagic Fc-receptor function by plasma exchange, corticosteroid administration and highdose gammaglobulin infusion. [less ▲]

Interim results on the clinical effects of i.v. administered thymopentin in active rheumatoid arthritis

in International Journal of Clinical Pharmacology, Therapy and Toxicology (1984), 4(6), 451-457

Forty-one patients with active rheumatoid arthritis entered a controlled, double-blind, randomized study; 21 received prolonged i.v. injections (10 min) of thymopentin 50 mg 3 times a week for 3 ... [more ▼]

Forty-one patients with active rheumatoid arthritis entered a controlled, double-blind, randomized study; 21 received prolonged i.v. injections (10 min) of thymopentin 50 mg 3 times a week for 3 consecutive weeks; the other 20 received placebo under the same conditions. The groups were comparable at the start of the study. Statistical tests of changes within the treatment groups after 3 weeks showed that the improvement achieved in the thymopentin group was significant (p less than 0.05 or p less than 0.01) for each clinical parameter, except for left-hand grip strength. On the other hand, no significant improvement was observed for any parameter except morning stiffness in the patients on placebo. The intergroup comparison showed significant differences, favouring thymopentin over placebo treatment, in the Ritchie index, scores for swollen joints, assessment of severity of pain and scores for changes in the activity of the disease. Only minor side-effects were experienced in the two treatment groups. The present placebo-controlled double-blind study confirms the previous positive results achieved in open studies, i.e., the beneficial therapeutic effect of prolonged i.v. injections of thymopentin in patients with severe rheumatoid arthritis observed after 3 weeks of therapy. The drug appears to be safe at the dose regimen used. [less ▲]