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The induction of lupus-like syndromes with the appearance of single-stranded DNA antibodies is a well-known complication of drug therapy. In this report we present a patient with an erosive seropositive rheumatoid arthritis developing the clinical and serological features of systemic lupus erythematosus including the occurrence of double-stranded DNA antibodies under sulfasalazine treatment.

The investigation of in vitro platelet functions from patients with SLE and rheumatoid arthritis (RA) revealed a distinctly reduced aggregation mass after both collagen und ADP induction. The platelet serotonin contents were significantly decreased in both groups. An "aspirin-like" platelet defect could be excluded by finding a normal malonyldialdehyde release of patients' platelets upon thrombin stimulation. Significantly increased platelet associated IgG was also detected, whereas platelet associated IgM remained within normal limits. These results are interpreted as indicating an ongoing platelet release reaction induced by IgG platelet antibodies, which induce the observed impairment of platelet functions and may also lead to the release of proinflammatory platelet mediators.

Fifty-one patients with rheumatoid arthritis were examined at 6-month intervals during a 2-3-year investigation period. Correlations of an inflammatory activity index calculated from nine criteria with several laboratory parameters were computed. ESR correlated most closely, followed by the IgM concentration of circulating immune complexes, hemoglobin, C3A, and fibrinogen.

Resting blood flow, spontaneous variations of resting blood flow and postischemic peak flow of the fingers, measured by venous occlusion plethysmography, were reduced in patients with rheumatoid arthritis (n = 39) as compared to normals (n = 18). Resting blood flow and postischemic peak flow were reduced only in patients without skin vessel wall immune complex (IC) deposits, whereas spontaneous variations of resting blood flow were found to be reduced in patients with IC deposits. However, after inducing sympathicolysis, postischemic peak flow was reduced in both groups. These findings were consistent with the presence of organic lesions of the finger arteries in both groups associated with additional functional vasospasm in patients without complex deposits, that in the other group may have been counteracted by the presence of IC deposits.

Rheumatoid arthritis (RA) as a systemic disease can attack many other organs in addition to the joints. A variety of pathological lesions of the blood vessels are responsible for the extra-articular features (EAF). In the present study, we investigated firstly whether the presence of blood vessel changes in one organ--namely the skin--may indicate blood vessel pathology and, consequently, EAF in other organs. Secondly, we investigated the number of EAF in individual patients with RA, and observed whether this changed during the course of the disease. Fifty-one RA-patients (40 female, 11 male; ages had a mean of 49.5, minimum 19, maximum 73 years; mean duration of RA was 7.3, minimum 0.25, maximum 41 years) were included in the study. Punch biopsies from the posterior calf were examined immunohistologically for vessel wall immune deposits. Further, EAF were determined by means of instrumental clinical methods such as pulmonary function test, echocardiography, electromyography, and nerve conduction velocity measurement. At the first investigation 21/51 patients had skin vessel wall immune deposits (SVWID). Five patients--all showed SVWID at first investigation--died during the three-year investigation period, 10 patients could not be followed-up for unknown reasons; the skin biopsy of one patient could not be assessed. At the final investigation, we found SVWID in 11/35 patients. SVWID-positive patients had more EAF compared to SVWID-negative patients; this was true both, at the first investigation (1.85 EAF/patient vs 1.05 EAF/patient) and at the final investigation (1.91 EAF/patient vs 0.67 EAF/patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Using sera from patients with rheumatoid arthritis and antiglobulin preparations obtained from such sera, inhibition of human lymphocyte cytotoxicity in antibody-dependent (ADCC) and spontaneous cell-mediated cytotoxicity (SCMC) reactions against an allogeneic melanoma cell line (IGR3) has been demonstrated. Fractionation of effector cell preparations indicated that Fc-receptor-bearing lymphocytes were operative in both reactions. Removal of phagocytic and adherent cells from the effector cell population resulted in more pronounced inhibition of SCMC and ADCC reactions by rheumatoid sera. The results indicate that antiglobulin preparations from human sera containing rheumatoid factor activity can effectively block the cytotoxic activity of Fc-receptor-bearing effector lymphocytes (K cells) in vitro. On analogy with the inhibition of ADCC and SCMC reactions by immune complexes and aggregated IgG, antiglobulin complexes present in the antiglobulin preparations are responsible for this effect.

Fifty-one rheumatoid arthritis patients were examined prospectively during a 3-year investigation period by means of immunohistological, histological, and instrumental clinical methods. Skin vessel wall immune deposits (SVWID) were found in 21/51 patients at the first and in 11/35 patients at the concluding investigation. Patients with SVWID showed more extra-articular features, more rapid progress of joint damage, higher mortality frequency, higher inflammatory activity, and higher levels of circulating immune complexes, compared with patients without SVWID.

Activation of the complement system via immune complex formation plays an important role in the perpetuation of chronic inflammatory disorders. The serum levels of C3 or C4 do not necessarily reflect the actual complement catabolism. By measurement of the long-lived C3 split product "C3d" direct information about complement activation can be obtained. C3d was measured with a modified immunoelectrophoresis technique in EDTA-plasma of 106 patients with rheumatoid arthritis. 36% of them showed significantly elevated C3d levels (mean: 8.93 micrograms/ml). Significant linear correlations were found for C3d with ESR, Lansbury-Index and plasma viscosity.

In vitro transofrmation of peripheral blood lymphocytes (PBL) by phytohaemagglutinin (PHA) and concanavalin A (Con A) was found to be decreased in 17 RA patients. The addition of 50 microliter RA serum or serum from normal controls exhibited an inhibitory effect on the mitogenic reactivity to Con A but not to PHA of both normal and RA patient's PBL. Allogeneic antiglobulin preparations (a-Ig) stimulated the spontaneous in vitro DNA synthesis of PBL from normal control and, to a smaller degree, also from RA patients. The simultaneous addition of a-Ig's and mitogens to PBL of normal controls and RA patients did not exhibit a significant effect on the mitogenic reactivity.

Sera from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were assessed for in vitro platelet activation as measured by serotonin release; 24% (30) of 124 tested RA sera and 51% (35) of 69 SLE sera induced a significant 3H serotonin release. Investigation of 17 synovial fluid samples from RA patients revealed significant release in 82%. Concomitant testing for lymphocytotoxic antibodies and immune complexes did not show any correlation to platelet activation. Upon gel filtration the release-inducing activity of positive sera was localized in the region of 160 000 Daltons. Further characterization by ion exchange chromatography, immune electrophoresis, chromatographic and SDS PAGE molecular weight determinations, as well as analytical ultracentrifugation all confirmed the IgG nature of the release-inducing protein. Negative blocking experiments performed by preincubation of platelets with Fc-IgG fragments prior to challenge with a release-inducing serum excluded the participation of Fc receptors in the reaction. It was concluded that the release was caused by a platelet reactive IgG antibody. This antibody may also cause release of platelet mediators in vivo and may thus contribute to the pathogenesis of the generalized vasculopathy in both diseases.

Circulating immune complexes were determined in rheumatoid arthritis and systemic lupus erythematosus using a semiautomated PEG-precipitation laser-nephelometer technique. Immunoglobulins IgA, IgG and IgM as well as complement proteins C3c and C4 were quantitatively determined in 2.75% PEG-precipitates. The PEG-precipitates obtained from the sera of healthy controls, SLE patients, and RA subjects displayed different protein patterns. In RA sera a significant elevation of all investigated proteins was found. In SLE sera, a significant increase of IgG, IgA, IgM, and C3 was found, whereas C4 was significantly reduced as compared to the controls. Typical values for a calculated IgG/C4 ratio in circulating immune complexes were obtained for RA and SLE. In RA this ratio remained unchanged in different activity stages and was found in seropositive as well as in seronegative sera. Thus circulating immune complexes from SLE and RA sera differ with respect to the degree of complement-dependent solubilization.

In addition to the well-known rheumatoid factors or antiglobulins belonging to different immunoglobulin classes, a new type of antiglobulin has been found in serum and synovial fluid from patients with rheumatoid arthritis. 15/20 sera and 6/6 synovial fluids contained serologically active material with a molecular weight of approximately 95.000 Daltons. Using chromatographic and affinity chromatographic methods as well as specific precipitation techniques, the (Fab')2 character of these antiglobulins could be ascertained. These antiglobulins may arise through enzymatic degradation of IgG or monomeric IgM antiglobulins, or may be the product of partial intracellular degradation of phagocytosed immune complexes with subsequent extrusion of such material. An in vitro blocking effect of (Fab')2 type antiglobulins on SCMC or ADCC reactions was not found.

Antiglobulin factors of the IgG class were measured in human sera by a modified immunoadsorbent-technique involving absorption to and elution from insoluble preparations of horse IgG. 32 mg of horse IgG insolubilized with bisdiazotized benzidine were used for quantitative immunoadsorption of IgG antiglobulins from 100 mul serum. Different IgG-antiglobulin concentrations could be obtained in two control groups differing in age. Elevated IgG-antiglobulins levels were found both in seropositive (mean value 23.21 +/- 7.08 mug/ml serum) and seronegative (mean value 20.06 +/- 8.39 mug/ml serum) RA patients. High values of IgG-antiglobulins were found in chronic liver disorders, particularly in the group of CAH patients (mean value 25.10 +/- 6.1 mug/ml serum).

Soluble circulating immune complexes (CIC) are a common finding in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) or other autoimmune diseases. The predominant immunoglobulin class of most CIC is IgG, which enables these CIC to bind to Fc-IgG-receptor expressing cells. In this study the interaction between soluble CIC from patients with SLE or RA and Fc-IgG-receptor positive lymphoid cells from healthy individuals was investigated. Similar to the effect observed with insoluble immune complexes, soluble CIC interact with Fc-IgG-receptor positive lymphoid cells and can induce a modulation of Fc-receptor expression. Fc-IgG-receptors are lost and Fc-IgM-receptors are expressed on the same cells after IC interaction and culturing the cells for 24 h. Simultaneously with this change of Fc-receptor phenotype the originally Fc-IgG-receptor positive cells demonstrate a decreased ability to proliferate upon mitogen stimulation. This change of phenotype and proliferative capacity correlates with the content of CIC in the sera of patients with SLE or RA.

Antiglobulin complexes were isolated from rheumatoid arthritis (RA) sera in order to investigate their ability to aggregate human platelets and to influence platelet aggregation induced by heat-aggregated IgG. Eleven of 38 seropositive RA sera showed a significant platelet aggregation (PA) titer as compared to 40 normal control sera. No correlation was observed between sheep T cell agglutination titers and PA titers of individual sera. Ten of 22 RA antiglobulin preparations containing IgG, IgM, and IgA antiglobulins and antiglobulin complexes also showed positive PA tests. Such preparations were able to inhibit PA brought about by heat-aggregated human IgG. When IgG and IgM antiglobulins were tested separately, only IgM antiglobulins showed this inhibitory effect, whereas IgG antiglobulins were inactive. Neither IgG nor IgM antiglobulins induced PA alone. Reassociated IgG antiglobulin complexes consisting of carefully prepared IgG and isolated IgG antiglobulins were able to induce PA. Platelet aggregation by RA sera was thus shown to be due to IgG antiglobulin complexes present in the sera. It can be concluded from these experiments that the composition of antiglobulin complexes in individual sera comprised of antiglobulins of different classes and IgG "antigen" is responsible for PA results in vitro. In pathophysiologic terms, the reaction of IgG antiglobulin complexes with thrombocytes in vivo may be an important step in the chain of events leading to generalized vascular damage and deposition of immune complexes in vessel walls which is thought to be responsible for the development of generalized vasculitis in RA.

The investigation of in vitro platelet functions from patients with SLE and rheumatoid arthritis (RA) revealed a distinctly reduced aggregation mass after both collagen und ADP induction. The platelet serotonin contents were significantly decreased in both groups. An 'aspirin-like' platelet defect could be excluded by finding a normal malonyldialdehyde release of patients' platelets upon thrombin stimulation. Significantly increased platelet associated IgG was also detected, whereas platelet associated IgM remained within normal limits. These results are interpreted as indicating an ongoing platelet release reaction induced by IgG platelet antibodies, which induce the observed impairment of platelet functions and may also lead to the release of proinflammatory platelet mediators. [ABSTRACT FROM AUTHOR]