Gunnar Bendixen

A new model for classification of disease manifestations in primary Sjögren's syndrome: evaluation in a retrospective long-term study.

Objectives. The clinical features of 80 patients with primary Sjögrens syndrome (PSS) were revised in order to evaluate the descriptive and analytical facilities of a newly proposed model for classification of the exocrine and nonexocrine disease manifestations in PSS.

ANTI‐PANCREATIC, CELLULAR HYPERSENSITIVITY IN DIABETES MELLITUS. ANTIGENIC ACTIVITY OF FETAL CALF PANCREAS AND CORRELATION WITH CLINICAL TYPE OF DIABETES

Lymphocytic infiltration in and around the islets of Langerhans is a characteristic feature of juvenile diabetes mellitus of short duration (5, 6). The significance of this phenomenon still remains to be elucidated, but the observation is from the theoretic point easy to associate with the finding of anti-pancreatic, cellular hypersensltivity in diabetes mellitus (8), and both features suggest that celi-mediated immunity may play a role during the initial pathogenic phase of juvenile diabetes. In our preliminary work the anti-pancreatic, cellular hypersensitivity was demonstrated in patients with diabetes mellitus by means of the leucocyte migration test (LMT) (2) with a preparation of duct-ligated, porcine pancreas as antigen. The number of patients with diabetes examined, however, was small. The purpose of the present study has been: I) By means of the L M T to asses the occurrence of antipancreatic, cellular hypersensitivity in diabetes, using a pancreatic antigen prepared from another species.

AN IN VITRO ASSAY OF LEUKOCYTE MIGRATION INHIBITORY ACTIVITY FROM HUMAN LYMPHOCYTES STIMULATED WITH CONCANAVALIN A

Human venous blood lymphocytes, incubated for 22 h in serum-free culture medium with the plant mitogen concanavalin A (Con-A), elaborated products, which inhibited the migration of human buffy coat cells under agarose. Con-A was removed by applying the supernatants on small Sephadex G-100 columns. The leukocyte migration inhibitory activity (LMIA) was tested in a semi-quantitative modification of the indirect leukocyte migration agarose technique, which is described. Lymphokine activity, demonstrable as early as 9 h after activation of lymphocytes, was most pronounced after 22 h. Significant LMIA was demonstrated in 12 of 17 normal individuals at standard dilution of culture supernatants I/3. In 9 of the 12 experiments, assays of LMIA were carried out on stepwise diluted supernatants with detection of the greatest dilution with significant LMIA. In four experiments LMIA could only be detected after 3- to 12-fold concentrations of supernatants. Considerable individual variation was found, the amounts of LMIA varying by a factor of about 300. The reproducibility appeared to be quite high, but the factor stability of supernatants stored at -20 degrees C was surprisingly low.

Quantitative Assessment of Clinical Disease Status in Primary Sjögren's Syndrome

Quantitative and qualitative assessment of the clinical disease manifestations in 41 primary Sjögrens syndrome (pSS) patients was performed according to a new classification model. Frequencies of subgrouped disease manifestations were as follows: 1) surface exocrine disease: 100%, 2) internal organ exocrine disease: 63%, 3) monoclonal B lymphocyte disease: 5%, 4) inflammatory vascular disease: 71%, 5) non-inflammatory vascular disease: 59%, 6) mediator induced disease: 98%. Summary scores for severity of surface exocrine disease correlated to the summary scores of all other disease manifestations (p = 0.02), to the summary scores of internal organ exocrine disease (p = 0.003), and to the summary scores of mediator induced disease (p = 0.03). Blood leucocyte counts showed significant negative correlations to levels of plasma IgG, serum IgA-RF, IgM-RF, anti-SSA/SSB antibodies, IL-6, and IL-1Ra. We conclude that the model made detailed analysis of the clinical presentation of pSS possible, and thus may assist in elucidating important pathobiological aspect of the disease.

Lymphokines and thrombosis. I. Thrombocyte aggregating activity released by human lymphocytes stimulated with concanavalin-A.

Supernatants from Con-A stimulated human lymphocytes containing leucocyte migration inhibitory activity were measured for thrombocyte aggregation activity and for influence on thrombocyte rich plasma clot retraction and whole blood clot retraction. The lymphocyte released activity of the supernatants produced thrombocyte aggregation and an acceleration of clot retraction. The activity resisted heating at 56 degrees C for 30 min and was inactivated at 80 degrees C for 30 min. The active substance seems to have a molecular weight above 10,000 daltons. The findings suggest that thrombotic processes associated with cell-mediated (type IV) immune inflammation could be due, at least partially, to lymphokine effects on thrombocytes.

LYMPHOKINES AND THROMBOSIS II. Procoagulant Activity Produced by Human Lymphocytes Stimulated with Concanavalin A (Con-A)

Human lymphocytes stimulated with concanavalin-A produce a coagulant activity which decreases the clotting time as expressed through the recalcification time of citrated plasma, the partial thromboplastin time, the thrombin clotting time of citrated plasma and the thrombin clotting time of fibrinogen solutions. The culture supernatants of human lymphocytes stimulated with concanavalin-A also have a direct coagulant effect on human fibrinogen solution. They decrease the lag period of recalcification time of citrated plasma but do not modify the duration of polymerization as measured with a spectrophotometric method.

Increased expression of complement receptor type 1 (CR1, CD35) on human peripheral blood T lymphocytes after polyclonal activation in vitro

The receptor for C3b and C4b—complement receptor type 1 (CR1, CD35)—is present on a variety of cell types including erythrocytes, phagocytic cells, B lymphocytes and a small sub-population of T lymphocytes. The function of the receptor varies according to the different cell types, but a T lymphocytes the function is as yet not known. The present study concerns the influence of polyclonal stimulation on CR1-expressing T lymphocytes. Incubation with PHA resulted in a dose-dependent increase in the number of CR1-positive T lymphocytes. The CR1-expression T lymphocytes were found in both the CD4- and the CD8-positive subpopulation, but a significant stimulatory increase was only found in the CD4-positive population. A significant increase in the number of CR1-expressing T lymphocytes was found when monocytes were present during stimulation, indicating an importance of monocytes and/or monocyte products. However, the increase was not regulated by arachidonic acid metabolites of the cyclo-oxygenase pathway as indomethacin failed to inhibit the increase. Neither did rIL-Iα, rIL-1β, rTNFα nor rIL-6 alter the number of CR1-expressing T lymphocytes. The results of this study indicate a role for CR1 on T lymphocytes in the regulation of the immune system.

Lack of evidence for human lymphokines with thrombocyte aggregating activity. An in vitro study

The ability of human lymphocytes to produce soluble mediator(s) with thrombocyte aggregating activity (TAA) was investigated in an in vitro technique. Isolated human mononuclear cells were stimulated with phytohaemagglutinin or purified protein derivative of tuberculin. The supernatants were investigated for lymphokine activity in a leucocyte migration inhibitory factor assay. Supernatants were then tested for their ability to aggregate human thrombocytes, and in contrast to the results of previous studies, we were not able to demonstrate any TAA. Most likely, lymphokines with TAA are not involved in the thrombotic processes seen in human cell‐mediated immune inflammatory reactions.