Lymphocyte function and chromosome aberrations in patients with early mycosis fungoides and parapsoriasis en plaques.

Thirteen patients with stage I or II mycosis fungoides (MF) and 10 patients with large-plaque parapsoriasis en plaques (PEP) were examined for immunologic and cytogenetic disturbances. Total lymphocyte counts and immunoglobulin concentrations in the blood were normal. In vitro lymphocyte responses to polyclonal activators and various antigens in standard concentrations were normal. However, titration of phytohemagglutinin and concanavalin A (ConA) disclosed significantly lowered responses to suboptimal concentrations in the patient group, most pronounced in patients with MF II. ConA-induced leukocyte migration inhibitory factor (LIF) production, tested in an indirect leukocyte migration inhibitory assay, was low in the patient group. Furthermore spontaneous LIF production in vitro and small amounts of serum LIF were demonstrated in a few patients. The chromosomal banding pattern, sister chromatid exchange, and break frequency were within normal limits except for 3 translocations in the MF group. It is concluded that even in early-stage MF a pathologic function of blood lymphocytes can be demonstrated, when sensitive methods are applied. The findings might be important for monitoring disease activity and effect of treatment.

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 subpopulation of T lymphocytes. The function of the receptor varies according to the different cell types, but on 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-1 alpha, rIL-1 beta, rTNF alpha 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.

A microtiter plate enzyme-linked immunosorbent assay for measuring C3b receptors on human erythrocytes.

An enzyme-linked immunosorbent assay was developed for quantitation of complement C3b receptors (C3bR) on human erythrocytes fixed in monolayer to microtiter plates. The disadvantages of macro test tube systems (large consumption of sample material and reagents, tedious washing procedures, cell loss and hemolysis) were avoided, and the fixed cells could be stored. In return a modest reduction in antigenicity induced by glutaraldehyde was inevitable. The calibration curve expressed a detection limit of about 10% and discrimination between levels of C3bR in the interval of about 10-120% of a standard erythrocyte with a high uptake of anti-C3b-receptor antibodies. The determinations of C3bR in normals as well as in patients varied within these limits, and showed a preponderance of low levels in the patients. The between-day coefficient of variation was 10.3%; the within-assay interplate and intraplate determinations respectively gave coefficients of variation of 9.7% and 6.2%. The method is suitable for further development and use for investigation of erythrocyte-bound immune complexes.

Discussion paper: tumor-directed cellular hypersensitivity detected by leucocyte migration in patients with renal carcinoma.

Leucocyte migration inhibition detected in vitro by the capillary tube technique (LMCT) has proved a useful tool for detection of tumor-specific cell-mediated hypersensitivity (TCMH) in man. Investigations in pateints with renal tumors are reported. It is shown that TCMH is a feature of hypernephroma in man, that the antigenic specificity is found in autologous as well as allogeneic tumor tissue and in fetal kidney tissue. The pattern of reactivity compared to postoperative survival and occurrence of metastases and postoperative clinical course shows a clear association between TCMH and tumor elimination. The capacity of hypernephroma patients to develop a cell-mediated immune response is generally not reduced. In allogeneic combinations, small noninvading tumors usually have a high antigenicity, whereas tumors with early dispersion show a low antigenicity. The development of TCMH and associated tumor elimination therefore may be depending preferably on the antigenicity of the tumor, less on the immune capacity of the tumor host.

Immunological studies in sarcoidosis: a comparison of in vivo and in vitro Kveim tests.

No migration inhibition was observed in the 46 patients or the 12 controls when the Danish Kveim antigen was used in the LMAT. No migration inhibition was found in 23 of the same patients when the LMT was employed using the same antigens (Table 3).

Immunological studies in sarcoidosis: a comparison of disease activity and various immunological parameters.

We found it valuable to separate the heterogeneous types of sarcoidosis into more homogeneous groups on the basis of activity and duration of the disease. This view is supported in the present study by the finding of a marked depression of T-cell function in patients with chronic-active sarcoidosis. Patients with acute or chronic-inactive disease had only moderately depressed T-cell function as measured by tuberculin skin test and DNCB index. These results are in agreement with those of some previous investigations. The remainder of the abnormal findings, particularly low total number of circulation T lymphocytes, elevated serum IgG levels, and presence of autoantibodies, could not be correlated to disease activity, extent of the disease, or T-cell function. We have found no explanation for the presence of autoantibodies but suspect that they may be nonspecifically related to the disease process.

[Systemic lupus erythematosus. 1. Disease manifestations, infections, thrombotic episodes, causes of death and survival in a case load of 173 patients followed for 13.9 years]. / Systemisk lupus erythematosus. 1. Sygdomsmanifestationer, infektioner, trombotiske episoder, dødsåger og overlevelse i et materiale bestående patienter fulgt i gennemsnitlig 13,9 år.

One hundred and seventy-three patients had systemic lupus erythematosus according to the 1982-ARA-criteria. The mean disease duration at the time of the study was 16.4 years, and the patients were followed by three Copenhagen clinics for a mean of 13.9 years until 1987/88 or death. Half of the patients had nephropathy, 61 patients developed severe infections, and 39 patients had thrombotic episodes. Fifty-six patients died during the observation period, 24 due to active lupus (12 of kidney failure), 12 because of infections, and 11 because of atherosclerotic cardio-vascular disease. The patients had 10-, 15- and 20-year survival rates of 80, 65 and 48 per cent. The deaths were evenly distributed throughout the observation period.

[Systemic lupus erythematosus. 2. Factors of predictive significance for survival]. / Systemisk lupus erythematosus. 2. Faktorer med praediktiv betydning for overlevelsen.

Sixty-one of 173 patients with systemic lupus erythematosus followed for a mean of 13.9 years had severe infections which influenced their survival more than could be accounted for by the mortality (20 per cent) caused by the infections. Patients with infections had more SLE manifestations than patients without infections, and they died of lupus manifestations more often than patients without infections. Patients who went into a permanent remission and patients who died of lupus differed most markedly by the rates of infection. The rate of infection was increased more than tenfold in patients treated with high dosages of glucocorticoid compared with patients who received low dosages. Treatment with cytostatics influenced the rate of infections to a moderate degree. Nephropathy also influenced survival but half of the patients with nephropathy maintained a normal plasma creatinine in spite of the long observation period. 16 per cent of the patients with nephropathy died of kidney failure or are receiving chronic hemodialysis.