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A 64-year-old man presented with symptoms of systemic immune disease dominated by rapidly progressive glomerular injury with highly positive ANCA of cytoplasmic distribution. The clinical course was characterized by dependence upon the intensity of immunosuppression, which has finally led to development of fungal septicaemia and death. The post mortem examination revealed occult gastric cancer with regional lymphatic involvement and crescentic glomerulonephritis, while failing to substantiate clinical findings of systemic vasculitis. This is, to our knowledge, the first case of ANCA-positive glomerulonephritis accompanying visceral malignancy and as such raises the question of whether it results from a simple coincidence or a causal relationship.

Angiotensin converting enzyme inhibitors was given to 16 patients with glomerular nephritis in whom a complete remission of nephrotic syndrome could not be achieved with immunosuppressive-anti-inflammatory therapy. Captopril in the daily dose of 25-75 mg and enalapril in the daily dose of 10 mg were administered for 1-36 months (mean 12.6 months). Daily proteinuria decreased by 40-80% comparing with baseline value in 2/3 of patients. Total protein and albumin serum levels increased simultaneously. No changes in blood creatinine were noted in patients with initially normal renal functioning except one patient. Renal functioning was stable in 50% of patients with increased blood creatinine levels (mean 200 mumol/L). Blood creatinine was increasing in the remaining patients.

Just as in other inflammatory processes in glomerulonephritis also a great role has been ascribed recently to proteases released from phagocytes and mesangial cells. On the basis of original observation (clinical and experimental) of glomerulopathy inhibition by EACA, the authors present the concept of local antiproteolytic failure as the cause of protracted course of certain forms of glomerulonephritis.

A study was carried out to verify the clinical usefulness of the elaborated method for the measurement of antistreptococcal antibody in revealing the streptococcal etiology of glomerulonephritis. In 158 patients with glomerulonephritis antistreptococcal antibody (ASA), circulating immune complexes (CIC) and haemolytic activity of the complement were measured. On the basis of immune complex formation it has been concluded that streptococcal infection may cause glomerulonephritis. Serial determinations of ASA and CIC are helpful in establishing the streptococcal etiology of glomerulonephritis and in monitoring the course of the disease.

Monocytes of 95 patients with chronic glomerulonephritis (ch.g.) tested in vitro demonstrated characteristics of activation in proliferative, and of functional suppression in mesangiocapillary glomerulopathy. Fc and C3 receptor function studied by rosette assay and metabolic potential measured by the NBT reduction test constituted result patterns. Receptor tests were supplemented with their counterparts after monocyte triggering with heat-inactivated sera and in case of NBT assay - stimulation with zymosan. Membranous, minimal change, mesangial and focal glomerulonephritis monocytes presented less specific configurations of data than those of proliferative and mesangiocapillary, with a uniform increase of trypsin-resistant Fc receptor activity. There was no appreciable correlation between the presence of circulating immune complexes (c.i.c.) in patient sera and parameters tested. The mesangiocapillary "suppression pattern" suggests mononuclear phagocyte defect in this glomerulopathy.

Studies on the adenosine deaminase (ADA) and aldolase activities in lymphocytes were performed in 67 patients with glomerulonephritis (gn) and in 20 healthy individuals from the control group to get an insight into the lymphocyte metabolism. Statistically significant decrease of ADA activity was found in the groups of patients with chronic proliferative gn, membranoproliferative gn, membranous gn and lupus nephritis in comparison with the healthy individuals from the control group. As far as decrease of aldolase activity is concerned it has reached statistical significance in patients with mesangial gn, membranoproliferative gn, membranous gn and lupus nephritis. The lymphocyte metabolism did not show any abnormalities in the enzymatic indicators only in patients with acute proliferative gn and submicroscopic gn. The activity comparison between both enzymes in the lymphocytes, contrasted on the basis of high and low clinical dynamics of gn, revealed a tendency to lower ADA and aldolase activities in patients with high clinical dynamics. However, this difference was at the limit of statistical significance (p less than or equal to 0.10).

The effect of immunosuppressive and anti-inflammatory drugs on the T and B lymphocyte populations, as well as cellular hypersensitivity in relation to GBM antigens (measured by MIF activity) in 60 patients with different types of glomerulopathy has been tested. The results were compared with a control group of 47 untreated patients and 32 healthy subjects. The treatment was carried out using the following drugs: azathioprine, cyclophosphamide, prednisone, ibuprofen and indomethacin. In a sample of 14 patients receiving ibuprofen and in 7 receiving arathioprine, indomethacin and prednisone, the T and B lymphocyte kinetics as well as MIF activity were repeatedly tested before and during the treatment of 150 days. In the patients under this treatment, a decreased percentage of lymphocytes with receptors for a complement as well as, in some cases. MIF suppression was observed. A comparison of healthy subjects and untreated patients with a group of 39 subjects tested for T and B lymphocytes as well as MIF activity after several months of the above treatment was made. It was found that supportive therapy with azathioprine and prednisone led to a normalization of B lymphocytes (EA and EAC rosettes) and to a small increase of T lymphocytes number. On the other hand, treatment with indomethacin and ibuprofen led to an increased B lymphocyte count (EA and EAC rosettes). Cyclophosphamide given with azathioprine caused a decrease in the proportion of T lymphocytes and an increase in the number of null cells. In addition, it was found that immunosuppressive drugs as well as anti-inflammatory drugs, even when administered in supportive doses caused in some cases, the suppression of cellular immunity as measured by MIF activity.

The aim of this work was to determine the activity of helix-destabilizing protein (HD-protein), which is indispensable in basic genetic processes such as DNA replication, genetic recombination and transcription, in lymphocytes of patients with different morphological types of glomerulonephritis and with chronic renal insufficiency, treated conservatively and by maintenance hemodialysis. The estimation was done on 44 patients with glomerulonephritis and on 20 patients with chronic renal insufficiency. The control group consisted of 20 healthy individuals. The investigations prove the fact that in human lymphocytes helix-destabilizing protein occurs, and its quantity enables us to determine its activity in the diseased and healthy state. Measurement of HD-protein activity seems to be a good marker of the altered lymphocyte function. Especially high HD-protein activity was noticed in cases of acute glomerulonephritis, lupus glomerulonephritis and in the active forms of chronic glomerulopathies. Generally, the tested parameter showed a positive correlation with the activity of the glomerulonephritic process. In lymphocytes of patients with chronic renal insufficiency treated conservatively, a greater activity of helix-destabilizing protein occurred than in the control group. Lymphocytes from patients with chronic renal insufficiency, treated with repetitive maintenance hemodialysis, did not reveal significant differences in HD-protein activity, determined directly before hemodialysis and after its completion, in comparison to the control group of healthy individuals.

143 patients were evaluated clinically on the basis of the renal biopsy. Three methods for detecting circulating immune complexes (CIC) were employed: complement consumption test, inhibition of erythrocyte antibody IgG-EA rosette forming test and optical density of 4% PEG precipitated sera. CIC were present in the sera of all patients with acute poststreptococcal glomerulonephritis (2 weeks after streptococcal infection of the throat). In a group of patients with chronic glomerulonephritis the highest values in positive results were observed in lupus nephritis, chronic proliferative glomerulonephritis and chronic submicroscopic glomerulonephritis. These results were compared with levels of total hemolytic complement, C3, C4 components and serum immunoglobulins (IgA, IgG, IgM).

Lymphocyte suppressive activity after stimulation with Con A and lymphocyte function as the effectors in the ADCC test had been examined in 68 patients with chronic glomerulonephritis (GN) and in 20 healthy controls. Lymphocyte suppressive activity was lower in patients with chronic GN than in the healthy individuals. In regard to chronic proliferative GN and mesangial GN the difference was statistically significant. The lymphocyte efficiency in the ADCC test was generally adequate in patients with chronic GN and none of the morphological types showed significant deviation from the control group. In the general analysis of patients with chronic proliferative, mesangial, membrano-proliferative and membranous GN a decrease of lymphocyte suppressive activity below the lower standard limit has been detected (45% of cases). A similar defect in lymphocyte function in the ADCC test has been found in 18.6%. A statistically significant relationship between the lymphocyte function disorders and the high clinical dynamism of GN has been noticed, although in some cases there was a deviation from this tendency. It is supposed that circulating immune complexes, detected in some patients with chronic GN are not the only decisive factors responsible for defects in lymphocyte function.

In vitro reactivity of lymphocytes to phytohemagglutinin (PHA) and pokeweek mitogen (PWM) was studied in 17 patients with chronic glomerulonephritis treated systematically over many months (average, 23 months) with immunosuppressive drugs (prednisone, indomethacin, azathioprine, cyclophosphamide). Blastic transformation of lymphocytes in cultures stimulated with PHA was tested three times: before beginning of treatment, during the course of therapy with full doses, and after prolonged ambulatory treatment with maintenance doses. The degree of blastic transformation under the influence of PWM was determined only after periods of many months of treatment with chemical immunosuppresors. The results showed that neither treatment of chronic glomerulonephritis for several weeks with full doses, nor subsequent prolonged administration (for periods of tens of months) of maintenance doses of immunosuppresors regularly inhibit blastic transformation of lymphocytes stimulated with PHA. Similar observations were made using PWM after many months of immunosuppressive therapy. Reactivity of lymphocytes to PWM in all patients resembled reactivity to PHA.

Studies were performed on 79 subjects, out of which 32 belonged to the control group and 47 suffered from glomerulonephritis. The number of T and B lymphocytes in peripheral blood was determined using the technique of E, EA and EAC-rosette tests. Also, the lymphocyte blast response to non-specific mitogens (PHA, Con A, PWM) was established in vitro. Patients suffering from acute proliferative glomerulonephritis, as compared to the control group, displayed a statistically significant increase of lymphocytes with the receptor for complement (EAC-rosettes). Their reactivity to all three mitogens did not differ from the values obtained in the control group. In patients suffering from chronic glomerulonephritis (proliferative, membranous-proliferative, membranous), shiftings in the contents of the peripheral blood lymphocytes pools were of opposite directions, i.e., statistically significant in comparison with the control group. Also an increase in the absolute number of T lymphocytes (E-rosettes) was observed. Generally speaking, the values of blast transformations after mitogen stimulations were smaller in patients suffering from chronic than in those suffering from acute glomerulonephritis. In 1/3 of them, the decrease of blast response to one of the three mitogens was detected. The decrease exceeded the lower limit of values of healthy subjects, and most often, it was connected with Con A stimulation.

Blastic transformation of peripheral blood lymphocytes following stimulation with phytohemagglutinin during immunosuppressive therapy (prednisone 2 mg/kg body weight, indomethacin 2--3-5 mg/kg, azathioprine 2--4 mg/kg, cyclophosphamide 1-5--3 mg/kg per day) was studied in 59 patients with various morpholigic forms of chronic glomerulonephritis and in 7 with lupus erythematosus nephritis. No uniformly regular influence of immunosuppressive therapy in the doses employed in glomerulonephritis on blastic transformation in in vitro cultures was noted. The specific drug administered was not decisive for the character of the change in reactivity of lymphocytes (increase or decrease in blastic transformation). The interesting observation was made that efficacy of treatment was high in patients with lowest initial values of blastic transformation and its greatest increase during therapy. Apparently, disorders of cellular immunity assessed on the basis of blastic transformation of lymphocytes stimulated with phytohemagglutinin are not a decisive prognostic factor in glomerulonephritis. The results are discussed from the aspect of a possible influence of immunosuppressive therapy on restoration of the physiological proportion of T and B lymphocytes in peripheral blood.

The function of polymorphonuclear neutrophils in two groups of patients with glomerulonephritis was investigated. Patients were divided according to renal efficiency. In the group of 37 patients with renal failure a decrease in chemotactic activity, phagocytal index and iodination activity of leukocytes was observed (as compared with the control group). Our data indicate that renal insufficiency has some influence on the activity of polymorphonuclear neutrophils.