Lennart Nässberger

Autoantibodies against neutrophil cytoplasm components in systemic lupus erythematosus and in hydralazine‐induced lupus

Anti‐neutrophil cytoplasm antibody (ANCA) has been shown to be no marker of systemic lupus erythematosus (SLE) including lupus nephritis or of progressive systemic sclerosis (PSS). Antibodies against myeloperoxidase (anti‐MPO) and elastase, two granulocyte lysosomal enzymes, were found in patients with SLE but not in those with PSS, except for one patient who had anti‐MPO. Anti‐MPO was present in 21% of patients with SLE, and at low concentrations in about 80% of these cases. Anti‐elastase was found in four patients with SLE. In another group of six patients with a SLE‐like syndrome induced by anti‐hypertensive treatment with the anti‐hypertensive hydralazine, anti‐MPO antibodies occurred in all six, and anti‐elastase antibodies in five. Monitored during a 2‐year follow‐up period, anti‐MPO antibodies were found to persist, whereas anti‐elastase antibodies were rapidly eliminated, after withdrawal of the drug.

Circulating granulocyte antibodies in first attacks of colitis.

BACKGROUND Antineutrophil cytoplasmic antibodies (ANCA) have recently been demonstrated in the sera of patients with inflammatory bowel disease (IBD). METHODS The presence of ANCA was studied in 107 sera obtained during 1 year from 48 patients with a first attack of IBD and in 33 such sera from 19 patients with infectious or infectious-type colitis (non-relapsing colitis (NRC)). RESULTS In 65% (31 of 48) of the IBD patients positive immunofluorescence reactivity against granulocytes was observed, compared with in 5% of the NRC patients. No significant difference in granulocyte reactivity was found either between patients with colonic Crohns disease and those with ulcerative colitis or between active and inactive phases of the disease. Most of the sera showed a perinuclear immunofluorescence staining pattern (68%), in contrast to the classical cytoplasmic staining pattern seen in Wegeners granulomatosis. In sera obtained at the first visit from the 31 IBD patients with positive granulocyte reactivity a hitherto unknown antibody against beta-glucuronidase was found in 42%, whereas in 45% the specificity was not identified. Other antibodies, rarely seen, were directed against myeloperoxidase, lactoferrin, elastase, and cathepsin G. No antibody directed against lysozyme was detected. CONCLUSIONS Positive granulocyte reactivity practically excluded NRC and was seen in more than half of IBD patients. Antibodies against beta-glucuronidase were common, but still almost half of the antibodies remained unknown.

A calorimetric method for continuous recording of lymphocyte proliferation

We have developed a calorimetric technique as an alternative non-radioactive method for measuring mitogen-induced lymphocyte proliferation. Power-time curves can be recorded from as few as 2X10(5) cells suspended in 4 ml medium. This density is, however, too low for the detection of proliferation during a 72 h incubation. Cell numbers exceeding 4X10(6) suspended in 4 ml medium cause pronounced crowding and are therefore too high for use during proliferation studies. We found the optimal initial cell concentration to be 2X10(6) cells suspended in 4 ml of medium. In a four-channel bioactivity monitor, up to four separate incubations can be run in parallel. Furthermore, this method offers the advantage of one-line monitoring of cell proliferation throughout the incubation.

Metabolic Response of Blood Cells to Synthetic Graft-Materials with Special Reference to a Fluoromer Passivated Dacron® Graft. An in Vitro Study Using Microcalorimetry

Microcalorimetry was used to study in vitro the metabolic response from human platelets and leukocytes when incubated with three different synthetic graft-materials. The graft to be studied primarily was Fluoromer Passivated Dacron (FPD) which was compared with ePTFE and with a knitted Teflon graft. A rapid increase in the metabolic activity of platelets was observed, followed by a steady-state for more than one hour, while the platelet metabolism did not differ among the various graft-materials. Leukocytes incubated with FPD showed a high initial metabolism, with a peak after about 15 minutes. After 60 minutes the metabolic response had reached control values. ePTFE and Teflon grafts differed significantly from FPD, without causing any peak metabolic activity. It may be concluded that FPD and ePTFE grafts, as evaluated in vitro, activate platelets to the same extent, while FPD causes a more extensive leukocyte activation. Whether these findings can be interpreted as differences in thrombogenicity and inflammatory responses has not been proven, but seems probable. This in vitro method should make it possible to further study human responses to synthetic materials a method possibly more reliable than animal experiments.