Paroxysmal nocturnal haemoglobinuria.
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Biomedical subjects
Publications and source records attributed to T H The.
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Epidermal nuclear Ig deposition (in vivo ANA) was observed in 54 out of 1,717 skin biopsy specimens routinely examined by immunofluorescence. Patterns were speckled (26), homogeneous (24), or nucleolar (3). The speckled pattern was sensitive (94%) but less specific (58%) for mixed connective tissue disease. The homogeneous pattern, found in SLE and scleroderma, was neither sensitive nor specific for those diseases. The nucleolar pattern was infrequently observed in scleroderma. Patterns of in vivo ANA and serum ANA did not correspond in 24% of patients. In vivo ANA were restricted to IgG class; serum ANA in 78% of patients were also of IgM class and in 37% of IgA class. The discrepancies between in vivo and serum ANA suggest that in vivo ANA is a true in vivo phenomenon.
The primary immune response in vivo of 20 patients with selective IgA deficiency was studied and compared to controls. The primary cellular immune response tested by dinitrochlorobenzene (DNCB) was decreased in many patients. The primary humoral immune response was elicited by immunization with the test immunogen Helix pomatia haemocyanin (HPH). Using a direct ELISA technique antibodies against HPH of the IgA, IgG and IgM class were measured. Two weeks after immunization no response of IgA anti-HPH was seen except in three patients who showed a low but detectable antibody level. In spite of normal or even elevated serum IgG and IgM levels there was a significantly lower response of the IgG and IgM anti-HPH antibodies at 2 weeks after immunization as compared to the controls followed by a further decline at 6 weeks. We conclude that selective IgA deficiency is often accompanied by more general disturbances in humoral and cellular immunity to newly encountered antigens.
Circulating immune complexes after a test meal were measured with three methods (PEG precipitation, Clq-ELISA and the indirect granulocyte phagocytosis test) in 10 controls, two symptomless persons with selective IgA deficiency and 14 patients with various types of glomerulonephritis, of which two patients (with idiopathic membranous glomerulopathy and local focal glomerulonephritis) also had selective IgA deficiency. The PEG and Clq-ELISA test did not show significant differences between the groups. In the two symptomless persons with selective IgA deficiency and in the patient with local focal glomerulonephritis and selective IgA deficiency the indirect granulocyte phagocytosis test (IGFT) showed a reproducible increase in IgG, IgM and complement containing immune complexes. In the last patient multiple food antigens were probably responsible for this phenomenon, a rapid amelioration of kidney function could be induced three times by giving an antigen free diet.
This paper describes a modification of the PHA-induced cytotoxicity test of human peripheral blood lymphocytes against a tumour-derived adherent cell line (HeLa), in which the surviving target cells are labelled with [3H]uridine at the end of the assay. There is a direct correlation between [3H]uridine incorporation and the number of adherent target cells. The test proves to be very sensitive at low effector; target cell ratios. Frozen stored cells can be used in this system, a particular advantage because of the possibility of increasing the reproducibility of the assay by using the same batch of cryopreserved lymphocytes as a reference standard in each experiment. PHA-induced cytotoxicity was mainly found in the T cell enriched fraction.
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Antinuclear antibodies (ANA) developed in 13 out of 78 patients treated with captopril for a mean period of 11 months. In another 11 patients, who were ANA-positive before captopril therapy, no increase in ANA titer was observed during treatment. Neither the development nor the presence of ANA before captopril treatment were associated with (drug-induced) lupus erythematosus or increased incidence of clinical side-effects, although development of ANA was accompanied by a serum-sickness-like syndrome in one patient. The ANA were mainly of the IgM class, did not fix complement and were transiently present. In three patients, antinative DNA antibodies, exclusively of IgM class and not complement-fixing, were transiently present without clinical signs of systemic lupus erythematosus, although recurrence of these antibodies was associated with slight proteinuria in one of them.
There was evidence of impaired cellular immunity in 10 patients with myelofibrosis. In-vitro lymphocyte transformation with phytohaemagglutin, concanavalin A, and dinitrochlorobenzene skin reaction were diminished. Signs of impaired humoral activity were also found, the primary response to alpha-Helix pomatia haemocyanin being impaired, particularly in the immunoglobulin-A class. Moreover three patients had a benign paraproteinaemia. Immunecomplexes (IC) could be demonstrated with various test systems. The indirect granulocyte phagocytosis test was positive in 50%, the C1q-binding in 70% and the polyethylene glycol precipitation test in 50%. In most patients complement levels were normal, although the patient with the most advanced disease had low C3A, C3 and C4 levels accompanied by high levels of IC. No correlation could be shown between impaired immune response or levels of IC when they were related to spleen diameter or degree of anaemia. Some relation however existed between disturbed immune response and IC when they were related to time elapsed since diagnosis. It is suggested that the impaired immune response is the result of primary bone marrow disease and that the presence of IC may reflect the extent of fibrosis.
Antinuclear antibodies (ANA) were detected in the sera of 73 out of 138 patients (53%) referred to us because of Raynaud's phenomenon. When ANA were found, systemic manifestations were likely to be present. The use of human fibroblast monolayers as a nuclear substrate allowed differentiation of several fluorescence patterns, including the discrete speckled variety produced by anticentromere antibodies. These antibodies were detected in the sera of 7 out of 10 patients with CRST syndrome (70%), in 7 out of 40 patients with scleroderma (18%), all without kidney-involvement, in one patient with Sjögren's syndrome and severe Raynaud's phenomenon, and in 7 patients with Raynaud's phenomenon associated with a few symptoms of a connective tissue disease (especially scleroderma). ANA testing on tissue culture monolayers in Raynaud's phenomenon appears to be of value in predicting systemic disease manifestations and the presence or possible future development of distinct clinical patterns, especially the CRST syndrome.
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The primary cellular immune responses in multiple sclerosis (MS) patients as compared with healthy controls were investigated with alpha-HPH and DNCB sensitization tests. The results did not reveal significant differences, indicating that no defect or hyperactive state of the cellular immune system is present in MS patients. Some minor and not significant differences between groups of patients or controls could be related to age differences and the degree of invalidism.
Twenty-eight patients with scleroderma were typed for 40 HLA antigens. A highly significant increase in the frequency of HLA-B8 and HLA-DR3 was observed, which was not related to the severity of the disease. In vitro lymphocyte stimulation tests were performed in 26 patients. In addition, humoral and in vitro cellular immune responses to a primary test antigen were measured in 12 of them. Although the group of scleroderma patients as a whole had an impaired cellular response, only the B8/DR3+ patients had a strongly depressed response, whereas the immune response of the others was normal. These findings suggest an association of the haplotype B8/DR3 with impaired cellular immunity.
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Phytohemagglutinin (PHA)-induced or primary cytotoxicity in vitro which is mediated by T lymphocytes, was studied during hepatitis B virus (HBV) infection in 45 hemodialysis patients, and related to liver cell damage and recovery. HBsAg positive patients with raised transaminases had increased primary cytotoxicity similar to nine otherwise healthy subjects with acute hepatitis B. HBsAg positive patients with normal transaminases showed decreased primary cytotoxicity and recovered patients showed normal values. Increased primary cytotoxicity could not be attributed to an increase in T lymphocytes, as all groups of hemodialysis patients had decreased lymphocyte and T-lymphocyte counts without significant differences between them. In the follow-up study none of the 13 HBsAg positive patients with normal transaminases recovered. However, five of the 18 patients with raised transaminases did recover from hepatitis B, accompanied by a decrease in cytotoxicity. These results show that an increased PHA-induced lymphocyte cytotoxicity corresponds with the occurrence of liver cell damage and subsequent recovery in hemodialysis patients with HBV infection. This suggests that cytotoxic T lymphocytes are involved in liver cell damage and recovery in HBV infection.
During the last 3 years plasma exchanges were undertaken in 5 patients with acute Guillain Barré syndrome (G.B.S.). All the patients were admitted in the intensive respiratory care unit and had received six plasma exchange procedures over two weeks (each procedure consists of 2-3 L exchange). The first patient improved dramatically after the second exchange. Moderate success was obtained in two patients. One patient did not show any effect. The fifth patient received plasma exchange one day after her recovery phase had begun but the course of recovery remained uneffected. The effect of plasma exchange was analysed as the patients' response to motor activity, and compared with a historical control group consisting of 50 acute G.B.S. patients admitted in the intensive respiratory care area over the last 25 years. Plasma exchange does not seem to have exerted any significant effect although at any given time the plasma exchange group had higher motor activity than that of the control group. A controlled clinical trial especially in the early phase of the disease is emphasized.
In five patients with paroxysmal nocturnal haemoglobinuria (PNH) immune capacity was tested. We found impaired in-vitro lymphocyte proliferation after stimulation with allogenic lymphocytes and concanavalin A (con A) in different concentrations. This suggests a disturbed T-cell immunity in these patients, although the number of T cells were normal. As the response to phytohaemagglutin (PHA) stimulation was adequate in most patients, it is presumed that a part of the T-cell population remains normal, as is also suggested by a normal in-vivo response to dinitrochlorobenzene (DNCB). Normal immunoglobulin (Ig) levels and normal anti Helix pomatia haemocyanin (HPH) antibody response were found in most patients. Some patients showed a very low response to pokeweed mitogen (PWM), suggesting some disturbance in the B cell capacity. The decreased number of B cells, found in all patients may also be attributed to this dysfunction. Exposure to inulin enhances the in-vitro effect in lymphocytes of patients with PNH. This indicates functional damage in a population of lymphocytes, possibly originating from an abnormal cell clone with the PNH characteristics. It is therefore suggested that the immunological disturbances could be caused by the primary bone marrow disease.
Renal biopsies were performed on 13 patients treated with captopril. In 4 patients findings indicated an early stage of membranous glomerulopathy (MGP). In the other patients electron microscopy showed scanty small subepithelial deposits and immunofluorescence revealed a patchy granular pattern along the glomerular basement membrane. One of the 4 patients with MGP presented with nephrotic syndrome and another with serum-sickness-like syndrome. None of the other patients, including 2 with MGP, had proteinuria or deterioration of renal function. Thus captopril may be associated with the development of immune-complex glomerulopathy.