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Biomedical subjects

C G Kallenberg

Publications and source records attributed to C G Kallenberg.

At least 19 recordsLinked to original sources
PubMed1992

Pulmonary function in systemic lupus erythematosus is related to distinct clinical, serologic, and nailfold capillary patterns.

PURPOSE: The purpose of this study was to investigate whether systemic lupus erythematosus (SLE) patients with interstitial lung disease represent a particular subset of patients characterized by the presence of clinical, serologic, and nailfold capillary patterns overlapping scleroderma. PATIENTS AND METHODS: In 57 consecutive patients with SLE, a standardized detailed history was obtained and a physical examination performed, directed at signs and symptoms of connective tissue diseases, in particular scleroderma. Additionally, pulmonary function testing, chest radiography, radionuclide transit studies of the esophagus, nailfold capillary microscopy, and detailed serologic studies directed at the antigenic specificities of antinuclear antibodies were performed. Patients were divided into three groups based on the results of pulmonary function testing, i.e., normal lung function, restriction, or isolated impairment of diffusion. Clinical, serologic, and nailfold capillary microscopic findings were compared among these three groups. RESULTS: Twenty patients had normal lung function, 19 had restrictive lung function loss, and 9 had an isolated impairment of the diffusing capacity (T1,CO). Patients with obstructive lung disease (n = 9) were excluded from analysis. Sclerodermatous changes of the hands were associated with a restrictive lung function pattern. Interstitial changes on chest radiograph were associated with isolated impairment of T1,CO. Nailfold capillary abnormalities correlated with decreased T1,CO and Dm, the component of T1,CO representing the diffusing capacity of the alveolocapillary membrane. Antibodies to U1-RNA were associated with restrictive lung function and decreased T1,CO. CONCLUSION: We conclude that interstitial lung disease is present in a subset of SLE patients characterized by an increased prevalence of scleroderma traits and anti-(U1)RNA antibodies. Microvascular changes may contribute to the development of interstitial lung disease in SLE as well as in scleroderma.

Adult↗
PubMed1992

Antineutrophil cytoplasmic antibodies: a still-growing class of autoantibodies in inflammatory disorders.

Antineutrophil cytoplasmic antibodies (ANCA) have been described as sensitive and specific markers for active Wegener's granulomatosis (WG). ANCA in WG produce a characteristic cytoplasmic staining pattern of neutrophils (c-ANCA) and are directed against proteinase 3 (Pr3), a serine protease from the azurophilic granules. c-ANCA, more or less equivalent to anti-Pr3, occur in more than 90% of patients with extended WG, in 75% of patients with limited WG without renal involvement, and in some 40% to 50% of patients with vasculitic overlap syndromes suggestive of WG such as microscopic polyarteritis. The presence of c-ANCA is highly specific for those diseases (greater than 98%). Changes of levels of c-ANCA precede disease activity and may be used as guidelines for treatment. Antibodies producing a perinuclear staining of ethanol-fixed neutrophils (p-ANCA) occur in a wide range of diseases. They are directed against different cytoplasmic constituents of neutrophils. Among those, antibodies to myeloperoxidase are found in patients with idiopathic crescentic glomerulonephritis, the Churg-Strauss syndrome, polyarteritis nodosa with visceral involvement, and vasculitic overlap syndromes. Their specificity for this group of necrotizing vasculitides is high (94% to 99%), although they may occur in patients with hydralazine-induced glomerulonephritis, anti-glomerular basement membrane disease, and possibly in some patients with idiopathic systemic lupus erythematosus. Antibodies to leukocyte elastase are incidentally found in patients with vasculitic disorders, whereas lactoferrin antibodies are detected in patients with primary sclerosing cholangitis with or without ulcerative colitis and in rheumatoid arthritis. Their diagnostic significance awaits further studies. p-ANCA of undefined specificity may distinguish ulcerative colitis (sensitivity of 75%) from Crohn's disease (sensitivity of 20%). p-ANCA also occur in autoimmune liver diseases: in 75% of patients with chronic active hepatitis, in 60% to 85% of those with primary sclerosing cholangitis, and in about 30% of patients with primary biliary cirrhosis. Finally, p-ANCA are detected in chronic arthritides and in some 5% of healthy controls. Assessment of their diagnostic value has to await further characterization of the antigens involved, allowing the development of antigen-specific assays.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

Influence of ageing on antibody formation in vivo after immunisation with the primary T-cell dependent antigen Helix pomatia haemocyanin.

The in vivo antibody response to the primary T-cell dependent antigen Helix pomatia Haemocyanin (HPH) was studied, in order to detect the possible presence of a humoral immune deficiency in ageing. The IgG subclass distribution of the specific antibodies was also determined. In order to define a dose of HPH which could be used to discriminate between the responsiveness of healthy and immunocompromised individuals, we first established a dose-response curve for this antigen in 60 healthy young volunteers. Their responses were compared with the responses of a group of patients suffering from end stage renal failure. The patients who were treated with haemodialysis showed a significantly lower IgM, IgG and IgA anti-HPH antibody response after immunisation with a dose of 30 micrograms HPH, which could be restored by increasing the antigen dose. Patients treated with continuous ambulant peritoneal dialysis and a group of elderly persons, selected according to the Senieur protocol, showed no impairment of antibody formation after immunisation with 30 micrograms HPH, but in the non-Senieur elderly the anti-HPH antibody response was significantly lower. Furthermore, Senieur and non-Senieur elderly persons showed a diminished IgG2 anti-HPH antibody formation, whereas in the elderly non-Senieur individuals and in the patients with renal insufficiency, IgG1 and IgG3 anti-HPH antibodies were also diminished. This study clearly shows that the so-called age-associated immune deficiency can be the result of disease and is not necessarily due to the ageing process itself.

Adult↗
PubMed1992

Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of disease activity?

To investigate the possible role of IL-6 in the activation of the autoimmune process in systemic lupus erythematosus (SLE), we serially measured concentrations of IL-6, IgG, and anti-dsDNA antibodies before and during exacerbations in patients with SLE. In addition, we serially related the IL-6 response to the generation of the acute phase reactant C-reactive protein (CRP). Sixteen consecutive patients who developed an exacerbation were analysed in this study. Blood samples were drawn in EDTA monthly. At the time of maximal disease activity during exacerbation, IL-6 plasma concentrations were increased (greater than or equal to 6 pg/ml) in 12 out of the 16 cases. Concentrations of IL-6 correlated with the concentrations of CRP (P less than 0.01) and the score of the disease activity index (P less than 0.05). No correlation was found between IL-6 concentrations and concentrations of anti-dsDNA or IgG. The course of changes in IL-6 concentrations before the exacerbation was variable. Five out of the 16 exacerbations studied were characterized by a prominent rise of IL-6 at the time of maximum disease activity. In this subgroup serositis as well as elevated concentrations of CRP were observed more frequently (P less than 0.02). Seven exacerbations were not accompanied or preceded by changes in IL-6 concentrations and showed generally low IL-6 concentrations. In this latter subgroup cerebral involvement was seen more frequently (P less than 0.02). Our data do not suggest a pathogenic role for IL-6 in the generation of IgG and/or anti-dsDNA antibodies before exacerbations. Rises of IL-6 concentrations before exacerbations in SLE seem only to occur in a subgroup of patients with SLE characterized by the presence of serositis and elevated concentrations of CRP during exacerbation.

Adolescent↗
PubMed1992

Treatment of severe thrombocytopenia in systemic lupus erythematosus with intravenous gammaglobulin.

Three patients with lupus with severe auto-immune thrombocytopenia were treated with high doses of intravenous gammaglobulin. In the patient with active disease a prolonged but partial response with respect to platelet counts was observed. In the two other patients who had no disease activity other than thrombocytopenia at the time of intravenous gammaglobulin treatment a minor (and only transient) increase in platelet counts was seen after treatment. No change in the state of disease activity nor in the levels of antinuclear antibodies, circulating immune complexes, nor complement C3/4 was observed in these three patients after treatment with intravenous gammaglobulin.

Adult↗
PubMed1992

Patients with systemic lupus erythematosus and Jaccoud's arthropathy: a clinical subset with an increased C reactive protein response?

Jaccoud's arthropathy is a chronic deforming synovitis occurring in a subset of patients with systemic lupus erythematosus (SLE). To evaluate whether patients with SLE and Jaccoud's arthropathy behave differently in their acute phase reaction from patients with SLE without Jaccoud's arthropathy, a prospective study was carried out on 72 consecutive patients with SLE. Patients were assessed for Jaccoud's arthropathy according to a protocol, disease activity was scored, and laboratory tests, including tests for C reactive protein, were performed. Seven patients were classified as having definite Jaccoud's arthropathy. In those patients the serum concentrations of C reactive protein were higher than in those without Jaccoud's arthropathy, whereas disease activity scores and treatment were comparable. Additionally, patients with Jaccoud's arthropathy had a longer disease duration and a longer history of arthritis than those without, whereas IgM rheumatoid factor was observed more often. The increased concentration of C reactive protein in patients with Jaccoud's arthropathy is compatible with a persistent inflammatory reaction. Serial testing of C reactive protein in combination with other laboratory parameters may be a guideline for treatment in patients with SLE and Jaccoud's arthropathy.

Acute-Phase Reaction↗
PubMed1992

Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions.

Many patients presenting with symptoms suggestive of a connective tissue disease do not fulfill criteria for a specific connective tissue disease at initial presentation. Some of these patients with undifferentiated connective tissue disease eventually develop a specific connective tissue disease. Recently, a large cohort of 213 patients from different centers with undifferentiated connective tissue disease of early onset were enrolled in a prospective protocoled study. Baseline characteristics, including antinuclear antibody profiles, were reported. The aim of this study was to define predictors for the development of specific organ-system involvement and connective tissue diseases in early undifferentiated connective tissue disease. Many patients show overlapping features of two or more connective tissue diseases. The presence of autoantibodies to U1-ribonucleoproteins has been associated with a particular overlap syndrome, mixed connective tissue disease. Most anti-U1-ribonucleoprotein-positive patients with undifferentiated connective tissue disease at presentation appear to develop mixed connective tissue disease over the course of disease. Although levels of anti-U1-ribonucleoprotein do not seem to be related to disease activity, this association suggests a pathogenetic relationship between anti-U1-ribonucleoprotein and mixed connective tissue disease. Genetic studies have shown that patients with antibodies against the 70-kD component of U1-ribonucleoprotein share a common epitope within the groove of their DR molecules at antigen-binding region, pointing to a particular antigen involved in the induction of these antibodies that may be relevant in the etiopathogenesis of associated disease.

Antibodies, Antinuclear↗
PubMed1992

Raynaud's phenomenon as an early sign of connective tissue diseases.

Raynaud's phenomenon (RP) is seen in 5-10% of the population and generally follows an indolent course. In some cases it may be the first sign of a connective tissue disease (CTD). In patients referred to the clinician because of their RP, obviously the more severe cases, CTD, in particular scleroderma, will develop, however, in a considerable percentage. Risk factors for the evolution of CTD are (a) the severity of RP at onset, (b) a positive test for antinuclear antibodies, (c) nailfold capillary abnormalities, and (d) older age at onset. Patients with RP who are at risk for the development of CTD should be followed in order to diagnose (and treat) a developing CTD as early as possible.

Antibodies, Antinuclear↗
PubMed1991

Once daily felodipine in patients with primary Raynaud's phenomenon.

The symptomatic effects of felodipine (Plendil) have been assessed in 10 patients with primary Raynaud's phenomenon in a single blind study. After 2 weeks on placebo, the patients were treated for 6 weeks with felodipine, the dose being titrated stepwise every 2 weeks, starting with 5 mg, and increasing to 10 mg and 20 mg once daily if symptoms persisted. After the drug period the patients received placebo for 2 weeks. Objective measurement by cold exposure finger plethysmography did not show any benefit of felodipine in the higher temperature range, taking 33 degrees C as reference point. However, when using 24 degrees C as the reference point, the area under the plethysmography versus temperature curve (AUC) for 5 mg felodipine were significantly larger than the initial placebo area. The AUC during recovery from cold exposure for the maximal accepted dose of felodipine was significantly larger than for the initial placebo period. Subjective judgement by the patients showed a significant reduction in the number of Raynaud attacks and a trend to a shorter duration of attacks with the maximal dose of felodipine. Two patients became free from attacks of Raynaud's phenomenon. Felodipine 10 mg once daily was well tolerated. It was regarded as the optimal dose to treat patients with Raynaud's symptoms.

Adult↗
PubMed1991

Detection of autoantibodies against myeloid lysosomal enzymes: a useful adjunct to classification of patients with biopsy-proven necrotizing arteritis.

PURPOSE: Assessment of the value of determination of antineutrophil cytoplasmic antibodies (ANCA) and its specificities for classification of patients with biopsy-proven necrotizing arteritis. PATIENTS AND METHODS: The serum samples of 28 consecutive patients with biopsy-proven vasculitis involving medium- and/or small-sized arteries were tested for ANCA by an indirect immunofluorescence technique, by neutrophil extract enzyme-linked immunosorbent assay (ELISA), and by catching ELISA. RESULTS: Eight patients had Churg-Strauss syndrome; six had myeloperoxidase (MPO) antibodies, and in the other two patients, ANCA were not detected. Six patients had polyarteritis nodosa (PAN) limited to the skin and the musculoskeletal system; ANCA were not detected in these patients. Two patients had systemic PAN and both had MPO antibodies. The remaining 12 patients had overlapping clinical features of the different forms of vasculitis. Five patients had polyarteritis in combination with chronic nasal inflammation and glomerulonephritis compatible with Wegener's granulomatosis (WG) but without granulomas in the respiratory tract. All five patients had 29-kd serine protease antibodies. Two patients had polyarteritis in combination with nasal polyposis and asthma compatible with Churg-Strauss syndrome, but eosinophilia was not detected. Both patients had MPO antibodies. Three patients with unclassified granulomatous arteritis had either elastase antibodies or ANCA of unknown specificity. One patient with unclassified systemic vasculitis had 29-kd serine protease antibodies, and one patient with necrotizing arteritis of the bowel in combination with Schönlein-Henoch purpura was negative for ANCA. CONCLUSION: Determination of ANCA and its specificities is a useful adjunct to the classification of patients with biopsy-proven necrotizing arteritis. Within the spectrum of idiopathic vasculitides, 29-kd serine protease antibodies are associated with WG, MPO antibodies are associated with Churg-Strauss syndrome and systemic PAN, and PAN limited to the skin and the musculoskeletal system is not associated with ANCA.

Adult↗
PubMed1991

Rises in anti-double stranded DNA antibody levels prior to exacerbations of systemic lupus erythematosus are not merely due to polyclonal B cell activation.

We investigated whether rises in anti-double stranded DNA (anti-ds DNA) antibody levels prior to disease exacerbations of systemic lupus erythematosus (SLE) are part of a restricted immune response or merely the consequence of polyclonal B cell activation. As possible inducers of polyclonal B cell activation, we analyzed, in addition, the role of clinically apparent infections in relation to changes in levels of anti-ds DNA and disease exacerbations. We prospectively followed 72 lupus patients who were examined for disease activity and infections at least every 3 months by history and physical examination according to a protocol. Once a month, we measured levels of IgG-class antibodies to an unrelated recall antigen (tetanus toxoid), levels of IgG-class antibodies to a viral antigen (cytomegalovirus late antigens [CMV-LA]), levels of total immunoglobulins G and M, and levels of anti-ds DNA (by ELISA and Farr assay). Thirty-three exacerbations and 31 infections were observed during a follow-up period of an average of 18.5 patient months. Twenty-four out of the 27 exacerbations accompanied by a positive test for anti-ds DNA were preceded by a significant rise in anti-ds DNA: in 17 cases by ELISA and in 22 cases by Farr assay. These 24 rises in levels of anti-ds DNA prior to the exacerbation were paralleled by a significant rise in levels of IgG-class anti-tetanus antibodies in 8 cases, anti-CMV-LA antibodies in 9 cases, total IgG in 7 cases, and total IgM in 15 cases. Median rise in anti-ds DNA, as measured both by ELISA and Farr assay, exceeded the median rise in anti-tetanus antibodies, anti-CMV-LA antibodies, and total IgG and IgM (P less than 0.0001). Only one infection was recorded within a period of 3 months prior to an exacerbation, whereas infections never occurred within a period of 3 months prior to a rise in anti-ds DNA. We conclude that rises in anti-ds DNA prior to exacerbations of SLE are largely due to preferential activation of anti-ds DNA-specific B cells and not merely to polyclonal B cell hyperactivity. Clinically significant infections are not related to rises in levels of anti-ds DNA nor to the induction of exacerbations in SLE.

Adolescent↗
PubMed1991

Autoimmunity to lysosomal enzymes: new clues to vasculitis and glomerulonephritis?

The demonstration of autoantibodies to neutrophil cytoplasmic antigens (ANCA) in (1) systemic vasculitides such as Wegener's granulomatosis, classic polyarteritis nodosa and the Churg Strauss syndrome and (2) idiopathic crescentic glomerulonephritis has placed these disorders within the spectrum of autoimmune diseases. The target antigens have been identified as myeloid lysosomal enzymes that are involved in tissue destruction by neutrophils. Recent data suggest a pathogenetic role for these autoimmune responses. The autoantibodies may activate neutrophils, resulting in extensive tissue necrosis. Alternatively, T-cell-mediated immunity to these positively-charged enzymes that localize to polyanionic basement membranes may, in concert with the presence of autoantibodies, result in glomerulonephritis and vasculitis.

Animals↗
PubMed1991

Shifts of anti-Sm-specific antibodies in patients with systemic lupus erythematosus: analysis by counter-immunoelectrophoresis, immunoblotting and RNA-immunoprecipitation.

We investigated serial changes in anti-Sm-specific antibodies by counter-immunoelectrophoresis (CIE), immunoblotting (IB) and RNA-immunoprecipitation (RNA-IP) in three patients with SLE. To assess the immuno-regulatory processes underlying anti-Sm antibody production, we compared changes in anti-Sm-specific antibodies with changes in titres of antinuclear and anti-ds DNA antibodies. IB and RNA-IP detected anti-Sm antibodies earlier than did CIE. The induction of the immune responses against the Sm-specific BB' and D polypeptides occurred separately in two of the three patients. Anti-Sm developed in all three cases after a flare-up of disease, whereas anti-ds DNA antibody levels fluctuated in parallel with disease activity. Thus, anti-Sm and anti-ds DNA antibody production seems to be independently regulated.

Adult↗