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Biomedical subjects

C G Kallenberg

Publications and source records attributed to C G Kallenberg.

At least 181 records · Page 10Linked to original sources
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↗
PubMed1991

Predominance of IgG1 and IgG4 subclasses of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener's granulomatosis and clinically related disorders.

In view of the supposed hypersensitivity, the elevated levels of IgE, and the occurrence of eosinophilia reported in Wegener's granulomatosis and related conditions, we studied the IgG subclass distribution of ANCA directed against a 29-kD serine protease and myeloperoxidase (MPO) in 41 untreated ANCA-positive patients with several forms of active vasculitis and/or glomerulonephritis. We found that both 29-kD ANCA and MPO ANCA were predominantly of the IgG1 and IgG4 subclass in all groups of patients. The additional presence of IgG3 subclass was associated with renal involvement. We compared the subclass distribution of ANCA with that of total IgG subclass levels, and with the IgG subclass distribution of antibodies to cytomegalovirus (CMV) as a persistent endogenous antigen and antibodies to tetanus toxoid (TT) as an exogenous recall antigen. Total levels of IgG4 were elevated in the majority of the patients together with elevated IgG1 levels. Antibodies to CMV and TT, however, had the same subclass distribution as found in normals and did not show enhanced IgG4 expression. ANCA belong predominantly to the IgG1 and IgG4 subclass, which may suggest that the production of ANCA is related to recurrent exposition to the antigen(s) involved, possibly as part of a hypersensitivity reaction.

Adult↗
PubMed1991

Transient arthritis with positive tests for rheumatoid factor as presenting sign of shunt nephritis.

Shunt nephritis is a rare complication of a chronically infected ventriculoatrial shunt. A 17 year old boy is described, with arthritis in both ankles and positive rheumatoid factor tests, who presented with symptoms of shunt nephritis. Blood cultures were positive for Staphylococcus epidermidis. The patient recovered completely after removal of the shunt and antibiotic treatment. Shunt nephritis should be considered in patients with a ventriculoatrial shunt presenting with arthritis, and the arthritis may be an early indicator of an infected ventriculoatrial shunt.

Adolescent↗
PubMed1991

Tubular dysfunction in proliferative lupus nephritis.

We prospectively studied renal tubular function during 11 consecutive exacerbations of proliferative glomerulonephritis in 8 patients with systemic lupus erythematosus (SLE). We found a rise in the fractional excretion of beta 2-microglobulin (p less than or equal to 0.05) and dimercaptosuccinic acid (DMSA; p less than or equal to 0.02) during the exacerbations. These changes coincided with a fall in the glomerular filtration rate (p less than or equal to 0.02). Since fractional excretion of beta 2-microglobulin and DMSA can be considered as markers for tubular function, their rise during exacerbation and their fall (p less than or equal to 0.01) to control values during remission indicate that tubular dysfunction frequently occurs during active proliferative glomerulonephritis in SLE and can be influenced by immunosuppressive treatment. As no correlation was found between the different tubular function studies and the activity index of tubulointerstitial abnormalities in the renal biopsy, it is suggested that tubular function studies are probably a more sensitive indicator of tubulointerstitial disease than this activity index.

Adolescent↗
PubMed1991

Changes in levels of antibodies against the 70 kDa and a polypeptides of the U1RNP complex in relation to exacerbations of systemic lupus erythematosus.

In order to investigate whether disease exacerbations of systemic lupus erythematosus (SLE) are accompanied or preceded by changes in antibody levels against the U1RNA associated 70 kDa and A polypeptides, we prospectively collected plasma specimens from 71 patients with SLE. We compared changes in anti-70 kDa/anti-A levels, measured by ELISA using cloned antigens, with changes in levels of anti-dsDNA and total IgG. Measurable levels of anti-70 kDa (n = 10) and/or anti-A antibodies (n = 6) were detected during 10 exacerbations. Four of the 10 exacerbations with a measurable level of anti-70 kDa antibodies were preceded by a significant rise in anti-70 kDa levels, 2 by a significant fall, while levels of anti-70 kDa did not change in the remaining 4 cases. Only one of the 6 exacerbations with detectable anti-A antibody levels was preceded by a significant rise in anti-A antibodies, while levels did not change before exacerbation in the other 5 cases. Six of the 10 exacerbations were preceded by a significant rise in anti-dsDNA; in 4 cases levels of anti-dsDNA did not change before exacerbation. In contrast to anti-dsDNA, no relation was found between changes in levels of anti-70 kDa/anti-A and changes in disease activity. Significant changes in levels of anti-70 kDa/anti-A, occurring in 6 cases, were accompanied by parallel changes in total IgG in 5 of these 6. We conclude that, in contrast to anti-dsDNA, serial measurement of levels of anti-70 kDa/anti-A is not useful for monitoring disease activity or predicting disease exacerbations in SLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre.

58 patients with biopsy-proven Wegener's granulomatosis (WG) were prospectively screened for clinical evidence of the disease 3-monthly, with antineutrophil cytoplasmic antibody (ANCA) measurements every month. Over 24 months, ANCA rose in 20 patients, 9 of whom were randomly assigned to receive combined 9 and 3 month courses of cyclophosphamide and prednisolone, respectively, at the time of ANCA rise; and 11 patients who were untreated except if there was a clinical relapse. 6 of 11 untreated patients relapsed within 3 months of ANCA rise. 3 of the remaining 5 patients relapsed after 3 months. There were no early or late relapses in patients randomised to treatment. Patients receiving no treatment at the time of ANCA rise took more cyclophosphamide and prednisolone than patients who were treated. Side-effects did not significantly differ between the two groups.

Adult↗
PubMed1990

Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. A long-term, prospective study.

To evaluate the predictive power of changes in levels of antibodies to double-stranded DNA (anti-dsDNA) as a predictor of disease exacerbations in systemic lupus erythematosus (SLE), we performed a prospective study on 72 unselected patients with SLE (mean duration of study 18.5 months, range 6-35 months). Patients were seen at least once every 3 months, and disease activity was scored according to a specific protocol. Plasma samples were obtained at least once every month and were assessed for anti-dsDNA antibody (by the Crithidia luciliae assay, an enzyme-linked immunosorbent assay [ELISA], and the Farr assay) and for complement components C3 and C4. Twenty-seven of 33 disease exacerbations observed during the study period were accompanied by a positive test result for anti-dsDNA antibody (27 by the Farr assay, 19 by the C luciliae assay, and 23 by the ELISA). Twenty-four of these exacerbations were preceded by a significant increase in anti-dsDNA antibody levels (23 by the Farr assay, 12 by the C luciliae assay, and 17 by the ELISA). The first observance of a significant increase in anti-dsDNA antibody levels preceded the exacerbation by 8-10 weeks. Significant increases in anti-dsDNA antibody levels not followed by an exacerbation were observed in 5 cases by the Farr assay, in 7 cases by the C luciliae assay, and in 3 cases by the ELISA; however, in 3 cases, 2 cases, and 1 case, respectively, these increases were followed by an increase in disease activity that did not fulfill the criteria for an exacerbation. Serial measurement of anti-dsDNA antibody levels was more sensitive for predicting exacerbations than was measurement of C3 and/or C4 levels (P less than 0.03). Serial assessment of anti-dsDNA antibody levels, especially by the Farr assay, is a sensitive and reasonably specific method for predicting disease exacerbations in SLE.

Adolescent↗
PubMed1990

Pulmonary diffusing capacity disturbances are related to nailfold capillary changes in patients with Raynaud's phenomenon with and without an underlying connective tissue disease.

PURPOSE: The aim of this study was to evaluate whether pulmonary microvascular damage is part of a more generalized involvement of the microvasculature in the spectrum of scleroderma (Scl)-like syndromes. PATIENTS AND METHODS: We studied four groups of patients, all with Raynaud's phenomenon (RP), distinguished by the extent and nature of their underlying connective tissue disease. Twenty-two patients had primary RP (pRP), another 22 patients had RP and an undifferentiated connective tissue disease (uCTD), 15 patients had Scl, and eight patients had the CREST syndrome (CREST). Pulmonary vascular damage in these groups was assessed by measuring the pulmonary diffusing capacity (T1,CO) and its components: the diffusing capacity of the alveolocapillary membrane (Dm) and the pulmonary capillary blood volume (Vc). Results were compared with morphologic abnormalities of the nailfold capillaries, as determined by nailfold capillary microscopy, and related to the presence of antinuclear antibodies. RESULTS: Vc was below normal in 38% and 43% of patients with pRP and uCTD, respectively (versus 52% in patients with Scl or CREST combined). In contrast, Dm was below normal in only 5% and 26% of patients with pRP and uCTD, respectively (versus 61% in patients with Scl or CREST combined). In patients with Scl and CREST, Dm was significantly decreased as compared with the former groups (p less than 0.01). Dm was also the pulmonary function parameter that correlated most strongly with both nailfold capillary abnormalities and the presence of antinuclear antibodies, whereas Vc did not. CONCLUSION: Early pulmonary involvement in Scl syndromes is functionally characterized by a lowered Dm, correlating with morphologic changes of the nailfold capillaries. Decreased Vc is probably a reflection of RP of the pulmonary vasculature.

Adult↗
PubMed1990

Clinical associations of antiribonucleoprotein antibodies in patients with systemic lupus erythematosus.

The authors undertook a cross-sectional study to investigate the clinical associations of antiribonucleoprotein (anti-RNP) antibodies in 49 patients with systemic lupus erythematosus (SLE) without other concomitant connective tissue disorders. The traditional counterimmunoelectrophoresis (CIE) and the immunoblotting (IB) technique were compared. Clinically, special attention was given to the identification of sclerodermalike features. All patients completed a detailed questionnaire, physical examination, and additional investigations including pulmonary function tests, chest roentgenogram, radionuclide transit studies of the esophagus, and nailfold capillary microscopy. Pulmonary function testing and radionuclide transit studies of the esophagus were very sensitive for the detection of (subclinical) pulmonary and esophageal involvement, respectively. Within the relatively homogeneous SLE population, a subset was recognized that was characterized clinically by the presence of sclerodermalike features such as Raynaud's phenomenon, sclerodactyly, interstitial changes on chest roentgenogram, and decreased numbers of nailfold capillary loops, and serologically by the presence of anti-RNP antibodies. IB was somewhat more sensitive than CIE for the detection of anti-RNP (anti-Sm/anti-nRNP) antibodies but did not identify other clinical associations. Thus, anti-RNP antibodies in SLE are associated with scleroderma-associated features. For clinical practice, CIE is the technique recommended for their detection.

Adolescent↗
PubMed1990

Autoantibodies against myeloid lysosomal enzymes in crescentic glomerulonephritis.

To investigate the possible association of crescentic glomerulonephritis (CGN) with autoantibodies to myeloid lysosomal enzymes, we tested sera from 35 consecutive patients with CGN without diagnostic immunohistological findings in their renal biopsy for the presence of antineutrophil cytoplasmic antibodies directed against a 29 kD antigen from azurophilic granules (29 kD-ANCA), against myeloperoxidase (MPO-ANCA) and against elastase (elastase-ANCA), using antigen-catching ELISAs with well-defined monoclonal antibodies. 29 kD-ANCA were present in the sera of all nine patients with CGN as part of biopsy-proven Wegner's granulomatosis (WG), of ten patients with CGN and clinically suspected WG, and of two patients with idiopathic CGN. Sera from the remaining patients with clinically suspected WG (N = 5) or idiopathic CGN (N = 6) were negative for 29 kD-ANCA, but invariably positive for MPO-ANCA. Neither of these antibodies could be detected in sera from patients with CGN of infectious origin (N = 3), different forms of CGN (N = 7), other renal lesions (N = 34), or normal controls (N = 52). None of the sera tested were positive for elastase-ANCA. Our results indicate that both vasculitis-associated CGN and idiopathic CGN are associated with autoantibodies against myeloid lysosomal enzymes. This finding places these disorders within one spectrum of diseases.

Autoantibodies↗
PubMed1990

Changes in plasma levels of interleukin-2 receptor in relation to disease exacerbations and levels of anti-dsDNA and complement in systemic lupus erythematosus.

Interleukin-2 receptor (IL-2R) is expressed and released predominantly by activated T cells. In order to investigate whether disease exacerbations of systemic lupus erythematosus (SLE) are preceded by T cell activation, we prospectively measured levels of IL-2R once a month, from 6 months prior to exacerbations until 1 month afterwards. To assess the temporal relation between T cell activation and B cell activation, we measured, in addition, levels of anti-dsDNA, complement C3/C4, and total IgG. During a mean follow-up period of 23 months, 40 exacerbations occurred in 21 out of the 71 participating patients. For the present study one exacerbation per patient was evaluated. During exacerbation levels of IL-2R were increased in 18 out of the 21 cases and correlated with levels of anti-dsDNA (P less than 0.02), C3 (P less than 0.02), and C4 (P less than 0.01), but not with the score of the disease activity index. Levels of IL-2R rose prior to the exacerbation (P less than 0.02) and fell afterwards following treatment (P less than 0.05). Even in the absence of disease activity or during minor disease symptoms IL-2R levels were higher (P less than 0.01) than in healthy controls. Sixteen out of the 21 exacerbations (76%) were preceded by a significant increase in IL-2R. Changes in levels of anti-dsDNA and complement C3/C4 tended to precede changes in levels of IL-2R. We conclude that increased levels of IL-2R, compatible with T cell activation, are present in SLE already during inactive disease. These levels further increased prior to exacerbations of disease. As such, IL-2R is an indicator of disease activity in SLE. Serial measurement of IL-2R is a sensitive test for predicting disease exacerbations of SLE.

Adolescent↗