Erosive polyarthritis as presenting manifestation of Wegener's granulomatosis.
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Arthritis↗
Biomedical subjects
C G Kallenberg
Publications and source records attributed to C G Kallenberg.
Changes in antibodies to C1q predict renal relapses in systemic lupus erythematosus.
The presence of elevated plasma levels of autoantibodies against C1q, a subcomponent of the first component of complement in sera of patients with systemic lupus erythematosus (SLE) has been found to be associated with renal involvement. The purpose of this study was to determine whether increases in anti-C1q antibodies (anti-C1q) precede renal involvement in SLE. Forty-three SLE patients were studied longitudinally to determine the relationship between manifestations of the disease and levels of anti-C1q as well as to identify antibodies against double-stranded DNA (anti-dsDNA). Increased levels of anti-C1q were detected in all 14 of the patients who developed proliferative lupus nephritis out of 17 patients with renal relapses, which was significantly more frequent (P < 0.005) than in patients with nonrenal relapses (six of 16 patients) or with inactive disease (two of 10 patients). Increased anti-dsDNA levels were observed in 14 of 17 patients with renal relapses compared with 15 of 16 patients with nonrenal relapses and five of 10 patients with inactive disease. Significant increases in anti-C1q levels prior to the relapse occurred in 10 of 14 patients who developed proliferative nephritis and in three of 16 patients with nonrenal relapses. Significant increases in anti-dsDNA levels occurred in 11 patients of the former group and in nine patients of the latter group. No significant increases in anti-C1q or anti-dsDNA levels were observed in the patients with inactive disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Host-microflora interaction in systemic lupus erythematosus (SLE): circulating antibodies to the indigenous bacteria of the intestinal tract.
Experimental data suggest a role for the microflora in the disease expression of systemic lupus erythematosus (SLE). In active SLE anti-ds-DNA antibodies are supposed to be pathogenic by forming immune complexes with DNA. Bacteria might induce the production of anti-ds-DNA antibodies. To explore the relation between the host and his microflora in SLE in comparison with healthy controls we studied the prevalence of systemic antibodies to faecal bacteria that were discriminated by their morphology by indirect immunofluorescence. IgM titres against their own faecal microflora were found to be lower both in active and inactive SLE when compared to healthy individuals. IgG-class antibacterial antibodies were increased in inactive SLE but decreased in active SLE compared to inactive SLE and healthy controls, although plasma levels of total IgG were almost doubled in active SLE. The lower IgG antibacterial antibody titres in active SLE might possibly result from sequestration of these IgG antibodies in immune complexes, indicating a possible role for antibacterial antibodies in exacerbations of SLE.
Adolescent↗
Renal ischemia/reperfusion injury contributes to renal damage in experimental anti-myeloperoxidase-associated proliferative glomerulonephritis.
The occurrence of focal fibrinoid necrosis of capillary loops in the very early stages of ANCA-associated necrotizing crescentic glomerulonephritis (NCGN) and the increased prevalence of this disease at older age suggest that renal ischemia may play an additional role in its pathophysiology. In the present study we investigated the contribution of renal ischemia to the induction of anti-myeloperoxidase (MPO) associated NCGN in a previously described rat model of this disease. The development of renal lesions is dependent on the presence of an anti-MPO immune response and the localization of a lysosomal extract containing lytic enzymes and MPO in combination with hydrogen peroxide (H2O2) along the glomerular basement membrane (GBM). The hypothesis tested whether perfusion of hydrogen peroxide (H2O2) could be replaced by ischemia/reperfusion (I/R) injury, as I/R injury activates endothelial cells to produce oxygen metabolites. I/R was induced by clamping the renal artery for 20 minutes in kidneys in which the circulation had been restored several minutes after perfusion with the lysosomal extract in MPO immunized rats. Rats developed lesions characterized by intra- and extracapillary cell proliferation, periglomerular infiltration, ruptures in Bowman's capsule, ischemic tubuli, and interstitial mononuclear infiltrate. Immune deposits, however, persisted for a longer time along the GBM after perfusion of lytic enzymes followed by I/R injury compared to previous studies in which H2O2 in conjunction with lytic enzymes were perfused in MPO-immunized rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Decreased frequency of HLA-DR13DR6 in Wegener's granulomatosis.
The pathogenesis of Wegener's granulomatosis, microscopic polyangiitis and idiopathic rapidly progressive glomerulonephritis (RPGN) is still unclear; in vitro data support both humoral and cellular autoimmune mechanisms. An association of Wegener's granulomatosis with HLA antigens has been described, with conflicting results concerning the antigens involved. We have performed serological HLA typing of patients at two different laboratories within the Netherlands (N = 118 and N = 106,N respectively). A significant decrease in the frequency of HLA-DR13DR6 was present in both patient groups in comparison to controls (chi 2 = 21.9; corrected P value < 0.004 for both groups together). There were no differences in the distribution of HLA-antigens between patients with Wegener's granulomatosis and microscopic polyangiitis, between cANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) and pANCA (perinuclear ANCA, anti-MPO) positive patients, and between patients with and without relapsing disease.
Aged↗
Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions.
Connective tissue diseases (CTDs) frequently present with one or only a few symptoms, which does not allow prompt diagnosis. Raynaud's phenomenon is one of those symptoms. However, only a minority of patients who present with Raynaud's phenomenon develop a CTD. Prognostic factors for the future development of CTD in such patients are older age at presentation, more severe Raynaud's phenomenon, the presence of antinuclear antibodies, and abnormal patterns on nailfold capillary microscopy. Some patients have overlapping symptoms of various CTDs. Mixed connective tissue disease (MCTD) is the prototype of such an overlapping syndrome. However, during follow-up, most patients with MCTD develop a specific CTD, either scleroderma, systemic lupus erythematosus, rheumatoid arthritis, or combinations of those illnesses. Primary pulmonary hypertension is one of the leading causes of death in MCTD. Its treatment is insufficient, although continuous prostacyclin infusion may provide some relief. New therapies such as nitric oxide and combined heart-lung transplantation in an early stage should be explored. The autoimmune response to small nuclear ribonucleoproteins, which is highly characteristic for MCTD, interestingly shows cross-reactivity with retroviral antigens, and the cooccurrence of human T cell lymphotropic virus type I and HIV infection with MCTD has been reported. This suggests that those viruses, possibly by molecular mimicry, play a role in the induction of the disease. Fibrotic conditions related to silicone exposure still evoke much interest. However, most recent data do not substantiate a role for silicone gel breast implants in the development of autoimmune CTDs.
Connective Tissue Diseases↗
ANCA--pathophysiology revisited.
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Antibodies, Antineutrophil Cytoplasmic↗
Activation of granulocytes by anti-neutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis: a predominant role for the IgG3 subclass of ANCA.
To study ANCA-induced granulocyte activation in relation to disease activity in Wegener's granulomatosis (WG), serum samples taken from patients with WG at the time of active (n = 17) and inactive (n = 17) disease were analysed for their capacity to activate primed normal donor granulocytes. Compared with control sera (n = 6), the capacity of IgG fractions from patients with WG to induce the respiratory burst was significantly higher (P < 0.0001). Furthermore, the capacity to induce the respiratory burst significantly correlated with ANCA titre (r = 0.499, P = 0.003). IgG fractions from patients with active extensive disease induced the respiratory burst significantly more strongly than IgG fractions from patients with limited disease (n = 7) (P < 0.01) or patients during disease remission (n = 17) (P < 0.001). As ANCA-induced neutrophil activation is Fc-dependent and different IgG subclasses are involved in the interaction with various Fc receptors from neutrophils, we assessed changes in ANCA titre, total IgG and IgG subclass distribution of ANCA during active disease and remission in relation to the neutrophil-activating capacity of ANCA. Changes in capacity to activate granulocytes were related neither to changes in titre nor to changes in levels of total IgG, IgG1, IgG3, or IgG4 subclass of ANCA. However, changes in capacity to induce the respiratory burst were significantly related to changes in the relative amount of the IgG3 subclass of ANCA (P < 0.001), and not to changes in the relative amount of IgG1 or IgG4 subclass of ANCA. These data suggest that the increase in neutrophil-activating capacity of ANCA from inactive to active disease is, at least in part, based on the relative increase of the IgG3 subclass of ANCA that occurs during active disease.
Adult↗
Serological markers of disease activity in systemic lupus erythematosus.
When measured serially by Farr assay at a frequency of approximately once a month, changes in levels of anti-dsDNA appear to be a good predictor of clinical disease activity. Although the role of antibodies to the RNA component of snRNP awaits further studies, measurement of anti-UsnRNP antibody levels seems to be of limited value in monitoring lupus patients in clinical practice. The same holds for antibodies to SSA (Ro) and anti-histone antibodies. More recently described antibodies to C1q are probably useful in the follow-up of SLE patients suspected of proliferative renal involvement. The best alternative to measuring levels of the antibodies mentioned before is probably serial analysis of activation of the complement cascade. Levels of complement factors like C3, C4 and, functionally, CH50 remain a useful parameter for monitoring disease activity in SLE, although fluctuations in anti-dsDNA as measured by Farr assay seem superior with respect to sensitivity and specificity for an ensuing relapse. Despite the problems in sampling, measuring levels of activated split products of complement factors like C3a, C3d or C5a may prove to be a valuable tool in the follow-up of lupus patients. The involvement of the endothelial surface is illustrated by rising sVCAM-1 levels prior to relapses in SLE. Although one could expect that subsequent inflammation should be reflected by increased levels of inflammatory molecules like CRP and IL-6, the use of these molecules as predictors of lupus activity seems limited. Interferon-alpha as a direct reflector of the effector phase seems, however, rather promising in this respect and awaits longitudinal studies to analyse the possible relation with clinical disease activity and other serological parameters.
Antibodies, Antinuclear↗
Renal disease--another effect of silica exposure?
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Granulomatosis with Polyangiitis↗
Esophageal hypomotility in primary and secondary Raynaud's phenomenon: comparison of esophageal scintigraphy with manometry.
UNLABELLED: Esophageal motility was assessed by manometry and scintigraphy in 25 patients with primary Raynaud's phenomenon and 24 patients with secondary Raynaud's phenomenon as part of a connective tissue disorder. METHODS: For each scintigraphic study, transit time was evaluated after three separate swallows. Scintigraphy was abnormal if transit time was longer than 15 sec for two or three measurements. RESULTS: In the case of primary Raynaud's phenomenon, manometry was normal in 24 of 25 patients. A similar ratio was found with scintigraphy. In the case of secondary Raynaud's phenomenon manometry was abnormal in 15 of 24 patients, while scintigraphy was abnormal in 13 of 24 patients. Considering manometry as gold standard, overall sensitivity of scintigraphy was 86%, specificity 89%, positive predictive value 75% and negative predictive value 94%. CONCLUSION: Esophageal dysfunction is common in patients with connective tissue disorders but rare in patients with primary Raynaud's phenomenon. Esophageal scintigraphy is a useful noninvasive initial screening test for esophageal dysfunction in patients with Raynaud's phenomenon.
Adolescent↗
Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis.
OBJECTIVE: To examine possible risk factors for relapse, including chronic nasal carriage of Staphylococcus aureus and serial antineutrophil cytoplasmic antibody (ANCA) determinations in patients with Wegener granulomatosis. DESIGN: Observational cohort study. SETTING: Outpatient clinic at a university-affiliated hospital. PATIENTS: Consecutive patients (n = 71) with biopsy-proven Wegener granulomatosis who were seen during follow-up at the outpatient clinic from January 1988 to July 1991. Fourteen patients were ineligible or dropped out; 57 patients were analyzed. MEASUREMENTS: Serial ANCA determinations and swab cultures of both anterior nares for S. aureus taken at each visit every 4 to 6 weeks. Occurrence of infections and relapses of Wegener granulomatosis were identified according to strict, predefined criteria. RESULTS: Thirty-six of the 57 patients (63%; 95% CI, 49% to 76%) were found to be chronic nasal carriers of S. aureus (> or = 75% of nasal cultures positive for S. aureus). Proportional-hazards regression analysis identified chronic nasal carriage of S. aureus (adjusted relative risk, 7.16; CI, 1.63 to 31.50), creatinine clearance above 60 mL.min-1 (adjusted relative risk, 2.94; CI, 1.27 to 6.67), and a history of previous relapses of Wegener granulomatosis (adjusted relative risk, 1.33; CI, 0.98 to 1.78) as independent risk factors for relapse. Twenty-two of 33 patients persistently or intermittently positive for ANCA had a relapse as opposed to only 1 of 21 persistently negative patients. Relapses of Wegener granulomatosis were not related to diagnosed infections. CONCLUSION: Chronic nasal carriage of S. aureus identifies a subgroup of patients with Wegener granulomatosis who are more prone to relapses of the disease, suggesting a role for S. aureus in its pathophysiology and a possible clue for treatment.
Adult↗
Nomenclature of systemic vasculitides. Proposal of an international consensus conference.
The following are some of the conclusions and proposals made at the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis. 1. Although not a prerequisite component of the definitions, patient age is recognized as a useful discriminator between Takayasu arteritis and giant cell (temporal) arteritis. 2. The name "polyarteritis nodosa," or alternatively, the name "classic polyarteritis nodosa," is restricted to disease in which there is arteritis in medium-sized and small arteries without involvement of smaller vessels. Therefore, patients with vasculitis affecting arterioles, venules, or capillaries, including glomerular capillaries (i.e., with glomerulonephritis), are excluded from this diagnostic category. 3. The name "Wegener's granulomatosis" is restricted to patients with granulomatous inflammation. Patients with exclusively nongranulomatous small vessel vasculitis involving the upper or lower respiratory tract (e.g., alveolar capillaritis) fall into the category of microscopic polyangiitis (microscopic polyarteritis). 4. The term "hypersensitivity vasculitis" is not used. Most patients who would have been given this diagnosis fall into the category of microscopic polyangiitis (microscopic polyarteritis) or cutaneous leukocytoclastic angiitis. 5. The name "microscopic polyangiitis," or alternatively, "microscopic polyarteritis," connotes pauci-immune (i.e., few or no immune deposits) necrotizing vasculitis affecting small vessels, with or without involvement of medium-sized arteries. Cryoglobulinemic vasculitis, Henoch-Schönlein purpura, and other forms of immune complex-mediated small vessel vasculitis must be ruled out to make this diagnosis. 6. The name "cutaneous leukocytoclastic angiitis" is restricted to vasculitis in the skin without involvement of vessels in any other organ. 7. Mucocutaneous lymph node syndrome must be present to make a diagnosis of Kawasaki disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies, Antineutrophil Cytoplasmic↗
Relationship between antineutrophil cytoplasmic antibody levels and disease activity in Wegener's granulomatosis: comment on the article by Kerr et al.
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Antibodies, Antineutrophil Cytoplasmic↗
Serum levels of soluble adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin in patients with Wegener's granulomatosis. Relationship to disease activity and relevance during followup.
OBJECTIVE: To assess the value of measuring serum levels of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAMP-1), and soluble E-selectin for monitoring disease activity in Wegener's granulomatosis (WG). METHODS: A sandwich enzyme-linked immunosorbent assay was used to measure levels of soluble adhesion molecules at the time of diagnosis in 22 consecutive patients with WG, in 12 WG patients studied serially prior to disease relapse, at the time of upper airways infection in 18 patients with inactive WG, and in 57 controls. Disease activity was assessed by disease activity score and C-reactive protein levels. RESULTS: At diagnosis of WG, sICAM-1 and sVCAM-1 levels were significantly elevated and correlated with disease activity. At the time of relapse, a significant increase in all 3 soluble adhesion molecules was found compared with levels at 6 months prior to relapse, but only sVCAM-1 levels were significantly elevated compared with those in controls. Levels of soluble adhesion molecules at the time of relapse did not differ from those measured during an upper airways infection without disease activity. CONCLUSION: Elevated serum levels of sICAM-1 and sVCAM-1 can be found in active WG and correlate with disease activity. However, their clinical relevance for followup is limited due to lack of sensitivity and specificity for WG disease activity.
Adolescent↗
Successful outcome of pregnancy after treatment of maternal anti-Ro (SSA) antibodies with immunosuppressive therapy and plasmapheresis.
In this short communication we describe a patient with anti-SSA and anti-SSB antibodies whose first child died of congenital complete heart block (CCHB). During her second pregnancy she was treated with prednisolone, azathioprine, and plasmapheresis, and levels of anti-SSA and anti-SSB antibodies fell significantly. The pregnancy evolved uneventfully and resulted in the birth of an unaffected male infant. This is the fourth reported case of a successful outcome of pregnancy after treatment with immunosuppressive drugs in a woman with a significant risk of recurrence of CCHB.
Adult↗
Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with inflammatory bowel disease (IBD). Relation to disease pattern and disease activity.
Anti-neutrophil cytoplasmic antibodies producing a perinuclear fluorescence pattern on ethanol-fixed granulocytes (p-ANCA) were found in 33 of 67 patients (49%) with ulcerative colitis (UC) but also in 14 of 35 patients (40%) with Crohn's disease (CD). In the latter condition p-ANCA were equally present in subgroups with colonic, ileocolonic, or ileal involvement only. Titers of p-ANCA were higher in patients with UC compared to CD patients, in particular when comparing patients with active disease. In contrast to findings in CD, patients with active UC had higher titers of p-ANCA than patients with inactive UC. Although p-ANCA were incidentally directed to lactoferrin, both in UC and CD, and to proteinase-3 and myeloperoxidase in UC only, the antigenic nature of p-ANCA could not be identified in most of the cases. We conclude that, within the spectrum of inflammatory bowel disease, the presence of p-ANCA is not specific for UC. When titers of p-ANCA are taken into account, the presence of high-titered p-ANCA, however, suggests active UC.
Adolescent↗