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C G Kallenberg

Publications and source records attributed to C G Kallenberg.

At least 37 records · Page 2Linked to original sources
PubMed2001

Elevated D8/17 expression on B lymphocytes, a marker of rheumatic fever, measured with flow cytometry in tic disorder patients.

OBJECTIVE: Elevated D8/17 expression on B lymphocytes is a known susceptibility marker of rheumatic fever. Previous studies have reported higher than usual D8/17 expression on B lymphocytes of patients with tic disorders. The purpose of this study was to assess D8/17 expression on B lymphocytes of tic disorder patients by using an objective method in which no operator variability was involved. METHOD: D8/17 expression on B lymphocytes was assessed with flow cytometry by using an immunoglobulin M (IgM) monoclonal D8/17-specific antibody in an unselected group of Dutch patients with tic disorders (N=33) and healthy volunteers (N=20). Binding of this monoclonal antibody was compared with binding of an irrelevant IgM monoclonal antibody, and the shift in mean fluorescence intensity of the D8/17-specific antibody compared to that of the irrelevant IgM monoclonal antibody was used as a measure of D8/17 overexpression. For the patients, Yale Global Tic Severity Scale scores were used to assess disease severity. RESULTS: D8/17 overexpression in the patient group (mean=16.8 arbitrary units, SD=30.5) was significantly higher than in the comparison group (mean=3.2, SD=3.0). A significant minority of the patients (N=13, 39.4%), however, had levels of D8/17 overexpression within the range of that of the healthy comparison subjects. Flow cytometric analysis did not indicate a separate subpopulation of D8/17-positive B cells. CONCLUSIONS: These data confirm the utility of D8/17 B cell overexpression as a peripheral blood marker in patients with tic disorders and are compatible with a streptococcus-related pathogenesis for at least a subgroup of patients with tic disorders.

Adolescent↗
PubMed2001

Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE): relation to lymphocyte activation and disease activity.

Levels of apoptotic lymphocytes have been found to be increased in SLE and persistence of apoptotic cells has been associated with autoantibody production. Increased lymphocyte Fas (CD95) expression due to lymphocyte activation may account for increased susceptibility to Fas-mediated apoptosis in SLE. Flowcytometry was performed to evaluate membrane expression of Fas in combination with the activation markers CD25, HLA-DR and CD38 on, respectively, CD4+, CD8+ and CD19+ lymphocytes of SLE patients with inactive (n = 20) and with active disease (n = 13). SLEDAI-scores were calculated. Healthy volunteers (n = 14) served as controls. Percentages of CD4+ T-cells expressing CD25 and CD19+ B-cells expressing CD38 were increased in patients with active disease compared to controls (P = 0.03, P = 0.04, respectively). In contrast to CD4+ and CD8+ cells, percentages of CD19+ cells expressing Fas were increased in SLE patients with active disease (P = 0.0002 vs controls). In these patients percentages of cells double positive for both CD38 and Fas were increased compared to patients with inactive disease (P = 0.006) and controls (P = 0.0007). Percentages of CD19+ cells expressing Fas correlated with SLEDAI-scores. In SLE patients, percentages of Fas-expressing B-lymphocytes are increased, are related to the state of lymphocyte activation, and correlate to disease activity. Increased Fas expression results in a higher susceptibility for Fas-mediated apoptosis, which might contribute to the increased levels of apoptotic lymphocytes in SLE patients.

Adult↗
PubMed2001

Proteinase 3, Wegener's autoantigen: from gene to antigen.

Proteinase 3 (PR3) is one of four serine protease homologues in the azurophilic granules of neutrophils and granules of monocytes. It is of importance that anti-neutrophil cytoplasmic antibodies (ANCA) in patients with Wegener's granulomatosis (WG) are mainly directed against PR3 only. Furthermore, PR3 is overexpressed in a variety of acute and chronic myeloid leukemia cells. Cytotoxic T lymphocytes specific for a PR3-derived peptide have been shown to specifically lyse leukemia cells that overexpress PR3. This review will focus on PR3 and the characteristics of PR3 that might implicate this particular antigen in the pathogenesis of WG and as target for immunotherapy in myeloid leukemias. We will discuss the genetic localization and gene regulation of PR3, the processing, storage, and expression of the PR3 protein, and the physiological functions of PR3, and compare this with the three other neutrophil-derived serine proteases: human leukocyte elastase, cathepsin G, and azurocidin. Three main differences are described between PR3 and the other serine proteases. This makes PR3 a very intriguing protein with a large array of physiological functions, some of which may play a role in ANCA-associated vasculitidis and myeloid leukemia.

Animals↗
PubMed2000

Recombinant proteinase 3 produced in different expression systems: recognition by anti-PR3 antibodies.

Anti-neutrophil cytoplasm autoantibodies (ANCA) directed against proteinase 3 (PR3) are highly sensitive and specific markers for Wegener's granulomatosis (WG). Consequently, antigen-specific assays for detection of PR3-ANCA are helpful for the diagnosis and follow-up of patients with WG. Purification of PR3 is laborious and requires large amounts of granulocytes. Therefore, several attempts have been made to produce recombinant PR3 that is recognized by PR3-ANCA. The purpose of this study was to compare the recognition of different recombinant forms of PR3 (rPR3) by anti-PR3 antibodies. Recombinant PR3 produced in E. coli (rcPR3), P. pastoris (rpPR3), insect cells using the baculovirus system (rbPR3), the human mast cell line, HMC-1 (HMC-1/PR3-S176A), or the human epithelial cell line, 293 (Delta-rPR3-S176A) as well as purified neutrophil PR3 (nPR3) were used. Recognition of these rPR3s by anti-PR3 antibodies was determined by direct and capture ELISA with 19 PR3-ANCA sera, 13 anti-PR3 mAbs and a rabbit serum raised against human PR3. In the capture ELISA rabbit anti-PR3 strongly bound nPR3 and all rPR3 products. By capture ELISA rcPR3 and rpPR3 were recognized by 11 (57%) and 13 (68%) of the 19 PR3-ANCA sera, respectively, whereas rbPR3, HMC-1/PR3-S176A, Delta-rPR3-S176A and nPR3 were recognized by all PR3-ANCA sera. By direct ELISA rabbit anti-PR3 strongly bound nPR3 and all tested rPR3 products. Using the direct ELISA none of the PR3-ANCA sera recognized rcPR3, whereas rpPR3 and rbPR3 were recognized by two (11%) and 17 (89%) of the 19 PR3-ANCA sera, respectively. All 13 anti-PR3 mAbs recognized nPR3 in the direct as well as in the capture ELISA. The rcPR3 was recognized by two mAbs in the capture ELISA but by none of the mAbs in the direct ELISA. The rpPR3 was recognized by seven mAbs in the capture ELISA and only by two mAbs in the direct ELISA. All but one of the anti-PR3 mAbs recognized rbPR3, whereas HMC-1/PR3-S176A and Delta-rPR3-S176A were recognized by all anti-PR3 mAbs. In conclusion, rPR3 expressed in insect cells, HMC-1 and 293 cells is recognized by anti-PR3 antibodies, whereas conformational epitopes recognized by anti-PR3 mAbs and PR3-ANCA are not well preserved on rPR3 expressed in E. coli or P. pastoris.

Adult↗
PubMed2000

Vasculitis: clinical approach, pathophysiology and treatment.

Systemic vasculitides constitute a heterogeneous group of diseases characterized by inflammation of blood vessels. Classification of the disease is mandatory for the assessment of prognosis and the institution of treatment. Secondary forms of vasculitis should be distinguished from primary vasculitides, as infections or other conditions underlying the secondary forms require a different approach. The presence of anti-neutrophil cytoplasmic antibodies (ANCA) directed against either proteinase 3 or myeloperoxidase strongly suggest one of the pauci-immune small vessel vasculitides. Their role in the pathogenesis of such vasculitides has been suggested by clinical and experimental data but has not been proven. Treatment of severe systemic vasculitides consists of cyclophosphamide in combination with corticosteroids but this regimen has many adverse effects. Less toxic regimens as well as new treatment modalities based on insight into the pathophysiology of systemic vasculitides have been developed and are currently being tested in multicentre European studies.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Prediction of relapses in Wegener's granulomatosis by measurement of antineutrophil cytoplasmic antibody levels: a prospective study.

OBJECTIVE: Prediction of relapses in Wegener's granulomatosis (WG) by measuring levels of antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) or myeloperoxidase (MPO) remains a controversial issue. To assess the value of serial quantification of ANCA by indirect immunofluorescence (IIF) and antigen-specific enzyme-linked immunosorbent assay (ELISA) for monitoring disease activity in patients with WG, a prospective observational study was conducted in patients with WG attending an outpatient clinic in the Netherlands. METHODS: One hundred patients with WG (85 with PR3-ANCA, 15 with MPO-ANCA) were studied prospectively from 1996 to 1998. Serum samples were obtained and analyzed every 2 months for ANCA levels. Disease activity was prospectively assessed without knowledge of the ANCA levels. RESULTS: Relapses occurred in 37 of 100 patients (37%). Thirty-four (92%) of the 37 patients showed a rise in the level of ANCA preceding their relapse, as detected by ELISA or IIF. The predictive value of an increase in ANCA titers for relapse was 57% (17 of 30) for cytoplasmic/classic ANCA (cANCA; by IIF), 71% (27 of 38) for PR3-ANCA (by ELISA), and 100% (3 of 3) for MPO-ANCA (by ELISA). The predictive value of a rise in ANCA as measured by ELISA or IIF did not substantially improve following concomitant measurement of the IgG3 subclass of PR3-ANCA. Forty-three percent of patients who showed a rise in cANCA (by IIF) and 29% with a rise in PR3-ANCA (by ELISA) did not subsequently experience a relapse. CONCLUSION: Serial measurement of ANCA levels is valuable for the early prediction of relapses in patients with WG.

Adult↗
PubMed2000

Fcgamma receptor polymorphisms in systemic lupus erythematosus: association with disease and in vivo clearance of immune complexes.

OBJECTIVE: Fc receptors for IgG (FcgammaR) play a prominent role in the clearance of immune complexes in systemic lupus erythematosus (SLE). Polymorphisms of FcgammaR have been proposed as genetic factors that influence susceptibility to SLE. We analyzed 3 functional FcgammaR polymorphisms in a strictly Caucasian population of SLE patients, and determined the influence of these polymorphisms on the clearance of immune complexes in vivo. METHODS: Genomic DNA was isolated from 230 Caucasian patients with SLE and 154 controls. Amplification of FcgammaR-genomic regions in allotype-specific polymerase chain reactions was used to distinguish the genotypes. In addition, we analyzed the FcgammaR genotypes of 13 patients with SLE who participated in a study determining the half-life of IgG-coated erythrocytes in the blood. RESULTS: We found a strong trend toward skewing of FcgammaRIIa, with an enrichment of the homozygous FcgammaRIIa-R/R131 genotype in patients compared with controls. We did not find a correlation between this genotype and the development of lupus nephritis. However, we established that the half-life of IgG-coated erythrocytes in the blood was prolonged in patients expressing the FcgammaRIIa-R/R131 genotype. The homozygous FcgammaRIIIa-F/F158 genotype was found more frequently in patients with arthritis and/or serositis. CONCLUSION: In Caucasian populations, the R/H polymorphism of FcgammaRIIa is a minor determinant in susceptibility to SLE, whereas the V/F polymorphism of FcgammaRIIIa is associated with a set of disease manifestations. Notably, the R/H polymorphism of FcgammaRIIa affects the clearance of immune complexes in vivo, which may influence the course of a disease such as SLE.

Adolescent↗
PubMed2000

Leukocyte activation in sepsis; correlations with disease state and mortality.

OBJECTIVE: The immune response in sepsis shows a bimodal pattern consisting of an early, frequently exaggerated inflammatory response followed by a state of hyporesponsiveness often referred to as the compensatory anti-inflammatory response syndrome (CARS). Insight into the disease state may be helpful in deciding whether to choose immune stimulatory or anti-inflammatory therapy in these patients and may determine clinical outcome. We hypothesized that poor outcome in patients with sepsis is related to the severity of CARS, as reflected in the degree of leukocyte activation. DESIGN: Prospective study. SETTING: Intensive and respiratory care unit at a university hospital. PATIENTS: Twenty consecutive patients with sepsis and 20 healthy age-matched volunteers. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Analysis of surface expression of HLA-DR, CD11b, ICAM-1, CD66b, CD63 and CD64 on neutrophils and monocytes by flow cytometry and determination of plasma concentrations of lactoferrin, interleukin 6 and neopterin by ELISA at the time of diagnosis. Patient data were related to those of controls; moreover patient data between survivors and non-survivors were compared. Increased expression of all markers, except HLA-DR, was observed on both neutrophils and monocytes from patients compared to healthy controls. HLA-DR expression on monocytes was significantly decreased in patients with sepsis (p < 0.01). Expression of CD11b and HLE on neutrophils, and ICAM-1 on monocytes, were lower in patients who died compared to those who survived (p < 0.05). CONCLUSION: In sepsis, both neutrophils and monocytes are activated compared to healthy controls. Poor prognosis is associated with a lower expression of activation markers on monocytes and neutrophils, suggesting that poor outcome in these patients may be due to the compensatory anti-inflammatory response.

Adult↗
PubMed2000

Lack of endothelial nitric oxide synthase aggravates murine accelerated anti-glomerular basement membrane glomerulonephritis.

Nitric oxide (NO) radicals generated by endothelial nitric oxide synthase (eNOS) are involved in the regulation of vascular tone. In addition, NO radicals derived from eNOS inhibit platelet aggregation and leukocyte adhesion to the endothelium and, thus, may have anti-inflammatory effects. To study the role of eNOS in renal inflammation, the development of accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was examined in mice lacking a functional gene for eNOS and compared with wild-type (WT) C57BL/B6j mice. WT C57BL/6j mice (n = 12) and eNOS knockout (-/-) mice (n = 12) were immunized intraperitoneally with sheep IgG (0.2 mg in complete Freund's adjuvant). At day 6.5 after immunization, mice received a single i.v. injection of sheep anti-mouse GBM (1 mg in 200 microl PBS). Mice were sacrificed at day 1 and 10 after induction of the disease. All WT mice survived until day 10, whereas 1 eNOS-/- mouse died and 2 more became moribund, requiring sacrifice. At day 10, eNOS-/- mice had higher levels of blood urea nitrogen than WT mice (P < 0.02), although proteinuria was comparable. Immunofluorescence microscopy documented similar IgG deposition in both WT and eNOS-/- mice, but eNOS-/- mice had more extensive glomerular staining for fibrin at day 10 (P < 0.007). At day 10, light microscopy demonstrated that eNOS-/- mice had more severe glomerular thrombosis (P < 0.003) and influx of neutrophils (P < 0. 006), but similar degrees of overall glomerular endocapillary hypercellularity and crescent formation. In conclusion, accelerated anti-GBM glomerulonephritis is severely aggravated in eNOS-/- mice, especially with respect to glomerular capillary thrombosis and neutrophil infiltration. These results indicate that NO radicals generated by eNOS play a protective role during renal inflammation.

Animals↗
PubMed2000

Clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune liver diseases.

BACKGROUND/AIMS: The clinical relevance of anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune liver disease is unclear. Defining the antigenic specificities of ANCA in these diseases may improve their clinical significance. METHODS: We studied the target antigens of ANCA in 88 patients with autoimmune hepatitis, 53 patients with primary biliary cirrhosis, and 55 patients with primary sclerosing cholangitis by indirect immunofluorescence, antigen-specific enzyme-linked immunosorbent assays, and immunodetection on Western blot, using an extract of whole neutrophils as a substrate. We related the data to clinical symptoms of autoimmune liver disease. RESULTS: By indirect immunofluorescence, ANCA were present in 74% of patients with autoimmune hepatitis, 26% of patients with primary biliary cirrhosis, and 60% of patients with primary sclerosing cholangitis. Major antigens were catalase, alpha-enolase, and lactoferrin. The presence of ANCA as detected by indirect immunofluorescence was associated with the occurrence of relapses in autoimmune hepatitis, with decreased liver synthesis function in primary biliary cirrhosis and in primary sclerosing cholangitis, and with increased cholestasis in primary sclerosing cholangitis. ANCA of defined specificities had only limited clinical relevance. CONCLUSIONS: ANCA as detected by indirect immunofluorescence seem associated with a more severe course of autoimmune liver disease. The target antigens for ANCA in these diseases include catalase, alpha-enolase, and lactoferrin. Assessment of the antigenic specificities of ANCA in autoimmune liver disease does not significantly contribute to their clinical significance.

Adolescent↗
PubMed2000

Staphylococcal acid phosphatase binds to endothelial cells via charge interaction; a pathogenic role in Wegener's granulomatosis?

The majority of patients with Wegener's granulomatosis (WG) are chronic nasal carriers of Staphylococcus aureus. Chronic nasal carriage of S. aureus is associated with an increased risk of developing a relapse of the disease. The mechanism by which this occurs is still unknown. We hypothesized that a cationic protein of S. aureus, staphylococcal acid phosphatase (SAcP), acts as a planted antigen and initiates glomerulonephritis and vasculitis in patients with WG. In order to test the hypothesis that SAcP can act as a planted antigen in WG, we studied the ability of SAcP to bind to human umbilical vein endothelial cells (HUVEC) and human glomerular endothelial cells. We also studied whether this binding can be prevented by preincubation with an anionic protein, and whether binding of SAcP activates endothelial cells. We also evaluated whether antibodies in sera of patients with WG are able to bind to endothelial cell-bound SAcP. The results show that SAcP can act as a planted antigen by binding to both types of endothelial cells in a concentration-dependent manner. Binding of concentrations as low as 4 microg/ml can be detected on HUVEC within 5 min of incubation. Binding of SAcP to endothelial cells was charge-dependent but did not activate endothelial cells. Finally, endothelial cell-bound SAcP was recognized by sera of patients with WG. The data suggest a possible pathogenic role for SAcP by acting as a planted antigen thereby initiating glomerulonephritis and vasculitis in patients with WG.

Acid Phosphatase↗
PubMed2000

In vitro T lymphocyte responses to proteinase 3 (PR3) and linear peptides of PR3 in patients with Wegener's granulomatosis (WG).

T cell-mediated immunity is thought to play an important role in the pathogenesis of WG. In previous studies a minority of WG patients as well as some healthy controls showed in vitro proliferation of their peripheral blood mononuclear cells (PBMC) to PR3, the main autoantigen in WG. The relevant peptides responsible for this in vitro proliferation have not been identified. In order to define immunogenic peptides, PBMC of 13 WG patients in remission and 10 healthy controls were tested for proliferation to linear peptides of PR3 and to whole PR3. Fifty overlapping peptides spanning the whole PR3 sequence were synthesized. Peptides were tested in pools of five peptides and as single peptide. PBMC of two WG patients and one healthy control proliferated to whole PR3 and to peptide pools. In addition, 10 WG patients and eight healthy controls that did not proliferate to whole PR3 did proliferate to pools of PR3 peptides. Although more WG patients tended to react to particular peptide pools, no significant difference was seen between lymphocyte proliferation to PR3 peptides of WG patients and that of healthy controls. The pools of peptides recognized were mainly located at the N- and C-terminus of PR3. No correlation was observed between HLA type and proliferation on particular peptide pools. No proliferation of PBMC was observed to single peptides. In conclusion, T cells of WG patients proliferate in vitro more frequently to PR3 peptides than to the whole PR3 protein. Peptides derived from the signal sequence, the propeptide or peptides located at the C-terminus of PR3 induce highest levels of proliferation. No specific PR3 sequence could be identified that was preferentially recognized by PBMC of WG patients compared with controls.

Adult↗
PubMed2000

Antiproteinase 3- and antimyeloperoxidase-associated vasculitis.

Antiproteinase 3- and antimyeloperoxidase-associated vasculitis. Wegener's granulomatosis, microscopic polyangiitis, and idiopathic pauci-immune necrotizing crescentic glomerulonephritis (NCGN) are strongly associated with antineutrophil cytoplasmic autoantibodies (ANCAs) directed against either proteinase 3 (anti-PR3) or myeloperoxidase (anti-MPO). This has led some investigators to prefer combining these diseases under the common heading of ANCA-associated vasculitides. However, it is increasingly recognized that there are characteristic differences between patients with anti-PR3 and those with anti-MPO-associated vasculitis. This review focuses on the clinical, histopathologic, and possibly pathophysiologic differences between anti-PR3- and anti-MPO-associated vasculitis. Although there is considerable overlap, the anti-PR3- and anti-MPO-associated vasculitides are each characterized by particular clinical and histopathological findings. Extrarenal organ manifestations and respiratory tract granulomas occur more frequently in patients with anti-PR3 than in those with anti-MPO. Anti-PR3-positive patients with NCGN generally have a more dramatic deterioration of their renal function compared with anti-MPO-positive patients. The term "ANCA-associated vasculitis" is considered as a useful concept in the presence of systemic vasculitis. Likewise, in the presence of vasculitis, the terms "anti-PR3-associated vasculitis" and "anti-MPO-associated vasculitis" are useful concepts.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

Is Wegener's granulomatosis an autoimmune disease?

Wegener's granulomatosis is a multisystem disease characterized by granulomata of the respiratory tract and systemic necrotising vasculitis. There is a strong and specific association with autoantibodies directed against proteinase 3, a constituent of neutrophril azurophilic granules. Antibody titers correlate with clinical disease activity and predict relapses. The disease responds favorably to immunosuppressive therapy. The pathogenicity of antineutrophil cytoplasmic antibodies (ANCA), however, remains unproven. In vitro, the expression of proteinase-3 and other ANCA antigens on the surface of neutrophils and monocytes can be induced by priming with proinflammatory cytokines. Antineutrophil cytoplasmic antibodies are then able to activate these leukocytes, stimulating degranulation, the production of reactive oxygen species, and the secretion of further cytokines. Neutrophils activated by ANCA, and possibly ANCA alone, directly damage endothelial cells in vitro. An animal model of proteinase 3-ANCA-induced vasculitis has not been found. Antineutrophil cytoplasmic antibodies directed against another antigen, myeloperoxidase, are not sufficient to cause vasculitis but they promote damage in certain animal models. Thus, a considerable amount of evidence supports the notion that Wegener's granulomatosis is an autoimmune disease.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

New treatments of ANCA-associated vasculitis.

The ANCA-associated systemic vasculides are, in many cases, life-threatening conditions. Combined treatment with corticosteroids and cyclophosphamide has improved their prognosis considerably. Five year survival does, however, still not exceed 75%, due to the occurrence of treatment resistant cases and the severe adverse effects of this treatment regimen. In this review new treatment modalities are discussed. In cases resistant to conventional therapy high dose intravenous immunoglobulin and T-cell directed biologicals, that is anti-thymocyte globulin (ATG) and humanised monoclonal antibodies to CD4 and CDw52, may be effective. Also, TNF-directed treatment is being used. Less severe cases may benefit from methotrexate treatment instead of cyclophosphamide. For maintenance of remission azathioprine has been proven to be as effective as cyclophosphamide so preventing the toxicity of long-term cyclophosphamide treatment. Relapses may also be prevented by treatment based on changes in ANCA-titers or by elimination of Staphylococcus aureus carriage which is associated with relapsing disease in Wegener's Granulomatosis. Several of those new treatment modalities are now being tested in controlled studies by the European Vasculitis Study Group (EUVAS).

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

Fcgamma receptor polymorphisms in Wegener's granulomatosis: risk factors for disease relapse.

OBJECTIVE: Several studies have recently identified polymorphisms of receptors for the Fc fragment of IgG (FcgammaR) as genetic factors influencing susceptibility to multiple autoimmune and infectious diseases. This genetic predisposition could also influence the expression of Wegener's granulomatosis (WG), a systemic autoimmune disease with chronic nasal carriage of Staphylococcus aureus as an important risk factor for disease relapses. Therefore, we analyzed 3 functional FcgammaR polymorphisms from 91 patients with WG and 154 controls for a possible relationship with disease expression and occurrence of relapses. METHODS: FcgammaR phenotypes were determined using amplification of FcgammaR-genomic regions in allotype-specific polymerase chain reactions. Of particular interest in the analysis were 2 allotypic forms of FcgammaRIIa (R131 or H131) and 2 allotypic forms of FcgammaRIIIa (V158 or F158), all of which are functionally different. RESULTS: Analysis of FcgammaR phenotypes demonstrated that patients with WG were more prone to disease relapse in the first 5 years after diagnosis if they were homozygous for both the R131 form of FcgammaRIIa and the F158 form of FcgammaRIIIa (relative risk 3.3, 95% confidence interval 1.6-6.8). These polymorphisms are both associated with decreased FcR-mediated clearance, which may be relevant to the chronic nasal carriage of S aureus. CONCLUSION: Both the R/H131 polymorphism of FcgammaRIIa and the V/F158 polymorphism of FcgammaRIIIa represent heritable risk factors for the development of disease relapses in WG.

Adult↗
PubMed1999

Differential B- and T-cell activation in Wegener's granulomatosis.

BACKGROUND: Autoimmune mechanisms are postulated to play a role in the development and progression of Wegener's granulomatosis (WG), a form of systemic, idiopathic necrotizing vasculitis. OBJECTIVE: We investigated the relation between lymphocyte activation and disease activity in patients with WG. METHODS: B- and T-lymphocyte activation was studied by cytometric assessment of the expression of the activation markers CD38 on B cells and CD25 and HLA-DR on CD4(+) and CD8(+) T-cell subsets, respectively. Activation at the cellular level was related to serum levels of antineutrophil cytoplasmic antibodies and soluble IL-2 receptor, which can be regarded as soluble activation markers of B and T cells. RESULTS: Percentages of CD38(bright) activated B cells were higher in patients with active WG than in patients experiencing disease remission (P <.05) or in healthy control subjects (P <.05). Percentages of activated CD4(+) and CD8(+) T cells were higher in patients with active WG (CD4 subset, P <.0001; CD8 subset, P <.005) than in healthy individuals. An increased percentage of activated T cells of both subsets was also seen in patients whose condition was in remission, as compared with healthy control subjects (CD4 subset, P <.0005; CD8 subset, P <. 001). Lymphocyte activation at the cellular level did not correlate with plasma levels of antineutrophil cytoplasmic antibodies or soluble IL-2 receptor. CONCLUSION: In WG, B-cell activation is related to active disease, whereas T-cell activation persists during remission of the disease, which points to an intrinsic disordered immune system in this disease.

Adult↗