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M Trendelenburg

Publications and source records attributed to M Trendelenburg.

At least 19 recordsLinked to original sources
PubMed2006

Anti-C1q antibodies in hepatitis C virus infection.

Autoantibodies against C1q have been described in many immune-complex diseases including hypocomplementaemic urticarial vasculitis and systemic lupus erythematosus (SLE). No study has focused on the role of anti-C1q antibodies in hepatitis C virus (HCV) infection. The aim of this study was (i) to evaluate the prevalence of anti-C1q antibodies in HCV infection; and (ii) to analyse the association of anti-C1q antibodies with clinical and biological features of HCV-mixed cryoglobulinaemia (MC) vasculitis. We searched for anti-C1q antibodies using an enzyme-linked immunosorbent assay (ELISA) test in 111 HCV patients (75 had cryoglobulin and 23 systemic vasculitis), 60 SLE patients and 109 blood donors. Anti-C1q antibodies were detected in 26% of HCV patients compared to 10% of healthy donors (P < 0.01), and 38% in patients with SLE. Although there was a higher prevalence of anti-C1q antibodies among HCV patients with type III cryoglobulin (50%, P < 0.01), the overall prevalence of anti-C1q antibodies was similar in HCV patients being cryoglobulin-positive or cryoglobulin-negative (26%versus 25%, P = 0.98). A significant association was found between anti-C1q antibodies and low C4 fraction of complement (P < 0.05). No association was found between anti-C1q antibodies and HCV genotype, severity of liver disease or with specific clinical signs of HCV-MC vasculitis. This study shows an increased prevalence of anti-C1q antibodies in HCV-infected patients. Anti-C1q antibodies were associated with low C4 levels. No association was found between anti-C1q antibodies and HCV-MC vasculitis, nor between anti-C1q antibodies and cryoglobulinaemia.

Aged↗
PubMed2005

[Pathogenesis of systemic lupus erythematosus (SLE)--the central role of complement].

The traditional view of the pathogenesis of SLE is that immune complexes containing autoantigens and autoantibodies activate complement, and that this causes inflammatory injury to tissues. Although this model is biologically plausible, it cannot account for all of the clinical observations that link the complement system and SLE. In particular, the observation that complement deficiency causes lupus is hard to reconcile with the concept that complement activation products are the major cause of inflammatory injury in the disease. More recent data suggests that the role of complement in SLE is rather protective. Bindung of complement might prevent an autoimmune response by supporting the clearance of immuncomplexes and apoptotic cell debrid.

Animals↗
PubMed2003

Autoantibodies against complement receptor 1 (CD35) in SLE, liver cirrhosis and HIV-infected patients.

The acquired loss of CR1 (CD35) on erythrocytes in specific autoimmune diseases and chronic infections may be due to autoAb against CR1. An ELISA using rCR1 was established to measure antiCR1 IgG autoAb. Plasma containing alloAb to polymorphism on CR1 (Knops blood group Ab) reacted strongly against rCR1 and were used as positive controls. AntiCR1 Ab was found in 3/90 (3.5%) plasma samples from healthy blood donors. The binding of these Ab was not inhibited by high salt concentrations. AntiCR1 Ab were present in the IgG fractions of plasma, and they bound to rCR1 on Western Blot. Affinity chromatography on rCR1-sepharose depleted the plasma of antiCR1, and the acid-eluted fractions contained the antiCR1 Ab. An increased frequency of antiCR1 autoAb was found in patients with SLE (36/78; 46%), liver cirrhosis (15/41; 36%), HIV infection (23/76; 30%) (all P < 0.0001), and in patients with anticardiolipin Ab (4/21; 19%, P < 0.01) multiple sclerosis (7/50; 14%, P < 0.02), and myeloma (autoAb (8/56; 14%, P < 0.02), but not in those with acute poststreptococcal glomerulonephritis (1:32; 3%). Because C1q binds to CR1, antiC1q Ab were analysed in the same patients. There was no correlation between levels of antiC1q and antiCR1 autoAb. In HIV patients, levels of antiCR1 did not correlate with low CR1 levels expressed on erythrocytes or soluble CR1 in plasma. The binding of antiCR1 autoAb to rCR1 fixed on ELISA plates was not inhibited by soluble rCR1 or by human erythrocyte CR1, in contrast to alloAb and one SLE serum, which induced partial blockade. Thus, antiCR1 autoAb recognize mostly CR1 epitope(s) not present on the native molecule, suggesting that they are not directly involved in the loss of CR1. Rather antiCR1 autoAb might indicate a specific immune response to denatured CR1.

Autoantibodies↗
PubMed2003

Cryoglobulin/albumin complexes in a patient with severe autoimmune syndrome.

We describe the case of a 30-year-old man with a severe autoimmune disease characterized by cryoglobulinaemia, pulmonary hypertension, Raynaud's phenomenon, lymphadenopathy, and glomerulonephritis. Despite initial remission following autologous stem cell transplantation, his disease relapsed and he died from pulmonary hypertension. At presentation the patient had hypergammaglobulinaemia and a number of autoantibodies, including rheumatoid factor (1:10240). The most striking feature was the extremely high level of cryoglobulins. The cryoprecipitate consisted of polyclonal IgM, IgG and albumin. Interestingly, the albumin in the cryoprecipitate was exclusively present in SS-bonded oligomeric forms, and contained an abnormal acidic component as judged by 2D gel electrophoresis. Oxidized albumin was also present in serum, and represented a small but significant fraction. None of the many known albumin variants have so far been associated with a particular disease; thus our results may represent the first description of an altered albumin associated with severe disease.

Adult↗
PubMed2001

Disseminated scabies evolving in a patient undergoing induction chemotherapy for acute myeloblastic leukaemia.

We report on a 34-year-old refugee from the Balkans presenting with a generalized papular rash during induction chemotherapy for acute myeloblastic leukaemia (AML M4eo). This rash appeared on day 5 of the chemotherapy and was diagnosed as disseminated scabies. It was successfully treated with a combination of oral ivermectin and topical lindane. Scabies disappeared completely despite ongoing neutropenia and other severe infectious complications. Disseminated scabies should be included in the differential diagnosis of rash in severely immunosuppressed patients coming from poor housing conditions.

Adult↗
PubMed2001

Anti-C1q antibodies may help in diagnosing a renal flare in lupus nephritis.

It is still uncertain which, if any, immunologic parameters may help diagnose a renal flare of lupus nephritis. Anti-C1q antibody (Ab) titers have been elevated in patients with lupus with renal involvement, but little information is available on whether the titers are different in quiescent and active phases of lupus nephritis. In this study, we compared anti-C1q Ab titers with other serological test results in 48 patients with biopsy-proven lupus nephritis to assess which parameter could offer the best reliability for differentiating between quiescent and active phases of lupus nephritis. Serum C3 and C4 levels, as well as anti-double-stranded DNA, antiendothelial cell, anti-C1q, and antiphospholipid Ab titers, were evaluated in patients with quiescent renal disease (38 samples) and those with clinical evidence of renal activity (23 samples). Only anti-C1q Ab titers correlated with active renal disease in both univariate (P < 0.0001) and multivariate analysis (P < 0.0001), with a sensitivity of 87% and a specificity of 92%. In six patients, immunologic parameters were measured serially. In all patients, the high anti-C1q Ab titers returned to normal values after treatment-induced remission. The other serological parameters did not show a significant association with renal disease activity. In patients with biopsy-proven lupus nephritis, anti-C1q Ab titers appear to be strongly related to renal disease activity. Their measurement may be useful for confirming the diagnosis of renal flares of lupus nephritis.

Adult↗
PubMed2000

[New physiopathological findings in paraproteinemias].

Apart from their antigen-recognising function, immunoglobulins have other physicochemical properties. The best described is cryoprecipitation of monoclonal and/or polyclonal immunoglobulins. The cryoprecipitation phenomenon is unique for each cryoglobulin, and depends on the intrinsic properties of the monoclonal immunoglobulin, the protein environment, temperature and the surrounding ionic concentrations. The complement activating properties of monoclonal immunoglobulins are also unique. We have described a series of monoclonal immunoglobulins which are able to activate the classical pathway of complement without the formation of antigen/antibody complexes. Analysis of the properties of these monoclonal immunoglobulins suggests new therapeutic strategies in oncology. Monoclonal chimeric antibodies, combining antibody specific against tumour antigens and strong complement activation, may be more damaging to tumor cells than currently used antibodies.

Complement Pathway, Classical↗
PubMed2000

[Apoptosis and C1q: possible explanations for the pathogenesis of systemic lupus erythematosus].

Dysregulation of apoptosis may play a major role in the pathogenesis of systemic lupus erythematosus (SLE). A defective clearance of apoptotic cells or inappropriately high rates of apoptosis may lead to a pathologic accumulation of abnormal cell material with a secondary autoimmune response. Experimental findings in apoptotic keratinocytes and C1q knock-out mice suggest an important role of C1q in the clearance of apoptotic cell material. In addition, there are several links between C1q and SLE: Most the patients with C1q deficiency develop a SLE-like syndrome. SLE itself often causes secondary C1q deficiency and autoantibodies to C1q are detected in almost all patients with active lupus nephritis. These observations suggest a central role of C1q in apoptosis and in the pathogenesis of SLE.

Animals↗
PubMed1999

Monomeric complement-activating IgG paraproteins.

Three patients presented a unique syndrome of recurrent panniculitis with an IgGkappa paraprotein and depletion of the early components of the classical pathway of complement. The IgGkappa paraproteins were monomers with a normal structure, and with no evidence for aggregation, as assessed by electron microscopy and ultracentrifugation. Both heavy and light chains were of normal molecular size (SDS-PAGE), and the paraproteins were not heavily glycosylated. However, the paraproteins from all three patients had unusual features that included abnormal behavior on gel filtration chromatography and a heavy chain of high pI. When analyzed by fast protein liquid chromatography (Superdex 200), elution of the paraproteins was retarded, particularly when the ionic strength was increased. This retardation was partially reversed in 20% alcohol, and fully reversed in 6 M guanidine-HCl. Neither anti-C1 inhibitor nor anti-C1q autoantibodies were found in any of the patients' sera. However, the paraproteins bound to the globular heads of C1q at normal ionic strength. They activated C4 in normal human serum, but not in C1q-deficient serum. Activation led to the formation of C1s-C1 inhibitor complexes. Taken together, the data suggest that the unusual paraproteins have the capacity to bind C1q, which then leads to activation of C1. The ability of these paraproteins to activate C1, in spite of their being soluble monomers, is likely to be related to their unique physicochemical features.

Chromatography, Gel↗
PubMed1999

Concomitant blockade of P2X-receptors and ecto-nucleotidases by P2-receptor antagonists: functional consequences in rat vas deferens.

In order to assess the consequences of a concomitant blockade of P2X-receptors and ecto-nucleotidases, effects of 13 P2-receptor antagonists were investigated on contractions of the rat vas deferens elicited by alpha,beta-methylene ATP (alpha,beta-MeATP) and ATP and on the removal of ATP from the incubation medium by vas deferens tissue. Increasing concentrations of all antagonists reduced and finally abolished contractions elicited by alpha,beta-MeATP (3 microM), with IC50-values ranging from 1.1 to 100 microM. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonate (PPADS), 6-azophenyl-4-amino-5-hydroxy-naphthalene-1,3-disulphonate (NH02), 4,4'-diisothiocyanatostilbene-2,2'-disulphonate (DIDS) and uniblue A also progressively reduced and finally abolished contractions elicited by ATP (1 mM). 8,8'-[Carbonylbis(imino-3, 1-phenylenecarbonyl-imino)]-bis-(1,3,5-naphthalenetrisulphonate ) (NF023), suramin, pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS), trypan blue and reactive blue 19, in contrast, caused only partial blockade, by 34-43% maximally; reactive blue 2 and reactive red 2 had no effect; and 6,6'-(1,1'-biphenyl-4,4'-diylbisazo)-bis-4-amino-5-hydroxy-naphtha lene-1,3-disulphonate (NH01) and Evans blue even enhanced the response to ATP. For antagonists causing full or partial inhibition, the IC50-values against ATP were close to those against alpha,beta-MeATP. All antagonists attenuated the removal of ATP, with IC25%-values ranging from 0.8 microM to >320 microM. The results confirm the frequent combination, in one antagonist molecule, of P2-receptor blockade and blockade of ecto-nucleotidases. This dual action underlies the effect of such compounds on contractions of the vas deferens elicited by ATP which, for certain substances (e.g., suramin, reactive blue 2), can be explained by a simple model in which the antagonist simultaneously blocks the degradation of ATP and a single contraction-mediating receptor (P2X1). Several observations, however, do not conform with this model, and the existence of multiple contraction-mediating receptors for ATP or multiple, pharmacologically distinct ecto-nucleotidases has to be considered.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

Hepatitis virus-related and ethanol-induced chronic liver disease with or without cryoglobulins--is there a difference concerning clinical or laboratory manifestation?

Mixed cryoglobulinemia is frequent in southern Europe and attributed to hepatitis C infection. We analyzed prevalence and clinical symptoms of mixed cryoglobulinemia in our region among patients with chronic hepatitis C (n = 29) and B (n = 7) in comparison to alcoholic liver cirrhosis without evidence of hepatitis virus infection (n = 10). Cryoglobulinemia was found in 13/29 patients with hepatitis C (11 type III, one type I1-III and one type II), 2/7 with hepatitis B (one type II, one type III) and 4/10 with alcoholic liver cirrhosis (one type II, three type III). Patients with moderate active hepatitis had more type II than type III cryoglobulins. Concerning clinical symptoms, only sicca syndrome was more frequent in patients with hepatitis C. Rheumatoid factor (RF) and immune globulin M (IgM) levels were higher in hepatitis C than in the other groups. Renal disease was rare in all but not different between the groups. Mixed cryoglobulinemia in hepatitis C (and B) is most frequently of type III. Patients with hepatitis C had the same prevalence of cryoglobulins as patients with alcoholic liver cirrhosis. Cryoglobulins had no influence on clinical syndromes or organ damage.

Adolescent↗
PubMed1999

Hypocomplementemic urticarial vasculitis or systemic lupus erythematosus?

The 2 patients presented here showed the typical signs of hypocomplementemic urticarial vasculitis syndrome (HUVS). During follow-up, there was an inverse correlation between anti-C1q autoantibody titer and C1q antigen concentration in serum in both patients over a period of 2 years. The first patient had nephritis characterized by immune deposits in glomeruli and around the tubules. The histological findings, C1q deposits, and presence of tubuloreticular inclusions in capillary endothelial cells suggested a disease process identical to systemic lupus erythematosus (SLE). The second patient, after a lag phase of 2 years, fulfilled a fourth American College of Rheumatology criteria for SLE when she developed anti-double-stranded DNA antibodies. HUVS and SLE overlap, and the criteria for identifying HUVS as an entity distinct from SLE are lacking.

Adult↗
PubMed1998

Correction of spurious blood cell counts in a patient with cryoglobulinemia reversed by the use of citrate-anticoagulated blood.

Cryoglobulins may interfere with automated cell counting when proteins precipitate or blood cells aggregate. This results in spurious platelet or leukocyte counts, false values for red blood cell parameters and abnormal scattergrams. Usually it can be reversed by warming blood specimens to 37 degrees C. We describe the case of a 63-year-old woman with autoimmune disease in whom the diagnosis of cryoglobulinemia was suspected due to typical changes in blood cell counts. Artifacts were resistant to warming of the sample to 37 degrees C in both EDTA- and heparin-anticoagulated blood specimens. In contrast, the use of citrate as anticoagulant allowed correct measurements. This case underlines the role of assessment of blood counts in the detection of cryoglobulinemia. Correct measurements of automated blood counts in cryoglobulinemia may depend on the use of alternative anticoagulants.

Anticoagulants↗