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1.
V L Esnault D R Jayne M T Keogan A A Brownlee A Testa D Lecarrer D L Brown C M Lockwood 《Journal of clinical & laboratory immunology》1990,32(4):153-159
Anti-neutrophil cytoplasm antibodies (ANCA) are specific markers for systemic vasculitis. In view of the autoreactivity to other autoantigens reported in patients with monoclonal immunoglobulins (MIg), the reactivity of 150 sera from 125 patients with MIg was tested for ANCA by radioimmunoassay (RIA) with inhibition stage and indirect immunofluorescence (IIF). Seven were positive for IgG ANCA, all with IgG MIg and 5 were positive for IgM ANCA, 4 with IgM MIg and 1 with IgG MIg. No IgA ANCA were found. The patterns seen on IIF were identical to those seen with sera from patients with systemic vasculitis and were cytoplasmic in 6 and peri-nuclear in 6. The restriction of the ANCA activity to the MIg was studied in six sera by light chain specific RIA, and anion exchange fractionation of the sera. The ANCA activity appeared to be polyclonal in at least three sera and could be found in the monoclonal fraction in only three patients. Associated autoimmune diseases were found in some of these ANCA positive patients including Sj?gren's syndrome, MacDuffie hypocomplementemic vasculitis and rheumatoid polyarthritis but the classical vasculitic features normally associated with ANCA were not observed. We conclude that ANCA is a further autoreactivity present in some sera with MIg and discuss the relation between monoclonal gammopathies and autoimmunity. 相似文献
2.
Seaton RA; Naraqi S; Wembri JP; Warrell DA 《QJM : monthly journal of the Association of Physicians》1996,89(6):423-428
In Papua New Guinea, <it>Cryptococcus neoformans</it> var.
<it>gattii</it> meningitis has a high fatality rate even in
immunocompetent patients. Our retrospective study attempted to identify
marker of poor prognosis. Of 88 immunocompetent patients, 30 (34.1%) died,
usually soon after admission, and mortality was higher in men
(<it>p</it> = 0.025) and older patients (<it>p</it>
= 0.039). Death was associated with altered consciousness
(<it>p</it><0.001), a history of convulsions prior to
treatment (<it>p</it> = 0.002) and a maximum systolic blood
pressure of >150 mmHg (<it>p</it> = 0.017). These data
suggest that death results from raised intracranial pressure and subsequent
tentorial herniation. However, CSF opening pressure measured on admission
was raised in 29/36 (81%) patients and did not predict outcome. In
survivors, relapse was uncommon and was not predicted by discharge serum
cryptococcal antigen titres, which were frequently raised on completion of
therapy in asymptomatic patients. Mortality may be reduced if efforts are
made to lower intracranial pressure in those patients who present with
markers of poor prognosis.
相似文献
3.
Early surgery in infective endocarditis 总被引:4,自引:0,他引:4
Olaison L; Hogevik H; Myken P; Oden A; Alestig K 《QJM : monthly journal of the Association of Physicians》1996,89(4):267-278
Optimal timing of surgical intervention in infective endocarditis is
important in reducing mortality. We prospectively studied 126 consecutive
episodes of infective endocarditis treated in one institution over 5 years,
with special emphasis on long-term results and on the effects on outcome of
surgical interventions. Twenty-six patients (21%) underwent acute surgery
on median treatment day 14. Mortality during treatment was 8% for patients
undergoing acute surgery vs. 11% for those not undergoing surgery, and the
adjusted 5-year survival rate of acute surgically treated patients was 91%,
compared with 69% for the medically treated patients. Using univariate
analysis, excess mortality during 5 years follow-up was associated with new
cardiac decompensation at entry (<it>p</it> < 0.01), age
(<it>p</it> < 0.01), no acute surgery
(<it>p</it> < 0.05) and mitral valve involvement
(<it>p</it> < 0.05). Multivariate analysis showed new
cardiac decompensation at entry to be an independent predictor of cardiac
death at 5 years follow-up (relative risk 2.39, CI 1.05-5.45), while no
surgery during active disease implied a relative risk of 3.45, though not
statistically significant. Patients undergoing surgery very early
(⩽ 10 days of treatment) did not have a poorer outcome. Acute valve
replacement, as compared with medical therapy only, might be important to
increase both short-term and long-term survival in infective endocarditis.
相似文献
4.
Genetic analysis of thermolabile methylenetetrahydrofolate reductase as a risk factor for myocardial infarction 总被引:3,自引:0,他引:3
Adams M; Smith PD; Martin D; Thompson JR; Lodwick D; Samani NJ 《QJM : monthly journal of the Association of Physicians》1996,89(6):437-444
Hyperhomocyst(e)inemia is associated with an increased risk of coronary
artery disease and myocardial infarction. Both genetic and environmental
factors influence the plasma level of homocysteine. One of the metabolic
pathways for homocysteine involves the enzyme methylenetetrahydrofolate
reductase (MTHFR), which regulates the conversion of homocysteine to
methionine. A thermolabile variant of MTHFR is associated with reduced
enzyme activity and increased plasma homocysteine levels. Recently, the
cause of this variant of MTHFR has been identified as a single base change
altering an alanine to a valine residue in the protein. Using a PCR-based
assay to distinguish the normal and thermolabile variants of MTHFR in this
study, we investigated whether the thermolabile variant is a genetic risk
factor for myocardial infarction. In a study of 532 subjects (310
myocardial infarction patients and 222 population-based controls), we found
no difference in either MTHFR genotype distribution (<it>p</it>
= 0.57) or allele frequencies (<it>p</it> = 0.68) between cases
and controls. The allele frequencies of the thermolabile variant were 0.34
and 0.35 in cases and controls, respectively. The age- and sex-stratified
odds ratio for risk of myocardial infarction associated with homozygosity
for the thermolabile variant was 0.85 (95% CI 0.50-1.50,
<it>p</it> = 0.57) and that with carriage of the thermolabile
allele was 1.06 (95% CI 0.73-1.52, <it>p</it> = 0.76). The odds
ratio remained non-significant when restricted to young subjects
(<60 years) or males, and were not influenced by several other risk
factors for myocardial infarction considered either singly or in
combination. Interestingly, in both cases and controls, there was a trend
toward a higher prevalence of hypertension in subjects carrying the normal
allele, although as this is a <it>post-hoc</it> finding it
needs to be interpreted with caution. The thermolabile variant of MTHFR is
not a major risk factor for myocardial infarction and is unlikely to
explain a significant proportion of the reported association of
hyperhomocyst(e)inemia with coronary artery disease.
相似文献
5.
Aleeza J. Roth Joshua D. Ooi Jacob J. Hess Mirjan M. van Timmeren Elisabeth A. Berg Caroline E. Poulton JulieAnne McGregor Madelyn Burkart Susan L. Hogan Yichun Hu Witold Winnik Patrick H. Nachman Coen A. Stegeman John Niles Peter Heeringa A. Richard Kitching Stephen Holdsworth J. Charles Jennette Gloria A. Preston Ronald J. Falk 《The Journal of clinical investigation》2013,123(4):1773-1783
Anti-neutrophil cytoplasmic antibody–associated (ANCA-associated) small vessel necrotizing vasculitis is caused by immune-mediated inflammation of the vessel wall and is diagnosed in some cases by the presence of myeloperoxidase-specific antibodies (MPO-ANCA). This multicenter study sought to determine whether differences in ANCA epitope specificity explain why, in some cases, conventional serologic assays do not correlate with disease activity, why naturally occurring anti-MPO autoantibodies can exist in disease-free individuals, and why ANCA are undetected in patients with ANCA-negative disease. Autoantibodies from human and murine samples were epitope mapped using a highly sensitive epitope excision/mass spectrometry approach. Data indicated that MPO autoantibodies from healthy individuals had epitope specificities different from those present in ANCA disease. Importantly, this methodology led to the discovery of MPO-ANCA in ANCA-negative disease that reacted against a sole linear sequence. Autoantibodies against this epitope had pathogenic properties, as demonstrated by their capacity to activate neutrophils in vitro and to induce nephritis in mice. The confounder for serological detection of these autoantibodies was the presence of a fragment of ceruloplasmin in serum, which was eliminated in purified IgG, allowing detection. These findings implicate immunodominant epitopes in the pathology of ANCA-associated vasculitis and suggest that autoantibody diversity may be common to other autoimmune diseases. 相似文献
6.
Clinical role of autoantibody against bactericidal/permeability-increasing protein in chronic airway infection 总被引:2,自引:0,他引:2
Osamu Kobayashi 《Journal of infection and chemotherapy》1998,4(2):83-93
Chronic airway infections often have persistent colonization of mucoid-derivative and/or biofilm-formed bacteria on the small
airway surface. Such long-term colonization by bacteria sometimes induces harmful immune reactions in the host. Bactericidal/permeability-increasing
protein (BPI) is one of the important agents in the phagocyte activity of neutrophils. An antineutrophil cytoplasmic autoantibody
against BPI (BPI-ANCA) was recently detected. The clinical role of BPI-ANCA in 66 patients with chronic airway infections
was investigated. Corresponding antigens in neutrophils against the antibody in their sera were observed by the indirect immunofluorescence
method. After confiriming the antigen to be BPI, the presence of BPI-ANCA in their serum samples was determined by the enzyme-linked
immunosorbent assay method. The titers were analyzed in relation to clinical symptoms, prognosis, and bacteriologic aspects,
including in vitro examinations. Thirty-five of 66 samples (53%) were positive for cytoplasmic ANCA, and 48 cases (73%) were
positive for serum BPI-ANCA. There were no positive cases among the sera samples of 7 healthy individuals. High titers of
BPI-ANCA and a high frequency of BPI-positive indications were seen in cases with persistent colonization of gram-negative
bacteria (P<0.05), and they also correlated with clinical symptoms and prognosis. In in vitro examinations, BPI-ANCA dose-dependently
suppressed BPI that was induced by the interaction of neutrophils and gram-negative bacteria. BPI-ANCA is characteristically
found in cronic infections, and it suppesses the BPI activity of neutrophils. An autoimmune manifestation such as this might
increase the intractability of chronic airway infections. 相似文献
7.
《Serodiagnosis and Immunotherapy in Infectious Disease》1997,8(3-4):207-212
Antigen derived from three major life-stages of human lymphatic filariid, Brugia malayi was fractionated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and reactivity of filarial antibodies, present in sera of human bancroftian patients belonging to different categories of the disease, to immunoreactive molecules was evaluated by Western blotting and immune recognition. Antigen molecules of >180, ~180, ~116, ~66, 58, 33 and <20 kDa were strongly identified in blots especially by symptomatic and endemic normal sera. Although mf positive serum reacted with the majority of these molecules, the intensity of bands was poor. These functional molecules along with ~43 kDa were later isolated from a preparative SDS-polyacrylamide gel by elution. The diagnostic utility of these purified molecules was then assessed by enzyme linked immunosorbent assay (ELISA) for detecting the IgG antibodies in patients' sera of various categories. Tropical pulmonary eosinophilic subjects revealed highest reactivity with <20 and ~116 kDa molecules while mf positive ones reacted feebly with the majority of the molecules except ~43 and ~66 kDa. Sera of endemic normals revealed high IgG levels but antibodies to ~ 66 kDa were highest. Symptomatic patients showed moderate reactivity. Non-endemic sera neither reacted in blots nor in ELISA. The study demonstrates the usefulness of ~43 kDa in detecting IgG antibodies of mf positive asymptomatic patients. High IgG levels to ~66 kDa followed by ~116 kDa and <20 kDa in sera of endemic normals warrants their immunoprophylactic evaluation. 相似文献
8.
Elio Tonutti Daniela Visentini Alessia Picierno Nicola Bizzaro Danilo Villalta Renato Tozzoli Graziano Kodermaz Antonio Carroccio Giuseppe Iacono Saverio Teresi Stella Maria La Chiusa Ignazio Brusca 《Journal of clinical laboratory analysis》2009,23(3):165-171
Background and Aim: We evaluated the diagnostic performance of an ELISA test for anti‐gliadin IgA and IgG antibodies, which uses synthetic deamidated gliadin peptides (anti‐gliadin antibodies, AGAs) as coating; the results were compared with a test that uses extracted gliadin (AGAe). Methods: The study was conducted on the sera of 144 patients suffering from celiac disease (CD), including 20 patients with IgA deficiency and 9 who were following a gluten‐free diet (GFD), and 129 controls. Results: In the 115 CD patients (without IgA deficiency), the sensitivity of AGAe IgA and IgG was 32.2 and 60.9%, whereas that of AGAs IgA and IgG was 59.1 and 72.2%. The specificity for AGAe IgA and IgG, and AGAs IgA and IgG was 93.8 and 89.9%, and 96.9% and 99.2%, respectively. Of the 20 patients with CD and IgA deficiency, 7 tested positive for AGAe IgG and 14 for AGAs IgG. The test using deamidated gliadin peptides performed better in terms of sensitivity and specificity than the AGA tests with extracted antigen. Conclusions: The very high specificity of the AGAs IgG test (99.2%) also suggests that patients who test positive with this assay require a thorough followup, even if the anti‐tissue transglutaminase antibodies (anti‐tTG) and anti‐endomysial autoantibodies (EMA) assays are negative. J. Clin. Lab. Anal. 23:165–171, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
9.
【目的】探讨IgA和IgG型抗中性粒细胞胞质抗体(ANCA)联合检测在韦格纳肉芽肿(WG)临床诊断中的应用价值。【方法】对28例临床诊断为wG及172例其他自身免疫性疾病患者血清,应用间接免疫荧光法检测ANCAIgA和IgG型抗体。【结果】wG病患者胞质型ANCA(cANCA)IgG型抗体和cANCAIgA型抗体阳性率最高,均显著高于其他自身免疫性疾病,且差异有显著性(P〈0.05)。联合检测ANCAIgG及IgA亚型抗体阳性率为89.3%(25/28),明显高于单独检测ANCAIgG或IgA亚型阳性率53.6%(15/28)和35.7%(10/28),且差异有显著性(P〈0.05)。【结论lIgA和IgG型抗中性粒细胞胞浆抗体联合检测有助于wG的早期准确诊断。 相似文献
10.
D J O''''Donoghue A Darvill F W Ballardie 《The Journal of clinical investigation》1991,88(5):1522-1530
The autoantigen(s) that we have previously described in human glomeruli, recognized in IgA nephropathy, has (have) been identified as mesangial cell in origin. Cultured mesangial cells expressed 48- and 55-kD components binding IgG isotype autoantibodies (IgG-MESCA) present in sera of patients with both IgA nephropathy and Henoch-Sch?nlein purpura (HSP). IgG-MESCA were not detected in sera of normals, or patients with other autoimmune-mediated glomerulonephritides: anti-glomerular basement membrane disease, Wegener's granulomatosis, or in IgM-mesangial proliferative disease. Binding specificity was proven by F(ab')2 studies in enzyme-linked immunosorbent assay (ELISA) and Western blotting, and there was no significant affinity of IgA or IgM immunoglobulins. Fluorescein isothiocyanate-conjugated IgG from ELISA-positive sera localized to the mesangium and peripheral capillary loops of glomeruli, supporting the belief that the antigen is expressed in normal human renal tissue. However, only about one third of mesangial cells in culture showed affinity for IgG from ELISA-positive sera, suggesting variable expression of the antigen(s) in vitro. The only autoantigen(s) present in glomeruli, and extractable from whole normal glomeruli by the techniques employed, localized on the mesangial cell. In both IgA nephropathy and HSP, autoimmunity was intermittently present, with fluctuating levels of IgG-MESCA detectable in sera. There were positive correlations with the degree of glomerular injury assessed by erythrocyturia and proteinuria in IgA nephropathy, but significance was reached with only the degree of hematuria in HSP. These findings suggest a contributing role in the pathogenesis of the mesangial proliferative lesions and demonstrate autoimmunity common to both IgA nephropathy and HSP. 相似文献
11.
G A Harff E T Backer 《Clinica chimica acta; international journal of clinical chemistry》1990,193(3):157-163
Variant electrophoretic patterns of lactate dehydrogenase isoenzymes were studied. By radial immunodiffusion and immunoelectrophoresis, immunoglobulin and light chain class of autoantibodies to lactate dehydrogenase were identified in nine sera: seven of these sera demonstrated IgG (5 lambda, 2 kappa) autoantibodies to lactate dehydrogenase, the other two demonstrated IgA (both kappa) autoantibodies to lactate dehydrogenase, the other two demonstrated IgA (both kappa) autoantibodies to lactate dehydrogenase. We conclude that radial immunodiffusion and immunoelectrophoresis are equally effective for identifying auto-antibodies to lactate dehydrogenase in serum. Radial immunodiffusion, however, is easier to perform than immunoelectrophoresis. 相似文献
12.
Antineutrophil Cytoplasmic Autoantibodies Interact with Primary Granule Constituents on the Surface of Apoptotic Neutrophils in the Absence of Neutrophil Priming 总被引:12,自引:0,他引:12 下载免费PDF全文
Hannah M. Gilligan Brunel Bredy Hugh R. Brady Marie-Jose Hbert Henry S. Slayter Yuhui Xu Joyce Rauch Michael A. Shia Jason S. Koh Jerrold S. Levine 《The Journal of experimental medicine》1996,184(6):2231-2242
The pathogenic role of antineutrophil cytoplasmic autoantibodies (ANCA) remains controversial because of the difficulty in explaining how extracellular ANCA can interact with intracellular primary granule constituents. It has been postulated that cytokine priming of neutrophils (PMN), as may occur during a prodromal infection, is an important trigger for mobilization of granules to the cell surface, where they may interact with ANCA. We show by electron microscopy that apoptosis of unprimed PMN is also associated with the translocation of cytoplasmic granules to the cell surface and alignment just beneath an intact cell membrane. Immunofluorescent microscopy and FACS® analysis demonstrate reactivity of ANCA-positive sera and antimyeloperoxidase antibodies with apoptotic PMN, but not with viable PMN. Moreover, we show that apoptotic PMN may be divided into two subsets, based on the presence or absence of granular translocation, and that surface immunogold labeling of myeloperoxidase occurs only in the subset of PMN showing translocation. These results provide a novel mechanism that is independent of priming, by which ANCA may gain access to PMN granule components during ANCA-associated vasculitis. 相似文献
13.
Higgins RM; Goldsmith DJ; MacDiarmid-Gordon A; Taberner D; Venning MC; Ackrill P 《QJM : monthly journal of the Association of Physicians》1996,89(4):297-306
After serious paracetamol overdose, charcoal haemoperfusion was used to
remove paracetamol from the circulation, aiming to reduce the severity of
subsequent hepatic damage. Daily long-hours high-flux dialysis was given to
patients with grade III-IV hepatic encephalopathy, and also to those at
risk of developing encephalopathy. We reviewed patients treated in this
manner who had not received N-acetylcysteine within the first 15 h after
overdose. From January 1983 to January 1993, 73 patients with serious
paracetamol overdose were seen, of whom 51 received charcoal haemoperfusion
and/or high-flux dialysis. Patients who were admitted within the first 42 h
after overdose and who received haemoperfusion and/or dialysis had
significantly lower peak levels of prothrombin time, bilirubin and
creatinine than those who were admitted after 42 h. Mortality was also
lower amongst patients admitted before 42 h, at 2/18 (11%) vs. 15/33 (45%),
<it>p</it> < 0.05.
相似文献
14.
Warrell DA; Hudson BJ; Lalloo DG; Trevett AJ; Whitehead P; Bamler PR; Ranaivoson M; Wiyono A; Richie TL; Fryauff DJ; O'Shea MT; Richards AM; Theakston RD 《QJM : monthly journal of the Association of Physicians》1996,89(7):523-530
The New Guinea small-eyed or Ikaheka snake, <it>Micropechis
ikaheka</it>, which occurs throughout New Guinea and some adjacent
islands, is feared by the indigenes. The first proven human fatality was in
the 1950s and this species has since been implicated in many other cases of
severe and fatal envenoming. Reliable attribution of envenoming to this
species in victims unable to capture or kill the snake recently became
possible by the use of enzyme immunoassay. Eleven cases of proven
envenoming by <it>M. ikaheka</it>, with two fatalities, were
identified in Papua New Guinea and Irian Jaya. Five patients showed no
clinical signs of envenoming by other Australasian elapids: mild local
swelling, local lymphadenopathy, neurotoxicity, general myalgia,
spontaneous systemic bleeding, incoagulable blood and passage of dark urine
(haemoglobinuria or myoglobinuria). Two patients developed hypotension and
two died of respiratory paralysis 19 and 38 h after being bitten.
<it>In vitro</it> studies indicate that the venom is rich in
phospholipase A2, is indirectly haemolytic, anticoagulant and inhibits
platelets, but is not procoagulant or fibrinolytic. It shows predominantly
post-synaptic neurotoxic and myotoxic activity. Anecdotally, Commonwealth
Serum Laboratories' (CSL) death adder antivenom has proved ineffective
whereas CSL polyvalent antivenom may be beneficial. Anticholinesterase
drugs might prove effective in improving neuromuscular transmission and
should be tested in patients with neurotoxic envenoming.
相似文献
15.
目的 探讨免疫印迹法在不同自身免疫性表皮下大疱病(SABD)患者基底膜带自身抗体(BMZ抗体)分布情况及其在SABD诊断和鉴别诊断中的应用价值。方法 以热分离法制备的人真皮、表皮提取物作为抗原,免疫印迹法检测97例SABD患者血清中BMZ抗体与基底膜抗原结合情况。结果 不同SABD患者血清中存在结合不同真皮、表皮抗原的IgG型和(或)IgA型BMZ抗体。大疱性类天疱疮患者血清中IgG和(或)IgA 相似文献
16.
Pieter Vermeersch Karel Geboes Godelieve Mariën Ilse Hoffman Martin Hiele Xavier Bossuyt 《Clinica chimica acta; international journal of clinical chemistry》2010,411(13-14):931-935
BackgroundDetection of IgG antibodies against deamidated gliadin peptides (DGP) is more sensitive and more specific for celiac disease than detection of IgG antibodies against native gliadin. Our aim was to evaluate the technical performance and diagnostic accuracy of four commercial IgG anti-DGP assays.MethodsCommercial IgG anti-DGP assays from Euroimmun, Inova, Phadia and The Binding Site were evaluated and their diagnostic accuracy (sensitivity and specificity) compared to other serologic assays for celiac disease (3 IgA and 2 IgG anti-tTG assays, 1 IgA and 1 IgG anti-gliadin assay, 1 IgA anti-DGP assay). The study population consisted of 86 consecutive CD patients and 741 disease controls.ResultsThe technical performance (linearity, interference and imprecision) of the IgG anti-DGP assays was acceptable. The sensitivity of the IgG anti-DGP assays varied between 76.7% and 86.0% at the cut-off recommended by the manufacturer and between 74.4% and 86.0% at the cut-off that corresponded to a specificity of 98%. The specificity varied between 97.3% and 99.3%. The diagnostic accuracy of the IgG anti-DGP assays was comparable to the diagnostic accuracy of the IgA anti-tTG assays. The sensitivity of the IgG anti-DGP assays was significantly better than sensitivity of the IgG anti-tTG assays (p < 0.05) and the specificity was significantly better than the IgA and IgG anti-gliadin assays (p < 0.05).ConclusionsThe overall performance of the four IgG anti-DGP assays was acceptable and the diagnostic accuracy comparable to the three IgA anti-tTG assays. 相似文献
17.
Kai Kisand Kalle Kisand Vello Salupere Raivo Uibo 《International Journal of Clinical & Laboratory Research》1994,24(2):98-101
Summary Autoantibodies to the recently described mitochondrial autoantigen, pyruvate dehydrogenase, have been shown to be specific
for primary biliary cirrhosis. In the present study we describe enzyme-linked immunosorbent assays to detect antibodies of
IgG, IgA, and IgM classes reactive with pyruvate dehydrogenase. These assays showed high sensitivity (95%) and specificity
(100%) for primary biliary cirrhosis when evaluated in 28 patients with primary biliary cirrhosis, 59 disease controls, and
214 healthy persons. Quantitation of these autoantibodies by calculating the areas under the sera titration curves of 10 primary
biliary cirrhosis patients indicated that an increase in IgA antibodies to pyruvate dehydrogenase is related to more rapid
disease progression. 相似文献
18.
W. J. MAYET A. G. PRESS E. HERMANN R. MOLL M. MANNS K. EEW K. H. MEYER ZUM BÜSCHENFELDE 《European journal of clinical investigation》1990,20(5):516-524
The immunologic basis of inflammatory bowel disease has been the focus of interest of a series of studies on Crohn's disease and the process of immune sensitization at the gastrointestinal mucosal level is functionally poorly understood. To date only few contradictory reports concerning the incidence of autoantibodies in patients with this disease exist. The aim of this study was to investigate the sera drawn from 60 patients suffering from biopsy-proven Crohn's disease to evaluate the prevalence of autoantibodies against nuclear antigens and cytoskeletal proteins. Using standard methods, no anti-nuclear antibodies or antibodies to extractable nuclear antigens could be detected. All sera were also negative for antibodies to double-stranded DNA, anti-mitochondrial antibodies, and antibodies to gastric parietal cells. Using sensitive enzyme-linke immunosorbent assays with purified antigens and Western blotting with cytoskeletal proteins of human intestinal cells, the following antibodies could be demonstrated: cytokeratin 18 autoantibodies (IgG 20.0%; IgM 6.7%; IgA 13.3%), actin antibodies (IgG 36.7%; IgM 48.3%, IgA 26.7%), desmin antibodies (IgG 6.7%; IgM 15.08%; IgA 5.0%), vimentin antibodies (IgG 3.3%; IgM 16.7%; IgA 10.0%) and tropomyosin antibodies (IgG 3.3%; IgM 3.3%, IgA 5.0%). Statistically significant correlations could be found for levels of cytokeratin 18 antibodies (IgM-type) and the BEST index of activity, and for levels of desmin antibodies (IgM-type) and the van HEES index of activity. Highest levels could be measured for actin antibodies (IgG-type) in patients with isolated disease manifestation in the colon. The mechanism of induction of autoantibodies against cytoskeletal components in Crohn's disease still remains obscure. Unmasking of hidden antigens after cell injury during the inflammatory process of disease might lead to sensitization and antibody production. The pattern of antibodies in patients with Crohn's disease seems to be different compared with that of connective tissue diseases. 相似文献
19.
Newborn humans manifest autoantibodies to defined self molecules detected by antigen microarray informatics 下载免费PDF全文
Merbl Y Zucker-Toledano M Quintana FJ Cohen IR 《The Journal of clinical investigation》2007,117(3):712-718
Autoimmune diseases are often marked by autoantibodies binding to self antigens. However, many healthy persons also manifest autoantibodies that bind to self antigens, known as natural autoantibodies. In order to characterize natural autoantibodies present at birth, we used an antigen microarray (antigen chip) to analyze informatically (with clustering algorithms and correlation mapping) the natural IgM, IgA, and IgG autoantibody repertoires present in 10 pairs of sera from healthy mothers and the cords of their newborn babies. These autoantibodies were found to bind to 305 different, mostly self, molecules. We report that in utero, humans develop IgM and IgA autoantibodies to relatively uniform sets of self molecules. The global patterns of maternal IgM autoantibodies significantly diverged from those at birth, although certain reactivities remained common to both maternal and cord samples. Because maternal IgG antibodies (unlike IgM and IgA) cross the placenta, maternal and cord IgG autoantibodies showed essentially identical reactivities. We found that some self antigens that bind cord autoantibodies were among the target self antigens associated with autoimmune diseases later in life. Thus, the obviously benign autoimmunity prevalent at birth may provide the basis for the emergence of some autoimmune diseases relatively prevalent later in life. 相似文献
20.
Nonopsonic antibodies in cystic fibrosis. Pseudomonas aeruginosa lipopolysaccharide-specific immunoglobulin G antibodies from infected patient sera inhibit neutrophil oxidative responses. 总被引:5,自引:0,他引:5 下载免费PDF全文
I Eichler L Joris Y P Hsu J Van Wye R Bram R Moss 《The Journal of clinical investigation》1989,84(6):1794-1804
Antibody opsonins from cystic fibrosis (CF) patients were investigated using nonmucoid and mucoid lipopolysaccharide (LPS) immunotype 1 Pseudomonas aeruginosa as bacterial ligands and PMN phagocytes. CF sera were compared to normal sera, polyvalent PA LPS hyperimmune globulin, and isotype switch variant monoclonal antibodies (MAbs) specific for type 1 PA LPS. Sera from PA-infected CF patients (CF PA+) had elevated levels of PA LPS and alginate IgG antibodies and promoted significantly greater antibody-dependent PMN chemiluminescence responses than sera from uninfected CF patients (CF PA-) or normal human sera (NHS). After adjustment for autologous IgG PA LPS antibody content, however, CF PA+ sera had less antibody-dependent opsonic activity than sera from CF PA- patients (P less than 0.025) or NHS (P less than 0.0025), suggesting qualitative opsonic defects of IgG PA LPS antibodies in CF PA+ sera. Antigen-specific immunoprecipitation of PA LPS antibodies enhanced opsonization by 40% of CF PA+ sera while uniformly reducing that from CF PA- sera (P less than 0.01), indicating LPS-specific nonopsonic antibodies in some CF PA+ sera. Alginate antibodies were not critical opsonins in most uninfected CF patient sera. PA LPS IgG antibodies isolated by immunoaffinity chromatography from NHS, hyperimmune globulin, and CF PA- sources were opsonic and had greater activity at equal antigen-binding concentration than identical antibodies isolated from infected CF patients (P less than 0.01-0.05); the majority of isolates from CF PA+ sera did not promote PMN oxidative responses above nonopsonic baseline. A potential isotypic basis for these findings was supported by differences in PMN responses to PA opsonized with MAbs of identical specificity but differing isotypes. PA LPS-specific IgG antibodies inhibiting PMN oxidative responses in infected patient sera demonstrate antigen-specific immunomodulation of host responses by chronic bacterial parasitism in CF, which may play a role in the pathophysiology of lung disease. 相似文献