Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; APS-1) is an autosomal recessive autoimmune disease, caused by mutations in the AIRE (autoimmune regulator) gene. Due to the proposed role of AIRE in central immune tolerance, the immune investigation of four females diagnosed with APECED, their siblings, parents and 14 age-matched controls was performed. The parameters analyzed included immunoglobulins, autoantibodies, cellular immunity and production of cytokines IFNgamma, IL-4 and IL-10, reflecting Th1xTh2 balance. Low IFNgamma levels (455 +/- 191 pg/ml) were detected in all affected girls compared to controls (910 +/- 406 pg/ml). Two girls with homozygous R257X mutations showed similarly marked elevation of IgM and increase of CD3+CD4+ lymphocytes. Positive autoantibodies against smooth muscle were found in one affected girl; another girl and her mother had antibodies against gastric parietal cells. Interestingly, all fathers had dramatically elevated levels of IgA and activated T lymphocytes. High frequency of abnormal immune results among parents is a novel finding which might suggest a subclinical immune deficit in heterozygotes with AIRE mutations.

• MeSH
• autoimunitní polyglandulární syndromy genetika   imunologie   MeSH
• autoprotilátky krev   MeSH
• dítě MeSH
• dospělí MeSH
• heterozygot MeSH
• imunoglobulin A krev   MeSH
• interferon gama biosyntéza   MeSH
• lidé MeSH
• mladiství MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• imunoglobulin A MeSH
• interferon gama MeSH

Deficiencies in adhesion molecules or their counter-receptors in humans may have severe consequences as exemplified by leukocyte adhesion deficiency (LAD) I or II syndromes. Because such diseases occur with great rarity, animal models are valuable for studying the role of particular adhesion molecules and their natural ligands in immunity. We studied selected immune parameters and general health in mice with a defect in the sialyl-Lewis X antigen (selectin ligand) caused by disruption of the gene encoding alpha(1,3)fucosyltransferase VII (Fuc-TVII). Leukocytes from Fuc-TVII -/- and control mice were tested for adherence to cellophane membranes or polymer particles in vivo and phagocytic activity in vitro. While no difference in adherence was found, the number of neutrophil granulocytes in exudate induced by intraperitoneal injection of polymer beads was reduced in knock-out mice. Moreover, the phagocytic activity in Fuc-TVII -/- mice was significantly reduced. These animals have splenomegaly due to increased hematopoiesis and reduced weight but do not exhibit clinical signs of immunodeficiency. In conclusion, the lack of Fuc-TVII activity leads to several morphological and functional abnormalities without an impact on survival rate.

• MeSH
• buněčná adheze MeSH
• buňky kostní dřeně patologie   MeSH
• Candida albicans * MeSH
• celofán MeSH
• fagocytóza genetika   fyziologie   MeSH
• fukosyltransferasy nedostatek   genetika   MeSH
• LAD syndrom krev   genetika   MeSH
• membrány umělé MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši inbrední DBA MeSH
• myši knockoutované MeSH
• myši MeSH
• neutrofily mikrobiologie   fyziologie   MeSH
• slezina patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• celofán MeSH
• fukosyltransferasy MeSH
• galactoside 3-fucosyltransferase MeSH Prohlížeč
• membrány umělé MeSH

Henoch-Schönlein purpura is the most common vasculitis of childhood, accompanied by the deposition of IgA1 immunoglobulins into the glomerular mesangium. The actual molecular mechanism of IgA deposition is not clear, but the altered glycosylation of O-linked oligosaccharides of the hinge region of IgA1 is generally considered as the crucial etiopathogenic factor. The oligosaccharides of this glycoprotein from healthy persons are principally of mucin-type Galbeta1,3GalNAcalpha-O-glycan core structure, frequently sialylated. The patient's IgA hinge region saccharide is an incomplete GalNAcalpha-O-glycan only. This study investigates the presence of binding sites for alpha-GalNAc and beta-GalNAc in frozen sections of kidney with and without nephropathy prompted by the possibility for a lectin mechanism of IgA deposition to mesangium. Neoglycoproteins prepared as conjugates with derivatized alpha- or beta-GalNAc moieties as histochemically crucial ligands and biotinylated bovine serum albumin as a carrier were employed for this purpose. The result of the experiments demonstrated expression of specific and accessible binding sites for both alpha- and beta-GalNAc in tubules but not in glomeruli of kidney samples both with and without nephropathy. These findings imply no involvement of a lectin mechanism of IgA1 binding to mesangium, unless a temporary alteration of accessibility of binding sites for probes in glomeruli occurs or the linkage region beyond the monosaccharide is pivotal for a receptor whose binding site may accommodate a peptide epitope in addition to the O-linked alpha-GalNAc residue.

• MeSH
• acetylgalaktosamin metabolismus   MeSH
• dítě MeSH
• glomerulární mesangium metabolismus   patologie   MeSH
• glykosylace MeSH
• IgA nefropatie etiologie   metabolismus   MeSH
• IgA vaskulitida komplikace   MeSH
• imunoglobulin A chemie   metabolismus   MeSH
• ledvinové kanálky metabolismus   patologie   MeSH
• ledviny metabolismus   patologie   MeSH
• lidé MeSH
• nádory ledvin chemie   patologie   MeSH
• posttranslační úpravy proteinů MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zmrazené řezy MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• acetylgalaktosamin MeSH
• imunoglobulin A MeSH

BACKGROUND: Henoch-Schönlein purpura is a common vasculitis of childhood affecting the skin, joints, gastrointestinal tract, and kidney. The mesangial deposition of IgA1 is the most critical factor for the prognosis of patients with this disease. The aberrant glycosylation of the IgA1 subclass with the absence of terminally located galactose and presence of only alpha-N-acetylgalactosamine in O-linked oligosaccharides in the hinge region of IgA1 represents a prominent difference from the normal IgA1. These alterations prompt the supposition that the sugar part may guide IgA deposition by recognition of endogenous lectins on the mesangium. METHODS: Owing to the limited knowledge about the expression of carbohydrate-binding sites in the human kidney we initiated the study of this aspect with a class of tools which are suitable to map the lectinome of cells. Employing biotinylated neoglycoconjugates, glycosaminoglycans, and sulphated polysaccharides we monitored the presence of accessible carbohydrate-binding sites in control kidneys represented by tumour-free areas of kidneys with Grawitz tumour and in biopsies from patients with Henoch-Schönlein purpura-associated IgA nephropathy. RESULTS: Using frozen sections, no expression of any tested carbohydrate-binding site(s) was observed in the endothelial and the mesangial cells in glomeruli of the control kidneys as well as in the biopsies from Henoch-Schönlein purpura IgA nephropathic kidneys, in contrast to the tubules. The N-acetylgalactosamine-binding sites were expressed only in the inner layer of Bowman's capsule of 20% of glomeruli of the control kidney from one patient with Grawitz tumour and one biopsy from a patient with Henoch-Schönlein purpura-associated IgA nephropathy. However, the macrophages in the glomeruli of patients with IgA nephropathy and interstitial macrophages from both studied groups, i.e. without and with IgA nephropathy, harbour capacity to recognize carrier-immobilized alpha-N-acetylgalactosamine. Access to this binding site for the neoligand conjugate can be blocked by the monoclonal antibody MEM-18 recognizing CD14 antigen. CONCLUSION: The possibility for a participation of macrophage deposition of IgA1 in mesangium via a lectin mechanism involving this binding capacity warrants further studies.

• MeSH
• acetylgalaktosamin metabolismus   MeSH
• antigeny CD14 metabolismus   MeSH
• IgA nefropatie etiologie   MeSH
• IgA vaskulitida etiologie   MeSH
• imunoglobulin A metabolismus   MeSH
• ledviny metabolismus   MeSH
• lidé MeSH
• metabolismus sacharidů * MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylgalaktosamin MeSH
• antigeny CD14 MeSH
• imunoglobulin A MeSH

OBJECTIVE: Primary Sjögren's syndrome (pSS) in childhood is a rare disease. Diagnostic criteria are available for adult patients only. In order to establish diagnostic criteria for juvenile pSS an analysis of 7 girls and one boy suffering from pSS with early onset is reported. Due to the rarity of the disease, data on patients with pSS reported in the literature are included in the proposal for modified diagnostic criteria. METHODS: The diagnosis of pSS was established according to the criteria for adulthood pSS, duly modified, which include clinical symptoms and laboratory immunological evaluation. RESULTS: The average age of our patients at clinical onset was 13.5 years (range: 10-17 yrs.). Clinical signs included systemic (fever, fatigue) as well as local (parotitis, vulvovaginitis, conjunctivitis) symptoms. Paralysis due to hypokalemia linked to renal tubular acidosis and central nervous system (CNS) involvement was seen in one patient. Asymptomatic renal tubular acidosis was diagnosed in another 2 patients. Autoimmune hepatitis was present in 2 patients. All patients had laboratory abnormalities: hyperimmunoglobulinemia IgG, high titers of antinuclear antibodies (anti-SS-A and/or anti-SS-B) and elevated serum amylases. Sicca syndrome was never seen during childhood, although it developed later in 3 patients, after 7 to 10 years of follow-up. CONCLUSIONS: It has been stressed that the classical diagnostic criteria for adult Sjögren's syndrome, especially sicca syndrome, are not applicable to a pediatric onset of the disease. On the other hand, the presence of typical laboratory abnormalities can allow the diagnosis of these patients in the early stages. Both laboratory and clinical symptoms typical for childhood are included in our proposal for diagnostic criteria applicable to juvenile pSS. Life-threatening conditions such as hypokalemic paralysis, CNS involvement and hepatitis may also occur in children. Sicca syndrome tends to develop much later in pediatric patients.

• MeSH
• autoprotilátky krev   MeSH
• dítě MeSH
• hypergamaglobulinemie krev   MeSH
• imunoglobulin G krev   MeSH
• lidé MeSH
• mladiství MeSH
• revmatoidní faktor metabolismus   MeSH
• Sjögrenův syndrom krev   diagnóza   MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• imunoglobulin G MeSH
• revmatoidní faktor MeSH

Antineutrophil autoantibodies reacting with cytoplasmic antigens are associated with various types of vasculitides, whereas antibodies reacting with neutrophil membrane antigens are mostly related to autoimmune neutropenias. The aim of this study was the investigation of the effect of monoclonal antibodies (MoAbs) reacting with surface and cytoplasmic antigens of polymorphonuclear leukocytes (PMN) known to be targets for autoantibodies in human diseases. Blood of healthy volunteers was tested for several phagocytic functions in the presence of MoAbs against surface (CD16, CD11b, CD18, NB1) and cytoplasmic (proteinase 3; PR3) molecules. Candidacidal activity was significantly inhibited in the presence of all MoAbs but isotypic control. Phagocytic activity was inhibited by anti-CD11b and/or anti-CD18 MoAbs. Zymosan-induced chemiluminescence was reduced by MoAbs anti-CD16, CD18, and NB1, enhanced by anti-PR3 MoAb, and less enhanced by anti-CD11b. In conclusion, antimembrane antibodies diminished phagocytic functions at multiple steps; in contrast, anticytoplasmic MoAb promoted activation of oxidative burst in addition to impairment of microbicidal activity. This fact may be related to different pathogenic aspects of diseases associated with antimembrane and anticytoplasmic antibodies.

• MeSH
• antigeny CD18 imunologie   MeSH
• antigeny povrchové imunologie   MeSH
• autoantigeny imunologie   MeSH
• autoimunita imunologie   MeSH
• autoprotilátky imunologie   metabolismus   MeSH
• Candida albicans imunologie   MeSH
• cytoplazma imunologie   metabolismus   MeSH
• fagocytóza účinky léků   imunologie   MeSH
• lidé MeSH
• luminiscenční měření MeSH
• makrofágový antigen 1 imunologie   MeSH
• monoklonální protilátky imunologie   farmakologie   MeSH
• neutrofily imunologie   metabolismus   MeSH
• reakce antigenu s protilátkou MeSH
• receptory IgG imunologie   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD18 MeSH
• antigeny povrchové MeSH
• autoantigeny MeSH
• autoprotilátky MeSH
• makrofágový antigen 1 MeSH
• monoklonální protilátky MeSH
• receptory IgG MeSH