PubMed Health⌕ Search

Biomedical subjects

G Fontan

Publications and source records attributed to G Fontan.

At least 19 recordsLinked to original sources
PubMed2003

Epistatic effects occurring among susceptibility and protective MHC genes in IgA deficiency.

Immunoglobulin A deficiency (IgAD), the most prevalent primary immunodeficiency in Caucasian populations, shows strong evidence of polygenic inheritance with several associated genes being located in the major histocompatibility complex (MHC). Our aims were to determine which previously described MHC associations were primary and not secondary to a decrease or an increase in other MHC haplotype frequencies, to study the genetic interactions between all disease-associated MHC haplotypes and, finally, to ascertain the relative importance of protection vs susceptibility. A relative predispositional effect (RPE) study showed that in addition to the primary positive association of IgAD with HLA-DRB1*0102, DR3/TNFa2b3, and DR7 carrying haplotypes, DRB1*1501 was a marker of a primary protective factor in the Spanish population. Our data also indicate that the combined presence in an individual of two MHC susceptibility haplotypes notably increases the predisposition to the disease and that DRB1*1501 positive haplotypes eliminate the susceptibility conferred by any other MHC haplotype.

Alleles↗
PubMed2000

Tumor necrosis factor genomic polymorphism in Spanish IGA deficiency patients.

Selective IgA deficiency (IgAD) is the most common form of primary immunodeficiency. Its association with genes within the major histocompatibility complex (MHC) has been repeatedly reported. Recently the susceptibility gene has been located in the class III region, around the tumor necrosis factor (TNF) cluster. In this study we have examined IgAD association with TNF-alpha gene promoter polymorphisms and TNFa and b microsatellites. No significant association was found with the former polymorphisms and the observed associations with TNFa2 allele and haplotypes TNFa2b1 and TNFa2b3 were proven to be secondary to their occurrence on the B14-DR1 and B8-DR3 haplotypes, previously reported to be associated with susceptibility to IgAD. However, a primary negative (protective) association was found between the TNFa10 allele and IgAD.

Alleles↗
PubMed1999

HLA class II homozygosity confers susceptibility to common variable immunodeficiency (CVID).

Most cases of CVID occur sporadically, but familial cases do also occur and 15% of the patients with the disease have first degree relatives with IgA deficiency (IgAD). Our purpose was to study CVID association with HLA class II alleles and to ascertain whether this disease shares a common genetic background with IgAD in our population. Patients with CVID (n = 42), were typed using gene amplification and sequence-specific oligonucleotide probing for HLA-DRB1, DRB3, DQA1 and DQB1 loci and their typing compared with that of 96 IgAD and 334 healthy controls. We observed a positive association between non-Asp residues at position 57 of the HLA-DQbeta chain and CVID, although much weaker than in IgAD. Further, we found an association between CVID and homozygosity for genes encoding HLA class II molecules, especially HLA-DQ, not seen in IgAD. The data support the hypothesis that a restricted diversity of HLA class II molecules may contribute to susceptibility to CVID.

Alleles↗
PubMed1997

Soluble interleukin 6 (IL-6) receptor and IL-6 levels in serum and synovial fluid of patients with different arthropathies.

OBJECTIVE: We studied interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6R) in serum and synovial fluid (SF) to investigate their role in different arthropathies. METHODS: IL-6 was measured by ELISA and bioassay and sIL-6R by ELISA, in 210 sera and 73 SF samples from 49 patients with rheumatoid arthritis (RA), 20 crystal deposition disease, 17 osteoarthritis (OA), 24 with other inflammatory arthropathies, and 100 controls. In all patients, disease activity was assessed by erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); in patients with RA and other arthropathies pain, tender and swollen joints, and Ritchie index were also evaluated. Total leukocyte count in SF was determined. RESULTS: There was good correlation between IL-6 ELISA and bioassay levels both in serum (r = 0.62, p = 0.0001) and in SF (r = 0.72, p = 0.0001). Serum IL-6 was detected only in patients with inflammatory arthritis and SF IL-6 was detected in all patient groups. Serum IL-6 correlated with swollen joints (r = 0.35, p = 0.05), ESR (r = 0.46, p = 0.001), and CRP (r = 0.46, p = 0.001) in RA; and with CRP (r = 0.89, p = 0.0001) in crystal deposition disease. SF IL-6 correlated with ESR (r = 0.54, p = 0.007) and CRP (r = 0.42, p = 0.04) in RA; with SF total leukocyte count (r = 0.61, p = 0.004) in crystal deposition disease; and with SF total leukocyte count (r = 0.61, p = 0.009) in OA. No correlations were found in the group with other inflammatory diseases. No correlations were found between sIL-6R and IL-6 or between sIL-6R and disease activity variables in any group of patients. CONCLUSION: Unlike IL-6, sIL-6R is not produced at the site of inflammation and is not related to clinical or biological disease activity variables. Only in RA are both IL-6 and sIL-6R levels increased, suggesting that sIL-6R may reinforce the systemic effects of IL-6.

Arthritis↗
PubMed1994

Identification of deletions in the btk gene allows unambiguous assessment of carrier status in families with X-linked agammaglobulinaemia.

Mutations within the btk gene have recently been shown to cause X-linked agammaglobulinaemia (XLA). Altered patterns of DNA restriction fragments are seen by Southern blot analysis of DNA from affected patients with deletions in the btk gene. We have identified seven affected families in which altered restriction fragments can be used to diagnose and confirm the carrier status of female relatives of affected boys and in prenatal diagnosis.

Agammaglobulinemia↗
PubMed1993

Characterization of minor and major antigenic regions within the hepatitis B virus nucleocapsid.

Hepatitis B core antibodies (anti-HBc) appear very early during the course of the hepatitis B virus infection and often persist years after viral clearance. In order to characterize the immunodominant domain of the HBcAg, the human immune response against the HBV nucleocapsid (HBcAg) was analyzed by using 14 synthetic peptides. Anti-HBc antibodies were detected by an indirect enzyme-linked immunosorbent assay (ELISA) with HBc peptides. Results suggest that the anti-HBc response is heterogeneous and directed against the whole primary structure of the HBc protein. Results also indicate that the epitopes recognized by anti-HBc antibodies can vary with the stages of the disease. In most sera from patients with serological evidence of acute HBV infection, anti-HBc antibodies recognized all the HBc peptides; conversely, after the acute phase, anti-HBc antibodies recognized predominantly epitopes located within the central region of the HBc protein from residue 74 to 123. Our results suggest that the HBV core protein is made up of two antigenic regions: a major one expressing a family of immunodominant epitopes from residue 74 to 123, whereas the minor encompasses the rest of the protein. The concept of the conformational nature of the unique HBcAg determinant is discussed, suggesting numerous families of linear epitopes.

Amino Acid Sequence↗
PubMed1992

Combined total deficiency of C7 and C4B with systemic lupus erythematosus (SLE).

The first inherited combined total deficiency of C7 and C4B complement components associated with SLE is described in a young female. Functional C7 assays showed a homozygous C7 deficiency in the propositus and her sister, and an heterozygous one in their parents. C4 molecular analyses showed that both the propositus and her mother had two HLA haplotypes carrying only C4A-specific DNA sequences and a normal C4 gene number. Thus, only C4A proteins could be expressed, with resultant normal C4 serum levels. The coexistence of a combined complete C7 and C4B deficiency may therefore abrogate essential functions of the complement cascade presumably related to immune complex handling and solubilization despite an excess of circulating C4A. These findings challenge the putative pathophysiological roles of C4A and C4B and stress the need to perform both functional assays and C4 allotyping in patients with autoimmune pathology and low haemolytic activity without low serum levels of a classical pathway complement component.

Adult↗
PubMed1990

Large fragments of nef-protein and gp110 envelope glycoprotein from HIV-1. Synthesis, CD analysis and immunoreactivity.

Chemical synthesis of large peptide fragments (from 18 to 66 amino acid residues long) of the gp110 envelope glycoprotein and of nef-protein from HIV-1 was achieved by the solid phase method. Stepwise assembling of the peptide chains was carried out automatically on 4-(oxymethyl)-phenylacetamidomethyl resin using the N-alpha-butyloxycarbonyl amino acids with benzyl-based side chain protecting groups. Two elongation protocols were used depending on the peptide chain length: a standard cycle, mainly characterized by a single coupling step (Boc-amino acid symmetrical anhydride in dimethylformamide), and an optimized one for large peptides, based on a double coupling strategy (Boc-amino acid symmetrical anhydride first in dimethylformamide, then in dichloromethane). Final cleavage of the peptide from the solid support was carried out by anhydrous hydrogen fluoride and crude peptides were purified by C18 reverse phase medium pressure liquid chromatography after molecular filtration. Characterization of the purified peptides was done by analytical HPLC, amino acid content determination, and circular dichroism analysis both in polar (H2O) and in non-polar (TFE) environments. Immunoreactivity of anti-nef positive sera from HIV-1 infected patients by ELISA with the synthetic peptides was investigated. The results showed four major antigenic regions of nef-protein and mainly the immunodominance of the N- and C-termini of the molecule. Several of these peptides should prove to be useful for both diagnosis and vaccination purposes.

Amino Acid Sequence↗
PubMed1989

Identification of a common domain in calmodulin-activated eukaryotic and bacterial adenylate cyclases.

Bordetella pertussis and Bacillus anthracis, two taxonomically distinct bacteria, secrete adenylate cyclase toxins that are activated by the eukaryotic protein calmodulin. The two enzymes contain a well-conserved stretch of 24 amino acid residues [Escuyer et al. (1988) Gene 71, 293-298]. Antibodies have been obtained against two synthetic heptadecapeptides, covering part of the conserved sequences. The anti-peptide antibodies specifically reacted in Western blots with the rat brain adenylate cyclase as well as with the two bacterial enzymes. Anti-rat brain adenylate cyclase serum contained antibodies that were retained by the immobilized peptides, and the affinity-purified antibodies yielded the same recognition pattern of the eukaryotic enzyme as did the unfractionated serum. These results indicate that the eukaryotic adenylate cyclase contains an epitope closely related to that specified by the conserved bacterial sequence. The synthetic peptides and the bacterial adenylate cyclases appeared to compete for ATP (KD of the ATP-peptide complex ca. 0.2 mM), suggesting that the conserved sequence may be part of the substrate binding site in these two enzymes.

Adenylyl Cyclases↗
PubMed1989

Use of synthetic peptides for the detection of antibodies against the nef regulating protein in sera of HIV-infected patients.

Human sera were tested for the presence of anti-nef antibodies by radioimmunoassay (RIA), with recombinant radiolabelled nef expressed in E. coli. Of the 300 HIV-positive sera tested by RIA, 70 +/- 5.3% were found to be anti-nef positive. Anti-nef antibodies bound to nef with a high affinity (K 0.5 = 2.2 x 10(-9) M). In 31 of the sera, the specificity of anti-nef antibodies was further analysed by enzyme-linked immunosorbent assay (ELISA) with large synthetic peptides ranging from 31 to 66 amino acid residues and spanning the total sequence of nef from HIV-1. The results obtained showed that the immunodominant antigenic sites of nef were located close to the N- and C-terminal regions of the molecule.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Anti-IgA antibodies in selective IgA deficiency and in primary immunodeficient patients treated with gamma-globulin.

Sera from 106 blood donors, 40 patients with primary immunodeficiencies (ID) treated with gamma-globulin, and 46 patients with selective IgA deficiency were analyzed by an enzyme-linked immunosorbent assay for anti-IgA antibodies. Increased levels of antibodies to IgA were found in 5.6% of the blood donors, 17.5% of the ID patients, and 36.8% of the isolated IgA deficiencies. The percentage was higher in patients with IgA and IgG2 deficiencies (50%). The percentage of patients having increased levels of anti-IgA antibodies was similar to the total prevalence of the 10 other autoantibodies studied. These anti-IgA antibodies were mainly of the IgG class, except from one blood donor with IgM antibodies, and two patients, one with isolated IgA deficiency and the other with common variable immunodeficiency who had anti-IgA antibodies of the IgE class. The latter patient developed a near fatal anaphylactic reaction when intravenous gamma-globulin was administered. Most of the patients with severe adverse reactions to gamma-globulin did not present anti-IgA antibodies. Our data suggest that at least in some immunodeficient patients the elevated amounts of anti-IgA antibodies are not related to the administration of exogenous IgA. The importance of measuring anti-IgA antibodies of the IgG and IgE isotypes in IgA-deficient patients as well as in patients in treatment with gamma-globulin is emphasized.

Adult↗
PubMed1982

Hereditary myeloperoxidase deficiency: study of 12 cases.

12 cases of hereditary myeloperoxidase (MPO) deficiency are reported. Histochemical stainings, lysosomal enzyme determinations, electron microscopic study of MPO and granulocytic function were performed. Family studies on 2 generations were carried out in 5 patients and histochemical stainings and biochemical lysosomal enzyme determinations were done. MPO deficiency was found to follow autosomal recessive inheritance and only rarely to have clinical effects.

Azo Compounds↗
PubMed1982

Inhibition of neutrophil migration by serum IgA from patients with IgA nephropathy.

Previously we showed that patients with IgA nephropathy present high serum levels of polymeric IgA and that in vitro polyclonal stimulation of their peripheral blood lymphocytes results in the synthesis of a large amount of true polymeric IgA. The aim of this study was to determine if the serum of patients with IgA nephropathy was capable of suppressing the directional migration of human normal polymorphonuclear cells (PMN), as do the polymeric fractions of IgA myeloma. Incubation of controls' PMN with fresh or heat-inactivated patients' plasma impaired the casein-induced directional migration significantly more than incubation with controls' plasma. This inhibitory effect was closely linked to polymeric IgA fractions and to a lesser extent with monomeric IgA immune complexes. The removal of IgA by immunoadsorption from patients' plasma completely abolished the migration suppression observed on controls' PMN. These results suggest that the high serum levels of polymeric IgA observed in patients with IgA nephropathy, by inhibiting directional migration and phagocytosis of PMN, and probably monocytes, could facilitate the persistent circulation and renal deposition of immune complexes.

Chemotaxis, Leukocyte↗
PubMed1982

Functional assessment of T and B lymphocytes in patients with selective IgM deficiency.

Two patients with selective IgM deficiency were studied. Both presented with dermatitis, chronic diarrhoea, recurrent respiratory infections, failure to thrive, elevated serum IgE levels and in vivo impairment of antibody production. No phagocytic or complement abnormalities were found. B lymphocytes with surface IgM were present in normal or high percentage in peripheral blood, and produced normal amounts of IgM in vitro when co-cultured with normal T cells. Patients' T cells did not show excess suppressor function in vitro but had a decreased helper activity for IgM, IgG and IgA production. It is suggested that both patients have an extensive humoral immune deficiency that might be caused by the immunoregulatory T cell defect.

B-Lymphocytes↗
PubMed1981

Ataxia-telangiectasia (A-T). Contribution with eighteen personal cases.

Eighteen patients with ataxia-telangiectasia are presented. They belong to only one series. They are 7 males and 11 females aged between 17 months and 12 years. All of them presented the usual signs of the illness. There was more than one sibling affected in three families, in one of them three brothers and one second cousin of theirs. The immunological studies showed a deficit of IgA in 13 cases and an absence of IgG in one case. Six children died, one of which suffered from lymphosarcoma. The other appear to have died of infectious respiratory problems. The clinical picture deteriorated progressively in the majority of the cases, although in some of them a halt in the progression of the illness was observed for some time.

Antibody Formation↗