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J M Saint-Remy

Publications and source records attributed to J M Saint-Remy.

66 records · Page 4Linked to original sources

Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. V. Auto-anti-idiotypic antibody characterization and cross-reactivity.

From the serum of 10 allergic subjects we have prepared IgG antibodies recognizing idiotopes carried by specific antibodies to Dermatophagoides pteronyssinus (Dpt) allergens, and studied cross-reactivity of anti-Dpt IgG bystander and antigen-binding site-associated idiotopes by latex agglutination assays. Idiotopes of specific anti-Dpt IgE were evaluated by radioimmunoassays. Depending on the assay, a binding or inhibition of more than 50%, as compared to the reactivity of specific antibodies with the corresponding anti-idiotypic (anti-Id) IgG, was considered significant. Cross-reactivity of antigen-binding site-associated idiotopes attained a mean proportion of 6/10 for IgG and 9.6/10 for IgE. By contrast, bystander idiotopes cross-reacted only occasionally with a mean proportion of 2/10 for both IgG and IgE antibodies. Anti-Id antibodies from two subjects have been isolated by adsorption on insolubilized anti-Dpt antibodies of the corresponding patient. Using this purified material we have confirmed that (a) the majority of anti-Id antibodies carry an "internal image" of the initial antigen and compete in a dose-dependent manner with Dpt allergens for the binding to the anti-Dpt antibodies and (b) paratope-associated idiotopes of anti-Dpt antibodies are shared by unrelated individuals.

Allergens↗

Latex allergosorbent test (LAST): a new immunoassay for specific IgE with latex particles.

We describe a two-step latex (Lx) agglutination assay for the titration of specific anti-Dermatophagoides pteronyssinus IgE. The samples are first incubated with allergen-coated Lx of 2.3 microns diameter. Bound IgE is digested by pepsin and then titrated by its agglutinating activity on 0.8 micron Lx particles coated with antihuman Fc epsilon rabbit F(ab')2. This latex allergosorbent test detects 100 pg of specific IgE per milliliter and does not depend on the concentration of total IgE. Owing to a tenfold increase in the allergosorbent surface, no competition with the binding of specific anti-D. pteronyssinus IgG is observed. Pepsin digestion eliminates potential interferences caused by autoantibodies against IgE. A good correlation (r = 0.92) is found with Phadebas RAST on a series of 91 samples. The latex allergosorbent test does not make use of radioisotopes and can be performed in less than 6 hours.

Animals↗

Human immune response to allergens of house dust mite, Dermatophagoides pteronyssinus. Isotypic analysis of antibodies in atopic and non-atopic subjects.

Specific antibodies isolated by immunoabsorption on four main insolubilized allergens from Dermatophagoides pteronyssinus (DPT) had the following isotypic distribution: in 16 atopic patients, 52% IgG, 40% IgM, 8% IgA, 0.1% IgE and, in 12 non-atopic individuals, 48% IgG, 46% IgM, 6% IgA, 0.03% IgE. The ratios between geometric means of antibody values in each class (atopic vs non-atopics) were 2.4 for IgG, 2.0 for IgM, 2.8 for IgA and 66.7 for IgE. The amount of anti-DPT antibodies in IgG subclasses did not follow the usual distribution of total IgG subclasses, i.e., IgG1 greater than IgG2 greater than IgG3 greater than IgG4. In atopics the order was IgG2 greater than IgG1 greater than IgG4 greater than IgG3 and in non-atopics, IgG4 greater than IgG1 = IgG2 greater than IgG3 although 6/12 of the latter had no detectable (less than 0.5 micrograms/ml plasma) IgG4.

Adult↗

The human immune response against major allergens from house dust mite, Dermatophagoides pteronyssinus. II. Idiotypic cross-reactions of allergen-specific antibodies.

Antisera were prepared in rabbits against the idiotypic (Id) determinants of antiallergen antibodies. These antibodies were isolated from the plasma of 10 unrelated patients by immunoabsorption. Three major allergens isolated from the house dust mite, Dermatophagoides pteronyssinus (DPT), were used. The anti-Id antisera were rendered specific by successive absorption on insolubilized allergens, IgG and IgM from a pool of human sera and Ig from the donor after removal of anti-DPT antibodies by absorption. Anti-Id antibodies raised essentially against IgG antibodies were found to inhibit the agglutinating activity of both IgG and IgM anti-DPT antibodies toward allergen-coated latex. These anti-Id antibodies were also able to inhibit partly the binding of radiolabeled allergen to IgE anti-DPT antibodies. Matching the anti-Id antisera with the various individual anti-DPT antibodies revealed an Id cross-reactivity of about 71% for IgG, 61% for IgM and 62% for IgE. A second and predominant type of anti-Id antibodies recognized bystander idiotopes as the allergen did not inhibit Id-anti-Id reaction. These idiotopes were apparently more specific to individuals (private) as the anti-DPT antibodies of a given patient did not agglutinate latex particles coated with anti-Id antibodies prepared against Id of another patient.

Allergens↗

Effect of age-dependent enzymatic degradation of zymosan into oligosaccharides during incubation with serum on its opsonization by complement.

Incubation of zymosan particles with serum was shown to be accompanied by their partial breakdown into the oligosaccharides maltose, maltotriose, and maltotetraose, that were quantified under the form of glucose after degradation by alpha-glucosidase. Incubation with normal adult serum yielded twice as much glucose than incubation with cord serum. The degradation of zymosan could be mimicked by incubation with purified pancreatic alpha-amylase. A correlation was also found between the amount of oligosaccharides released from the particles during their incubation with serum and the concentration of amylase in the sera. The latter is low in newborns and increases several-fold, to nearly adult levels, at 3-6 months of age. Preincubation of zymosan with purified pancreatic alpha-amylase resulted in an approximately 50% increase in the binding of radioactive anti-C3c in the supernates obtained after subsequent incubation with cord serum but not with adult serum. With six of 24 cord sera, but not with adult serum, it also resulted in an augmentation of the chemiluminescence accompanying the phagocytosis of the particles after their opsonization. It is concluded that the relative inefficiency of cord and newborn serum in opsonizing zymosan is attributable not only to their lower content of the components of the alternative pathway of complement, but also to a lower concentration of serum amylase.

Adult↗

Mechanism of activation of the classical pathway of complement by monoclonal IgE (DES). Restricted regulation of C4b by C4b-binding protein.

A human monoclonal IgE from patient DES, IgE (DES), has been shown to activate the classical pathway of complement. The mechanism of this activation has been investigated and can be summarized as follows: (a) IgE (DES) is able to bind and activate C1 in a dose-dependent fashion. This activation increases with the size of the aggregates used, but the affinity of C1 for IgE (DES) is weaker than for IgG. (b) A classical pathway C3 convertase can be assembled on IgE (DES) using purified C1, C4 and C2. The formation decay of this convertase is similar to that formed on IgG with an half-life of 9 min at 37 degrees C. (c) The extrinsic regulation of the C3 convertase by C4bp is restricted on IgE (DES) as compared to IgG. This restriction is shown on both the formation and the decay of the convertase. The mechanism of activation of the classical pathway of complement by IgE (DES) thus present some similarities with the assembly of the C3 convertase by the alternative pathway.

Antibodies, Monoclonal↗

Activation of the classical pathway of human complement by a human monoclonal IgE, IgE(DES).

Activation of the classical pathway of human complement by monoclonal IgE from patient DES was demonstrated by using IgE(DES) coupled to latex particles. This material depleted human serum of C1 and C4 hemolytic activities. In addition, C3bi was deposited in a calcium-dependent way onto the insolubilized IgE as shown by the agglutination of latex by conglutinin. The alternative pathway was also activated. These anticomplementary activities were dose and time dependent. Moreover, we confirmed that another monoclonal IgE, IgE(PS), activated the alternative pathway exclusively. Particular attention was paid to exclude contamination by other immunoglobulins or C-reactive protein, generation of artifacts due to the chemical coupling, and the presence of proteolytic enzymes in the IgE(DES) preparation. Moreover, evidence is also presented against the involvement of IgG or IgM anti-IgE autoantibodies that could activate the classical pathway after their binding to insolubilized IgE(DES). Although one cannot exclude the possibility that IgE(DES) or IgE(PS) are abnormal proteins, these findings suggest the existence of an isotypic or allotypic variation of IgE.

Animals↗

Defective activation of the alternative pathway of complement in two brothers with ataxia-telangiectasia.

Two brothers with ataxia-telangiectasia and recurrent respiratory tract infections are presented. Immunological investigations showed normal immunoglobulin levels (except for the absence of IgA in one child) with absence of haemagglutination inhibiting antibody response to inactivated influenza virus vaccine, normal total lymphocyte counts with decreased T cell numbers, absence of delayed hypersensitivity skin reaction to PPD, in vitro unresponsiveness of T lymphocytes to PHA with presence of a serum inhibitor able to depress normal lymphocyte transformation, and normal phagocytosis and killing of Staph. aureus by peripheral blood polymorphonuclear leucocytes. Complete complement screening revealed a non-functioning alternative pathway in both brothers. The presence of normal factor B lytic activity after isoelectrofocusing the serum and inhibition of the lytic activity of purified components with the patients' serum raised the possibility of a serum inhibitor. The nature of this was not elucidated but it may be one of the reasons why patients with ataxia-telangiectasia have an increased incidence of infections.

Ataxia Telangiectasia↗

Interactions of chrysotile asbestos fibres with the complement system.

Type A chrysotile fibres (white asbestos) were tested in vitro for activation of the complement system. Fibres were incubated in normal human serum (NHS), factor B-depleted human serum, and normal and C4-deficient guinea-pig sera; the supernates were assayed for the remaining complement activity. Activation of the alternative pathway (AP) was shown in three ways. First, quantitative measurement of factor B; second, kinetic analysis of rabbit red blood cell lysis in whole alternative pathway (AP) and factor B lytic assays; third, qualitative measurement of C3 and factor B conversion by crossed immunoelectrophoresis. No C3 convertase activity could be demonstrated on the fibres but other possible mechanisms of AP activation are discussed. Magnesium itself is not responsible for this activation because acid-treated fibres retain this property. The early classical pathway is not involved as shown by normal whole complement activity of a factor B-depleted human serum and the absence of decrease of C4 functional activity. Knowing that complement proteins are present in pulmonary alveoli, mainly provided by cell synthesis, we suggest that complement activation in vivo may be relevant to the genesis of the chronic inflammation and fibrosis in the lung.

Animals↗

An M(r) 145,000 low-density lipoprotein (LDL)-binding protein is conserved throughout the Kinetoplastida order.

In view of the importance of the low-density lipoprotein (LDL)-receptor in Trypanosoma brucei, we have examined whether other bloodstream trypanosomes of medical and veterinary importance (T.b. rhodesiense, T. equiperdum, T. vivax, T. congolense), but also related parasites developing in mammalian (Leishmania donovani) and non-mammalian hosts (Crithidia luciliae and Phytomonas sp. isolated from Euphorbia), would possess an LDL-receptor of their own. (1) All these parasites specifically accumulate human 125I-LDL with a relatively 2.5-fold higher rate for bloodstream trypanosomes. (2) A mixture of monoclonal antibodies raised against T.b. brucei LDL-receptor inhibit binding of LDL to all species but with different efficiency. (3) A single glycoprotein of similar M(r) (gp145) is isolated by LDL-affinity chromatography from all the above species, as well as from both human serum-resistant and sensitive strain of T.b. rhodesiense, and from the bodonid member of the Kinetoplastida Trypanoplasma borelli. (4) Several control experiments including 35S-metabolic labeling of procyclic T.b. brucei and of C. luciliae followed by LDL-affinity chromatography or immunoprecipitation demonstrate that gp145 is indeed synthesised by the parasites and is not a contaminant of the experimental system. (5) In immunoblots and ELISA, these gp145 cross-react with the polyclonal and monoclonal antibodies raised against the LDL-receptor of T.b. brucei, the highest degree of cross-reactivity being found among the members of the Trypanozoon subgroup. (6) Finally, immunisation of mice with the purified LDL-receptor from one strain of T.b. brucei is not sufficient to confer durable protection against another strain of this parasite.

Animals↗

Epitope-specific down-regulation of anti-allergen antibodies following injection of allergen-antibody complexes in hypersensitive patients.

Administration to allergic patients of complexes made of allergen and anti-allergen antibodies results in a reduction in the levels of specific IgE and IgG antibodies that is limited to antibodies present in the complexes. The epitope-specific nature of this reduction is demonstrated by taking advantage of the cross-reactivity between Der p I and Der f I. In addition, an increased production of anti-idiotypic antibodies is demonstrated. As such treatment significantly improves patients with allergic asthma or atopic dermatitis, it may represent a valuable alternative to conventional immunotherapy.

Adult↗