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Biomedical subjects

A Durandy

Publications and source records attributed to A Durandy.

At least 55 records · Page 3Linked to original sources
PubMed1993

Prenatal diagnosis of syndromes associating albinism and immune deficiencies (Chediak-Higashi syndrome and variant).

We have successfully undertaken the prenatal diagnosis of two hereditary syndromes associating albinism and immune defects. Because the genes responsible for these diseases have not yet been mapped and the immune abnormalities are too subtle to be diagnosed in utero, the prenatal diagnosis was made using a morphological approach. In the case of Chediak-Higashi syndrome, it was based on light microscopic examination of the hair shaft and on light and electron microscopic study of polymorphonuclear cells. In the syndrome associating immune deficiency and partial albinism, the Griscelli syndrome, only examination of the hair was feasible. The diagnosis was negative in 12 fetuses at risk and positive in four.

Albinism↗
PubMed1993

Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients.

We carried out a retrospective analysis of 117 patients with severe combined immunodeficiency who were examined in a single center between Jan. 1, 1970, and Jan. 1, 1992, for the purpose of evaluating disease onset, progression, and outcome. The frequency of case referral increased from 8 from 1970 to 1975 to 56 from 1986 to 1991. The most frequent phenotype was T-/B+ (absence of T lymphocytes and presence of B lymphocytes) (n = 51); there were 36 cases of alymphocytosis, 16 of adenosine deaminase deficiency, 13 of Omenn syndrome, and 1 of reticular dysgenesis. Protracted diarrhea and lung infections were the main infectious complications; infection with bacillus Calmette-Guérin occurred in 10 of 28 vaccinated patients, but none of the six recipients of oral polio vaccine subsequently had poliomyelitis. The presence of maternal T cells was suspected or proved in half the patients with alymphocytosis or T-B+ severe combined immunodeficiency but did not occur in the other forms of the disease. Of the 117 patients, 22 died before transplantation could be performed. Adenosine deaminase deficiency and Omenn syndrome were more frequently associated with death before hematopoietic stem cell transplantation was possible. Fetal liver transplantation was successful in 1 of 10 cases. The survival rate among the 30 recipients of bone marrow with identical human leukocyte antigens (HLA) was 80%, with a median follow-up of 129 months; 23 of 25 patients recovered full immune function. The survival rate among the 50 recipients of HLA-haploidentical T cell-depleted bone marrow was 56%, with a mean follow-up of 35 months. Of the latter patients, 10 (35%) still require immunoglobulin substitution. There has been a trend toward improvement in the survival rate of haploidentical bone marrow recipients, presumably because of more effective infection-control measures and better transplantation strategy.

Bone Marrow Transplantation↗
PubMed1993

Therapy for transplant-related lymphoproliferative diseases.

Epstein-Barr virus can induce an uncontrolled B cell proliferation called B lymphocyte proliferative disorder (BLPD) in immunocompromised hosts. It is a complication that is increasing in prevalence with the growing frequency of transplantation. About 40% of BLPD are reversible following reduction of immunosuppressive therapy. In other instances, BLPD are often fatal with the exception of localized tumors that can be surgically excised. Therapeutic strategies have included antiviral drugs, alpha-interferon, and anti-B cell antibodies.

Animals↗
PubMed1992

Carrier detection and prenatal diagnosis of X-linked agammaglobulinemia.

We investigated the pregnant mother of a boy with X-linked agammaglobulinemia (XLA) but with no family history of immune disease. The X-inactivation pattern was found, using a methylation-sensitive probe, to be skewed in the maternal B cells but random in the polymorphonuclear cells, indicating carrier status and a 50% risk of inheritance for her male fetus. Using probes assigned to regions on either side of the XLA locus and defining RFL polymorphism, we excluded for the first time a diagnosis of XLA on a chorionic villus sample, with a risk of error less than 0.003. Immunological studies performed at the 19th week of gestation and 3 days after birth confirmed normality. Carrier detection based on the X-chromosome inactivation pattern, together with prenatal studies using probes close to the disease locus, thus permits prenatal diagnosis in families with isolated cases of XLA.

Agammaglobulinemia↗
PubMed1992

Spontaneous IgM autoantibody production in vitro by B lymphocytes of normal human neonates.

Human neonate B lymphocytes display unique phenotypic and functional characteristics: in addition to CD1c antigens, CD5+ and CD5- subsets both express activation markers such as CD23 and Bac-1. They proliferate strongly in the presence of various lymphokines (rIL-2, rIL-4, low molecular weight BCGF), but differentiate poorly in the presence of the same lymphokines, pokeweed mitogen and Epstein-Barr virus. It has also been reported that human neonate B lymphocytes produce polyreactive autoantibodies after in vitro activation by Staphylococcus aureus Cowan I and transformation by Epstein-Barr virus. We now show that, in the absence of in vitro stimulation, human neonate B lymphocytes produce polyreactive antibodies of the IgM isotype against several autoantigens. The B lymphocytes involved expressed membrane IgD, IgM, CD23 and CD11b molecules; CD5 expression was variable. This phenotype was consistently found on a minority of B lymphocytes and is similar to that of polyreactive autoantibody-producing B cells in mice. We also found that autoantibody production in vitro could occur in the absence of any T helper effect. The function of these autoantibodies is not clearly established, but their occurrence in a large proportion of human neonates strongly suggests that they play an important role in the development of the immune system.

Adult↗
PubMed1992

Control of human B cell tumor growth in severe combined immunodeficiency mice by monoclonal anti-B cell antibodies.

Severe combined immunodeficiency (scid) mice develop EBV (+)B cell tumors after infusion of EBV(+)B cells or of B cells and EBV. In this study, scid mice were infused with B cell lines derived from three patients who developed a B lymphocyte proliferative disorder after bone marrow or organ transplantation. Intraperitoneal injection of 5 x 10(6) B cells induced tumor growth in all mice, leading to death within 60 d. Human B cells were identified in spleen and bone marrow by means of immunofluorescence or EBV genome amplification, and human IgM was detected in serum. Infusion of murine monoclonal antibodies specific for human B cell membrane antigens CD21, CD24, and CD23 was effective in 80% of animals, against two of the three cell lines preventing tumor development or inducing remission according to the time of treatment. The effect was antibody dose dependent and was optimal with four intravenous infusions of at least 0.1 mg 4 d apart. Human IgM in serum and human B cells in spleen and bone marrow became undetectable when peritoneal tumors regressed completely. Infusions of IgG1 isotype-matched anti-CD4 antibody or anti-CD3 antibody had no effect. Tumors developed or recurred in 50% of these animals injected with one of the B cell line 3 mo after treatment was stopped. The same anti-CD21 and anti-CD24 antibodies had been used to treat the three patients, and shown similar degrees of effectiveness as in the scid mouse model. These results indicate that scid mice may be suitable for assessing therapeutic approaches to human B cell proliferation.

Animals↗
PubMed1992

[Development of the immune system].

The development of immune defense mechanisms begins early during fetal life but is not yet completed at birth. The earliest hematopoietic stem cells, which give rise to the lymphocytic and myelomonocytic cell lines, appear between the fourth and eight weeks postconception. T cells, responsible for cellular immune defense mechanisms, are first detectable at 12 weeks and seem to acquire their functional capabilities at the 16th week. B lymphocytes, responsible for humoral immunity, can be identified in the fetal liver at eight weeks and are functional at the 12-th-13th week, with the ability to produce specific IgM antibodies. Thus, in theory, fetuses of more than 16 weeks can produce a full immune response. Neonates still have incomplete development of a number of mechanisms involved in nonspecific immunity (natural killer, polynuclear and macrophage chemo-attraction, complement system).

B-Lymphocytes↗
PubMed1992

Hematopoiesis in the human yolk sac: quantitation of erythroid and granulopoietic progenitors between 3.5 and 8 weeks of development.

In a first attempt to investigate the regulation of the early steps of human embryonic hematopoiesis, we measured the number of erythroid and granulopoietic progenitors in 38 human yolk sacs and 15 embryonic livers between 27 and 62 days of development. Both erythroid and granulopoietic progenitors were identified in the yolk sac as soon as 27 days, while in the embryonic liver significant numbers were not observed before 40 days. In the yolk sac, the number of granulopoietic and/or macrophagic progenitors was significantly negatively correlated with gestational age. Such a correlation was not observed for CFU-E and BFU-E, even though in the youngest (less than 30 days) and the oldest embryos studied (greater than 40 days), the number of BFU-E was clearly lower.

Cell Count↗
PubMed1991

Anti-CD3 antibody-induced lymphocyte proliferation: a new tool for the prenatal diagnosis of some inherited immune deficiencies.

We have compared anti-CD3 monoclonal antibody-induced proliferation of T lymphocytes from normal human fetuses and neonates with that of adult T cells. In contrast to data in the literature, we consistently observed a strong proliferative response during antenatal and perinatal life. A lack of anti-CD3-induced proliferation, despite normal responses to the mitogen phytohemaglutinin, may prove to be a useful criterion in the diagnosis of some ill-defined inherited immune deficiencies.

Adult↗
PubMed1990

Phenotypic and functional characteristics of human newborns' B lymphocytes.

It has been demonstrated two major facts concerning human newborns' B lymphocytes: 1) they differentiate poorly into Ig-producing cells and 2) they express CD5 and CD1c membrane proteins. We have further analyzed human newborns' B cell characteristics and found that approximately half of them express activation Ag, i.e., 4F2 and IL-2R, both associated in significant proportions with CD23 and Bac-1. These membrane Ag were found both on CD5(+) and CD5(-) B cells. Newborns' B cells do not exhibit other activation markers because they express surface IgD, and because their size, RNA, and DNA contents do not differ from those of adults' B cells, indicating that they are in the G0/G1 cell cycle phase. Newborns' B cell proliferation can be induced by rIL-2, rIL-4, low m.w. B cell growth factor, and by Staphylococcus aureus protein A. It is presently difficult to build a hypothesis accounting for all the specific findings made on newborns' B cells. It is not known for instance whether CD5(+) and (-) B cells belong to distinct subsets as suggested by the fluorescence intensity curve obtained with an anti-CD5 antibody or to distinct stages in a unique pattern of B cell maturation during fetal and newborn life. This may indicate that partially activated B cells actually produce natural polyspecific autoantibodies of the IgM isotype found in newborns' human serum.

Antigens, CD↗
PubMed1990

Selective IgG subclass deficiencies and antibody responses to pneumococcal capsular polysaccharide antigen in adult community-acquired pneumonia.

We measured the serum concentrations of IgG subclasses in healthy subjects (n = 26) and in patients with community-acquired pneumonia (CAP) on admission (n = 38), at recovery (n = 21), and 9 months after admission (n = 19). Then, in 8 of the control subjects and 15 of the patients, we measured IgG subclasses and mean serum antibody concentrations of pneumococcal capsular polysaccharides before and 3 wk after immunization with a pneumococcal vaccine. Compared to the control subjects, the serum concentration of the IgG2 subclass was lower at admission in patients with CAP of bacterial or unknown cause (p less than 0.005). Concentrations of IgG subclasses in patients did not differ between admission and recovery, or between admission and 9 months later. After vaccination, in both control subjects and patients, there was an increase in the concentrations of IgG2 subclasses (p = 0.01) and antipneumococcal antibodies (p less than 10(-4)). We show that serum IgG2 concentration in patients with CAP of bacterial or unknown cause is lower than in healthy subjects and remains lower for several months. After immunization with a pneumococcal vaccine, the increase in serum concentrations of IgG subclasses and antipneumococcal antibodies in patients does not differ from those in control subjects.

Aged↗
PubMed1989

Activation of genetically major histocompatibility complex (MHC) class II-deficient B lymphocytes.

It has been suggested that MHC class II molecules can transduce signals required for B-cell activation. Enhancement or inhibition of B-cell stimulation by anti-MHC class II molecule antibodies has likewise been reported. The study of B cells from patients with a combined immune deficiency due to a defective expression of MHC class II genes provides a useful tool for approaching the functional role of B-cell HLA class II molecules. We have thus analyzed the specific and nonspecific, cognate and noncognate B-cell activation of genetically HLA class II-deficient lymphocytes. B lymphocytes from 14 tested patients were able to synthesize RNA following stimulation with ionomycin and phorbol myristate acetate or anti-mu antibodies and with mannan, a T cell-independent polysaccharidic antigen. They were also able to synthetize DNA following the addition of ionomycin and PMA or of anti-mu antibodies in the presence of recombinant interleukin 2. Pokeweed mitogen failed to induce B-lymphocyte terminal differentiation into immunoglobulin-producing cells in the presence of normal T lymphocytes, while a combination of anti-CD2 antibodies were capable of triggering IgG synthesis. B-cell activation, whatever the condition used, did not induce HLA class II expression. Mannan-specific T cell-dependent antibody production (IgM) was detected in 6 of 14 patients. Anti-influenza virus antibody production was always found absent. These results are compatible with the hypothesis that B-cell activation events that do not require a cognate interaction with T cells can occur in the absence of HLA class II molecule expression, while the absence of HLA class II molecule expression prevents T-B cognate interaction.

Adolescent↗
PubMed1989

Direct activation of human B lymphocytes by Candida albicans-derived mannan antigen.

We have studied the activation of human resting B cells by a carbohydrate antigen, mannan, with a polymannose branched repetitive structure. Mannan has been extracted from the cell wall of the Candida albicans yeast. For this purpose, dense G0 B lymphocytes were purified from tonsils. Mannan antigen was shown to trigger B cell activation, since an increase of cell volume and RNA synthesis occurred. B cell proliferation was observed following addition of recombinant interleukin 2, but not following addition of recombinant interleukin 4 or low-molecular-weight BCGF. The B cell activation appears to be mannan-specific since B cells obtained from mannan-sensitized subjects but not from unsensitized subjects were responsive. The observation that mannan antigen can directly activate specific dense B lymphocytes can be related to the previous observation that the in vitro anti-mannan antibody production does not require a cognate T-B cell interaction.

Antigens, Fungal↗
PubMed1989

Combined immunodeficiency with abnormal expression of MHC class II genes.

The MHC class II CID represents an example of immunodeficiency in which the defect in expression of membrane glycoproteins leads to abnormal cell to cell interactions and thus to abnormal immune responses. It represents an interesting model which confirms the importance of MHC molecules in all immune responses to foreign antigens. It also underlines the complexity of regulatory mechanism which control the expression of MHC class II genes. To elucidate these mechanisms, it is essential to identify and characterize the genes involved in control of MHC class II expression.

Agammaglobulinemia↗
PubMed1989

[Prenatal diagnosis of severe and hereditary immune deficiencies].

Antenatal diagnosis is now available for most severe inherited immune deficiencies. Several techniques are used: the development of methods for sampling fetal tissue as soon as the tenth week of gestation has made possible the antenatal diagnosis of immune deficiencies associated with detectable enzyme defects, and, in combination with recent molecular biology techniques, can be expected to allow early identification of severe combined immune deficiencies due to the absence of T lymphocyte precursors, agammaglobulinemia, and some instances of X-linked chronic granulomatous disease. A great number of immune deficiencies can be identified by direct studies of fetal lymphocytes or polymorphonuclear leukocytes in fetal blood sampled by fetoscopy at the twentieth week of gestation. Fetal blood studies combined with skin biopsy examination allows the diagnosis of immune defects associated with partial albinism such as Chediak-Higashi disease. No reliable antenatal diagnostic method is as yet available for two severe diseases: Wiskott-Aldrich syndrome, that can be expected to become detectable in utero using molecular biology techniques, and ataxia-telangiectasia. Antenatal diagnosis of a severe immune deficiency does not necessarily indicate termination of the pregnancy as in some cases, such as severe combined immune deficiencies, HLA-identical bone marrow transplantation at birth or in utero is permanently successful in over 90% of cases.

Female↗