Anaphylactic reaction to intravenous cyclosporine.
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Adult↗
Biomedical subjects
M Jeannet
Publications and source records attributed to M Jeannet.
Mating is random.
Human leukocyte antigen (HLA) typing was undertaken in 151 unrelated blood donors and in 35 normal couples having at least two living children. We compared observed and expected sharing of HLA antigens at four loci in normal couples. We also compared the observed sharing in couples with the expected sharing in unrelated blood donors if taken two by two and with the sharing observed after 1000 "synthetic matings" of normal couples. No statistically significant difference in HLA sharing appeared between these groups. Furthermore no differences were observed in the probabilities of sharing individual HLA antigens among the different groups. We thus conclude that the observed HLA sharing in normal couples is governed by chance alone and that mating is random in our population.
Female↗
[Acquired immunodeficiency syndrome, chronic coccidiosis and Salmonella typhimurium septicemia in a couple from Zaire. Immunological functions and attempt at immunostimulation by thymopentin].
A clinical review of a young couple from Zaïre with acquired immunodeficiency syndrome (AIDS) is reported. Both had opportunistic infections such as Salmonella typhimurium septicemia, genital herpes and digestive candidiasis. The husband was hospitalized for diarrhea from Isospora belli infection and for hemoptysis from an aspergilloma. His wife was admitted for a thoracic herpes zoster infection and left hemiplegia preceding subacute encephalitis. In both patients the biological immune functions were compatible with AIDS: presence of antibody against lymphadenopathy virus, decreased in OKT4+/OKT8+ ratio, and lack of lymphocyte response to mitogens which was partially restored in vitro after addition of interleukin 2 and thymopentin (TP-5) in the husband. In vitro monocyte cultures showed increased production of prostaglandins E2 (PGE2) and a slight decrease in interleukin 1 production. The symptomatic treatments and an attempt at immunostimulation with TP-5 in the husband are described.
Acquired Immunodeficiency Syndrome↗
[Current status of allogenic bone marrow transplantation in chronic myelocytic leukemia].
Bone marrow transplants were carried out in 18 patients with chronic myelogenous leukemia (CML) in the chronic phase (CP). 12 (67%) are still alive, 11 without evidence of leukemia after a mean observation period of 24 (3-44) months, 1 relapsed and 6 died. The most frequent cause of death was GvHD and interstitial pneumonia (5). 1 patient died of septicemia. 2 grafts were performed in patients with CML in the accelerated phase (AP); both died, one from leukemic relapse and one from GvHD. The authors also participated in an international study in which 117 patients were evaluated. In CP there was a survival plateau at 63%, in AP at 36% and in blastic crisis at 12%. In CP mortality was primarily age-dependent and relapses occurred in only 7%. It is concluded that bone marrow transplantation (BMT) is a highly successful treatment for CML, with the CP the optimum moment for grafting. Longlasting cytogenetic and clinical remissions with potential for cure are possible in a high percentage of patients. The incidence of transplant-related mortality is acceptable. The incidence of leukemic relapse is low in CP. Patients under age 40 with HLA-identical siblings should be transplanted in CP. At present BMT is the only treatment with curative potential for CML.
Adolescent↗
HLA-DR antigens and the antibody response against Epstein-Barr virus.
Antibodies against Epstein-Barr virus (EBV) antigens, i.e. the viral capsid antigen (VCA) and the Epstein-Barr nuclear antigen (EBNA), were determined in two independent populations with known HLA-DR phenotypes. The first population consisted of 151 patients with rheumatoid arthritis; the second one of 88 healthy parents of leukemic children. Although the group of patients with rheumatoid arthritis differed significantly in the frequency of 4 DR antigens from the second group, both groups had the same correlation between HLA-DR antigens and the antibody response to EBV antigens. There was a significant correlation between HLA-DR1 and reduced titers of antibodies to VCA, whereas the persons with only one identifiable DR antigen had higher anti-VCA titers. The persons with HLA-DR5 had significantly higher anti-EBNA titers than those without DR5.
Adult↗
Circulating immune complexes in regularly dialyzed patients with chronic renal failure.
The prevalence of circulating immune complexes (CIC) was investigated using the C1q binding assay (C1q BA) and the conglutinin binding assay (Kg BA) in 200 patients undergoing maintenance hemodialysis. Increased C1q binding was found in 45% (87 of 194) of the patients, and the modified Kg BA gave elevated values in 31% (20 of 65). The prevalence of CIC was similar in American and Swiss patients, and in patients undergoing hemodialysis, self-dialysis or peritoneal dialysis. In patients with 'nonimmunological' renal diseases, CIC were detected with similar frequency. No change in CIC was noted during hemodialysis in 6 additional patients tested. The abnormality was not related to age, sex, duration of dialysis, hepatitis B antigenemia, bacterial infections, or transfusions. Anti-DNA antibodies were absent in all subjects tested and the results of the C1q BA were not changed by DNase digestion of eight sera with high C1q binding. Rheumatoid factor activity (RF) was detected in approximately one-fifth of the patients, and there was a direct correlation between positive C1q binding and RF. There was no correlation between CIC and lymphocytotoxic antibodies. This study demonstrated a high prevalence of CIC in dialyzed uremic patients and established its relationship to other immunological abnormalities.
Antibodies, Antinuclear↗
Circulating beta-2-microglobulin levels during pregnancy and their possible relationship with feto-maternal histocompatibility.
Plasma beta 2 microglobulin (beta 2m) levels have been measured by radioimmunoassay in normal pregnant women, in two successive pregnancies of a woman who shares HLA antigens with her husband, in normal twin pregnancies, in toxemic pregnancies and in hydatidiform moles. During normal pregnancy, plasma beta 2m levels decrease reaching a minimum at week 14 and increase thereafter to a maximum at week 34. In the two successive pregnancies of the one patient with HLA compatibility, beta 2m concentrations were significantly lower than in normal pregnancies. Women with monozygotic twins had significantly less beta 2m than women with heterozygotic twins. Toxemic patients bearing female fetuses had also statistically lower beta 2m levels than toxemic women with male fetuses. Patients suffering from hydatidiform moles had beta 2m levels in the range of normal pregnant patients. Since circulating beta 2m is produced by lymphocytes one might assume that low beta 2m levels reflect a reduced activity of lymphocytes. The results presented here allow to propose a hypothesis which will have to be verified that reduced beta 2m levels are associated with an increased feto-maternal histocompatibility.
Adult↗
[From anguish to aggression: an experience in an intensive care unit].
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Aggression↗
Treatment of severe aplastic anemia: a prospective study of antilymphocyte globulin versus bone marrow transplantation.
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Adolescent↗
[Bone marrow transplantation in acute lymphatic leukemia during the first remission].
9 patients with acute lymphoblastic leukaemia (ALL) were transplanted in first remission. There were no leukaemic relapses and 6 patients became longterm survivors. Causes of death were GvHD in 2 and interstitial pneumonia in 1. 14 patients with ALL were grafted in later stages of the disease. 10 had a leukaemic relapse. One attained longlasting remission with chemotherapy, while 9 died. One patient died of CMV infection. Cotton wool lesions and haemorrhages in the retina posed a problem in patients with previous cranial irradiation. We recommend transplantation of ALL in first remission if a syngeneic or HLA-identical sibling is available, particularly if the patient has poor risk factors for chemotherapy. Prophylactic cranial irradiation should be replaced by intrathecal methotrexate and/or cytosin arabinoside in these patients.
Adolescent↗
[Genetic factors linked to the HLA system conferring increased susceptibility to acute lymphoblastic leukemia in children].
Inheritance of HLA antigens in 55 families of patients with ALL was analyzed. Significantly increased sharing of DR antigens was observed among the parents of the affected children (p = 0.003). A similar increase was noted in the sharing of HLA-B antigens (p = 0.02). The observed number of DR homozygotes among the patients was twice the expected value in families where the parents shared a B and a DR antigen. Segregation analysis of the shared antigens disclosed significant prevalence of heterozygotes among the healthy siblings, which suggested the occurrence of gametic selection in such families. This study indicates that mating of certain shared alleles of the HLA system (especially of the DR locus) is associated with a risk for the offspring to develop ALL in childhood. Restricted heterogeneity of the parental HLA gene pool favours the expression of linked recessive genes and, presumably, of those involved in susceptibility to ALL.
Child↗
[Bone marrow transplantation in leukemia and aplastic anemia].
In a review of allogeneic bone marrow transplantation (BMT) for leukemia the following points proved to be of crucial importance: (1) combination of cyclophosphamide (Cy) and total body irradiation (TBI) for conditioning, (2) early BMT for acute leukemia (AL) in first remission and for chronic granulocytic leukemia (CGL) in chronic phase, (3) prophylaxis of graft-versus-host disease (GvHD) with cyclosporin-A (CyA). 50 successive BMT for leukemia performed in Basel between July 1979 and September 1982 are analyzed. 7 of 13 acute myelogenous leukemias (AML) and 8 of 9 acute lymphatic leukemias (ALL) grafted in first remission, and 7 of 10 CGL, are alive without signs of leukemia and without chronic problems. Of the patients grafted for AL in second remission or later, 3 of 6 AML and 6 of 12 ALL are alive. Severe GvHD was seen in 5 of 43 BMT between HLD identical siblings, in three of them combined with interstitial pneumonia. Thus the incidence of these two serious complications of allogeneic BMT has been drastically reduced with CyA compared to our previous experience with prophylactic methotrexate (MTX). 4 grafts were performed between HLA-haploidentical siblings. 3 of the 4 patients developed fatal GvHD. This implies that in this histocompatibility setting CyA alone is not sufficient. No problems were encountered in 3 syngeneic BMT. 12 leukemic relapses were observed. Relapse never occurred in ALL in first remission and never in CGL. 4 recurrences were seen in AML in first remission. All other relapses were in patients with AL grafted in stages other than first remission. In 86 successive patients with severe aplastic anemia (SAA) the following important advances were made: (1) it was shown that the majority of patients have sufficient hemopoietic stem cells and that after treatment with antilymphocyte globulin (ALG) over 70% have long-lasting remissions, (2) the combined treatment with ALG and high dose prednisone increases the remission rates to 90% and in addition shortens the supportive care period significantly. These developments are of crucial importance for patients without an HLA-identical sibling, (3) success rates of marrow transplants between HLA-identical siblings could be increased from 36% with prophylactic MTX to 67% using CyA.
Anemia, Aplastic↗
Evidence for HLA-linked susceptibility factors in childhood leukemia.
To test the hypothesis that susceptibility to leukemia can be governed by (a) recessive gene(s) associated with the major histocompatibility complex (MHC) in man, we performed an analysis of the inheritance of HLA antigens in 55 families in which one of the children developed ALL. We found among the parents of affected children a highly significant increased compatibility at the DR locus (p = 0.003). A similar increase was observed in sharing HLA antigens of the B locus (p = 0.02). The observed number of homozygotes among the patients was twice the expected value in families where the parents shared a B and a DR antigen. In segregation analysis, heterozygotes for the shared parental HLA antigen were significantly more prevalent among the healthy siblings. Our genetical analysis indicates that mating of certain shared alleles of the HLA system (especially of the DR locus) is associated with the risk for the offspring to develop ALL in childhood. This situation favors the expression of recessive genes associated with the MHC, and presumably those involved in the susceptibility to acute leukemia. Because familial leukemia is a rare event, the susceptibility to childhood ALL must also implicate genes outside the MHC and important environmental factors.
Child↗
Immunologic reactivity in marrow graft recipients receiving cyclosporine to prevent graft-versus-host disease.
In vitro and in vivo immunologic parameters were determined in 26 patients treated continuously with cyclosporine to prevent graft-versus-host-disease (GVHD) after allogeneic bone marrow transplantation (BMT) for acute and chronic leukemia and for aplastic anemia. A group of 18 patients was tested 6 months after BMT and another group of 10 patients was tested after one year. At 6 months after BMT, 94% of the patients had normal serum IgG and IgM levels, whereas at one year 29% of them had low IgA levels. The proportion of patients with normal lymphocyte responses in vitro at 6 months after BMT was 69% and 76% for the responses to concanavalin A and to soluble antigens; 75% and 53% for the responses to allogeneic cells and pokeweed mitogen, respectively; and 89% for the response to phytohemagglutinin. All but one were able to generate suppressor cells upon con A stimulation. At one year after the graft, only one patient had demonstrable multiple abnormalities in in vitro tests. Skin test reactivity at one year was comparable to pre-graft reactivity. After BMT a lymphopenia persisted for 6 months. The rate of infectious complications was high during the first 3 months after BMT, and it diminished progressively as immune functions returned to normal. Infection was the cause of death in two cases (one disseminated cytomegalovirus infection and one septicemia). GHVD occurred in 12 patients; in nine of them the disease was transient and mild, only 1 patient developed severe chronic GVHD. Acute GVHD did not influence the tempo of immunologic reconstitution. In comparison to other studies, it seems that cyclosporine does not delay immune restoration, or increase morbidity from infection, while preventing GVHD and its complications efficiently.
Anemia, Aplastic↗
Human T cell clones allospecific for HLA-DR5 antigen with the OKT8 phenotype.
Human allospecific T-lymphocyte clones reactive in the primed lymphocyte (PLT) and/or the CML assays were established and grown using T cell growth factor and weekly stimulation with a pool of allogeneic feeder cells. Specificity of selected clones was determined by their reactivity with a panel of HLA-typed lymphocytes. The phenotype of the clones was identified by monoclonal antibodies and complement lysis. Two weakly cytolytic clones, which specifically proliferated in response to DR5 bearing lymphocytes in PLT, possessed the OKT8 marker, suggesting that this determinant is not exclusively involved in the recognition of class I antigens.
Antibodies, Monoclonal↗
A reevaluation of the concanavalin A induced suppressor cell assay in man.
Several methods are used to evaluate the in vitro suppressor function of human peripheral blood lymphocytes (PBL). Recently however, the validity of these assays has been questioned, because possible artefacts may lead to misinterpretation of the results. A reevaluation of these assays has been performed, and a simple and reproducible technique necessitating only one bleeding has been developed. Pretreatment of human PBL with concanavalin A (ConA) results in an inhibition of 3H-thymidine incorporation after ConA stimulation by cocultured untreated autologous or allogeneic PBL collected at the same time and incubated under the same conditions as the inhibitory PBL. It is concluded that true suppression is responsible for the observed inhibition of the response to ConA and that this assay can be used to assess the functional ability of suppressor cells in different clinical situations.
Concanavalin A↗
Bone marrow graft versus ALG in patients with aplastic anaemia.
Eighty-six successive patients with severe aplastic anaemia were admitted to this hospital between January 1976 and October 1982. They were treated and evaluated in a prospective study according to one protocol. 26 patients with an HLA identical sibling underwent bone marrow transplantation. Overall survival calculated according to Kaplan and Meier in this group is 47%, 60 patients without an HLA identical sibling were given antilymphocyte globulin with or without an infusion of HLA-haploidentical marrow. All these 60 patients received low dose androgens after the procedure. In this study the marrow infusion did not significantly improve the results and overall survival was 74% compared to 70% in patients receiving only antilymphocyte globulin and androgens. In a current pilot study combining ALG and high dose prednisone we were able to further increase remission rates. Between HLA-identical siblings we improved the results of marrow transplants significantly by the use of cyclosporin-A instead of methotrexate for prophylaxis against GvHD.
Adolescent↗
Corticoresistant nephrotic syndrome associated with T-cell deficiency in two sisters.
The coexistence in two sisters, born to related parents, of a corticoresistant nephrotic syndrome, lymphopenia, an immune deficit, short stature, and photophobia is described. The immune deficit is mainly cellular; studies of lymphocyte markers demonstrate a pronounced deficiency of T lymphocytes and Fc-mu receptor-bearing cells. It is suggested that a thorough examination of number and function of T cells should be performed in patients with a familial corticoresistant nephrotic syndrome and recurrent infectious episodes before considering immunosuppressive treatment.
Child↗