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Biomedical subjects

F H Claas

Publications and source records attributed to F H Claas.

At least 199 records · Page 11Linked to original sources

Induction of B cell unresponsiveness to noninherited maternal HLA antigens during fetal life.

Patients who have received many transfusions become highly sensitized and develop antibodies against almost all HLA alloantigens, so that finding a cross-match negative kidney donor is difficult. A survey of those patients showed that 50 percent did not form antibodies against the noninherited maternal HLA antigens. Apart from the obvious clinical implications, the data indicate that a human equivalent of murine neonatal or actively acquired tolerance has now been identified.

B-Lymphocytes↗

The hyperimmunized patient: from sensitization toward transplantation.

Hyperimmunized patients tend to accumulate on renal transplant waiting lists because their high level of sensitization leads to positive crossmatches with almost all potential organ donors. The origins of sensitization and the different efforts made to find crossmatch-negative donors for these patients are discussed. Special emphasis is given to a local strategy based on the determination of HLA-A and -B mismatches, against which the patient did not form alloantibodies, the so-called acceptable mismatches. Kidney donor selection is based on compatibility with the patients' own HLA antigens in combination with the acceptable HLA-A and -B antigens and can be operated from a central organ-sharing office.

HLA-A Antigens↗

Genetics of two human monocyte antigens.

HMA-1 and HMA-2 are two serologically defined alloantigens that are present on human monocytes and granulocytes. Previous panel studies suggested that these two antigens comprise a diallelic system. We therefore performed segregation studies on 10 randomly chosen families and on 22 nucleus families belonging to one large pedigree. All individuals were either positive for HMA-1, HMA-2, or both. Segregation of HMA-1 showed autosomal inheritance with complete penetrance. The cytotoxicity negative, absorption positive (CYNAP) phenomenon sometimes occurred for HMA-2, and because absorptions for HMA-2 could not be performed on all cells, linkage studies were only performed for HMA-1. No linkage of HMA-1 with HLA, immunoglobulin allotypes, granulocyte antigens, or any of the erythrocyte blood groups tested was observed.

Alleles↗

Differential immune response of congenic mice to ultraviolet-treated major histocompatibility complex class II-incompatible skin grafts.

The influence of ultraviolet (UVB) irradiation on the survival of H-2 class II-disparate skin grafts was studied in congenic mouse strains. Isolated skin was UVB irradiated in vitro at a dose of 40 mJ/cm2 from both sides to remove Ia immunogenicity. Immediately after irradiation the skin was transplanted onto the flank of allogeneic mice. When B10.AQR grafts were transplanted onto B10.T(6R) recipients, a significant prolongation of the survival time was observed, while 50% of the UVB-treated grafts were not rejected at all. However, in the opposite direction--i.e., B10.T(6R) grafts onto B10.AQR recipients, no significant prolongation of the survival was observed. To test whether this effect was due to a difference in susceptibility of the donor skin to UVB irradiation or to a different immune response in the recipients, (B10.T(6R) x B10.AQR) grafts were transplanted onto the parent strains. Similar results were obtained, in that UVB-treated grafts did not show a prolonged survival in B10.AQR recipients, whereas a significant prolongation (50% of the grafts survived more than 100 days) was observed in B10.T(6R) recipients. UVB-treated (B10.T(6R) x B10.AQR)F1 grafts were also transplanted onto (B10.T(6R) x C57B1/10)F1, (B10.AQR x C57B1/10)F1, (B10.T(6R) x Balb/c)F1 and (B10.AQR x Balb/c)F1 recipients--but in none of these combinations was a prolonged survival time observed. These data suggest that, in contrast to all in vitro experiments, the abrogation of the immune response by UVB treatment of the stimulator cells is, in vivo, not a general phenomenon. The genetic constitution of the responder mice seems to play an important role in determining whether or not an immune response takes place.

Animals↗

Beneficial effect of intravenous gammaglobulin in a patient with complement-mediated autoimmune thrombocytopenia due to IgM-anti-platelet antibodies.

Intravenous gammaglobulin (IV-IgG) was administered to a patient with chronic idiopathic thrombocytopenic purpura due to an unusual IgM platelet autoantibody causing in vitro complement-dependent thrombocytoxicity and in vivo intravascular platelet destruction. After IV-IgG infusion the peripheral platelet count temporarily increased to normal values, the mean platelet survival time increased and the platelet sequestration pattern changed from intravascular to predominantly hepatic destruction. In vivo and in vitro observations in this patient illustrate a transient beneficial effect of gammaglobulin infusion due to interference with the complement-fixing autoantibodies against platelets.

Aged↗

9a: risk factor in bone marrow transplantation?

Graft-versus-host disease is a severe complication which may occur even after bone marrow transplantation between HLA identical siblings. Minor transplantation antigens have been implicated as a causal factor. Therefore the influence of the monocyte/granulocyte antigen 9a on GvHD was studied. No influence on GvHD was observed, but absence of the 9a antigen in the donor was associated with an early death of the recipient.

Bone Marrow Transplantation↗

Alloimmunization after leukocyte-depleted multiple random donor platelet transfusions.

In a prospective study we investigated the development and the course of alloimmunization after leukocyte-depleted red cell and multiple random donor platelet transfusions in 335 patients. Of these 335 patients, who had a negative antibody screening on admission and a negative transfusion history, 69 (21%) developed either transient (n = 18) or permanent (n = 51) lymphocytotoxic antibodies, but only 31 patients (9%; 95% confidence limits 6-12%) developed multispecific alloantibodies necessitating HLA-matched platelet transfusions. There was no difference with regard to the development of antibodies and platelet refractoriness between leukemia patients receiving cytostatic treatment and patients with aplastic anemia receiving prednisone and antithymocyte globulin. Females with previous pregnancies developed platelet refractoriness with an increased incidence (Chi 2 13.38; p less than 0.001) compared to females without previous pregnancies, males, and children.

Blood Platelets↗

Two alloantigens on human monocytes: a diallelic system?

A positive monocyte crossmatch and therefore anti-monocyte antibodies are negative factors in bone marrow and renal transplantation. When the monocyte antigens themselves can be recognized, matching for the antigens involved here may become a possibility. In order to find useful anti-monocyte sera as typing reagents, human sera were screened against panel cells. Several monocyte specific sera were obtained. These sera recognized two monocyte antigens, HMA-1 and HMA-2. No similarity with any of the HLA antigens was observed. Every individual tested was positive for at least one of these two monocyte antigens, suggesting that HMA-1 and HMA-2 constitute a diallelic system.

Fluorescent Antibody Technique↗

Correspondence of the monocyte antigen HMA-1 to the non-HLA antigen 9a.

Monocyte-specific antibodies are detrimental to bone marrow and renal transplantation. By using human antimonocyte sera we were able to identify two monocyte-specific antigens, human monocyte antigen 1 and 2 (HMA-1 and HMA-2). The presence of HMA-1 and HMA-2 was compared with the presence of several non-HLA antigens. In panel and inhibition studies, HMA-1 corresponded to the previously described non-HLA granulocyte antigen 9a. Absorption studies showed that HMA-1 and 9a were both present on granulocytes and monocytes. The clinical relevance of these antigens is discussed.

Antigens, Surface↗

Morphological studies on cellular detachment induced by antibody reactions directed against membrane associated antigens. An ultrastructural study.

The skin explant model was used to determine the effect of antibody reactions against membrane associated antigens on normal human keratinocytes. Addition of specific allo-antibodies against HLA class I antigens induced characteristic changes in the cells on the outermost region of the explant-outgrowth. A disorganization of the filopodia of these cells occurred and the edges of the cellular border were lifted from the substratum. These signs of detachment were also found when pemphigus serum was added. In both experimental conditions the detachment of the cells was complement independent. After removing the antiserum a recovery took place, but the cells once lifted from the substratum remained recognizable as a ridge of cells. No changes were observed when the explants were incubated with antibodies against HLA class II antigens. Incubation with specific antibodies against HLA class I antigens not present on the explant had also no effect. We propose that antibody reactions against various membrane associated antigens can induce within a few hours characteristic changes of the cellular margins.

Animals↗

The interaction between gamma-type endorphins and HLA class I antigens.

The clinical response of schizophrenic patients to treatment with gamma-type endorphins was found to be associated with certain HLA class I antigens (Bw22, B15, B13). Moreover, pretreatment of lymphocytes from healthy donors with des-Tyr1-gamma-endorphin (DT gamma E) inhibits the complement-dependent cytotoxicity between alloantisera and those HLA antigens, of which the frequency was increased among schizophrenic patients, who respond well to the gamma-endorphin therapy. Also for the opiate antagonist, naloxon interactions with HLA class I antigens could be demonstrated. Using the inhibition assay with DT gamma E it was possible to detect a subtype of HLA-A2, which, until now, was only defined by cytotoxic T lymphocytes and biochemistry. These data suggest an interaction between the HLA class I antigens and the receptor(s) for DT gamma E and naloxon, which may support the hypothesis that HLA class I antigens play a role in many recognition processes. Their role in immunological recognition would then be only a specialized form of a more general function.

Antigen-Antibody Reactions↗

Agranulocytosis induced by propylthiouracil: evidence of a drug dependent antibody reacting with granulocytes, monocytes and haematopoietic progenitor cells.

A patient with agranulocytosis and myeloid marrow hypoplasia following a second exposure to propylthiouracil (PTU) was studied for antibodies against mature blood cells and bone marrow precursor cells. During the acute phase of the agranulocytosis, significant growth inhibition of the myeloid committed progenitor cells (CFU-GM) was found following incubation with complement, indicating the presence of in-vivo cell bound cytotoxic antibodies. Using immunofluorescence and complement dependent cytotoxicity techniques it was demonstrated that acute phase and recovery phase sera contained circulating antibodies, reactive not only with differentiated granulocytes and monocytes but also with myeloid and erythroid (BFU-E/CFU-E) progenitor cells. Complement dependent lysis of the progenitor cells was facilitated by preincubation with PTU. These results indicate that the agranulocytosis was mediated by a PTU dependent antibody that affected both mature blood cells and bone precursor cells.

Aged↗

Destructive and protective effects of antibody on transplants in humans: practical and theoretical considerations.

Clearly the pioneering studies on hyperacute rejection, which lead to the concept of antibody-mediated injury to transplants, still present challenges to the clinician today. It is obvious that tests for antibodies before and after transplantation must be further refined to more reliably distinguish among destructive, protective and innocuous antibodies. The current crossmatch tests detect antibodies to donor lymphocytes, but lymphocytes may not always represent adequately the antigenic composition of the tissue that will be transplanted. Moreover the distribution of antigens in transplanted tissues must be considered in relation to the functional anatomy of the organs in order to understand the ultimate effects of antibodies on specific transplants. Thus some antibodies that produce a positive crossmatch may be safely ignored because they exert either a beneficial or no effect on the organ that is to be transplanted, while other antibodies that remain undetected by crossmatches on lymphocytes may damage some types of transplants. Moreover, the balance between protective and destructive antibodies is not dynamic; with time potentially dangerous antibody responses may be inhibited by a variety of autoregulatory mechanisms, some of which may be mediated by antibodies. Regulatory as well as cytotoxic antibody production may be actively stimulated by pretransplant blood transfusions. These antibody-mediated immune responses probably are magnified in the clinical setting by our current therapeutic immunosuppressive drugs which have more impact on cell-mediated immunity than on antibody-mediated mechanisms. New immunosuppressive interventions devised to inhibit undesired antibody-mediated immune responses might be of benefit to those patients who fail to respond to current rejection therapy as well as to patients who have pre-existing antibodies and are waiting for transplants.

ABO Blood-Group System↗

Comparison of techniques for the detection of monocyte specific antigens.

Monocyte specific antigens are relevant in renal and bone marrow transplantation, but a reproducible monocyte-antigen system has not yet been recognized. In order to establish a sensitive test system with reproducible results in monocyte serology, 3 different monocyte cytotoxicity techniques were compared. In our hands the two-colour fluorescence test on post-Ficoll total leukocyte suspensions fulfilled the criteria. This technique was used to screen sera from multiparous women and renal transplant recipients for the presence of monocyte specific antibodies. By testing sera on cells from individuals who were HLA compatible with the serum donors, anti-HLA reactions were excluded. Several promising sera containing monocyte specific antibodies were identified, thus indicating the success of our approach.

Antigens↗

Interaction between des-Tyr1-gamma-endorphin and HLA class I molecules: serological detection of an HLA-A2 subtype.

Preincubation of lymphocytes with des-Tyr1-gamma-endorphin (DT gamma E) inhibits the reaction between some HLA alloantisera and their corresponding antigens. One HLA-A2-specific antiserum was found which could detect a subtype of the HLA-A2 antigen on DT gamma E-treated lymphocytes from some donors. Comparison with the HLA-A2 subtypes as defined by a combination of cytotoxic T lymphocyte typing and biochemistry showed a complete correlation with the previously described HLA-A2.3 subtype.

Cytotoxicity Tests, Immunologic↗