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J Neppert

Publications and source records attributed to J Neppert.

At least 55 records · Page 3Linked to original sources
PubMed1989

[Antibodies, clinical and hematologic findings in immunoneutropenias].

Sera were analyzed from patients who were suspected to have antibodies to neutrophils. The analysis comprised five methods which avoid heterologous antibodies to human immunoglobulin. These methods were the granulocyte agglutination test (GAT), the granulocyte cytotoxicity test (GCT), the monocyte cytotoxicity test (MCT), the lymphocyte cytotoxicity test (LCT) and immune phagocytosis inhibition test (IPI). Each serum was tested with cells from five healthy donors, at least, and some with cells from relatives. After exclusion of sera containing multiple antibodies and HLA-antibodies with positive LCT- and IPI-tests, the GAT- or GCT-reactive antibodies were significantly (p = 0.00005) more frequent among patients with neutrophil counts less than or equal to 1.0 X 10(9)/l (30%; n = 117) than among patients with neutrophil counts greater than 1.0 X 10(9)/l (9%; n = 111). Within the group of neutropenic patients (less than or equal to 1.0 X 10(9)/l) these antibodies were significantly (p = 0.001) more frequent in patients without (48%; n = 46) than with reduction of the granulopoiesis (13%; n = 31). This typical feature of an immune cytopenia also could be shown with GAT-reactive antibodies alone. From all five antibody tests the diagnostic criteria of the autoimmune neutropenia (AINP) and neonatal alloimmune neutropenia (NIN) were infered. 25 patients with clearly defined AINP presented with significantly more infectious complication than 23 patients with only assumed AINP (48% versus 13%). Further, the clinical findings of eight patients with NIN were described. --Antibodies only reactive in the GAT were detected in healthy individuals (1.3%; n = 75) and patients without indication for AINP or NIN (8%; n = 111), also.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Pregnancy-maintaining antibodies: workshop report (Giessen, 1988).

To analyse the nature of antibodies which are purported to be essential for the maintenance of normal human pregnancy, six centers participated in a workshop of "blind" tests on 19 allosera. Fc-receptor dependent assays detected antibodies with specificity only for HLA. In addition to cytotoxic antibodies, the Fc-receptor dependent immune phagocytosis inhibition test revealed two non-cytotoxic alloantibodies with HLA specificity. These antibodies had high titers and may, therefore, be essentially non-cytotoxic. Murine monoclonal antibodies to HLA-A, B, C or DR (W6/32 and 2MC3) were used to evaluate the methods. These antibodies inhibited immune rosette formation as well as immune phagocytosis. Diluted to concentrations below the threshold of complement-dependent cytotoxicity, the monoclonal antibodies still inhibited the mixed lymphocyte reaction and the immune phagocytosis. A human monoclonal immunoglobulin M with specificity for monomorphic non-HLA lymphocyte antigens inhibited the mixed lymphocyte reaction. The immune rosette inhibition test exhibited several false positive reactions, e.g. three out of four with a serum that did not contain alloantibodies to blood cells. Non-cytotoxic antibodies were therefore rare in the selected sera of the workshop and they exhibited HLA specificity only. No participant was able to identify pregnancy-maintaining non-HLA-antibodies.

Abortion, Habitual↗
PubMed1989

Influence of immunization with allogeneic spleen cells on the number of viable neonates in mice.

Female CBA/J (H-2k) mice mated with male DBA/2J (H-2d) mice show a high level of fetal resorption, which can be reduced by immunization with BALB/c (H-2d) spleen cells. The morphologically defined fetal resorption rate upon which evaluation of the outcome of pregnancy has previously been based in this strain combination is not equivalent to the rate of production of viable neonates.

Abortion, Habitual↗
PubMed1989

[Diagnosis in patients with habitual abortion].

Since promising immunological concepts for treatment of patients with three or more miscarriages have been introduced, an exact clarification of all possible etiological factors has become even more urgent, because an infection risk associated with leucocyte therapy cannot be ruled out. Own experiences with 47 couples with a history of habitual abortion who had been diagnostically evaluated in a special screening program in our hospital between 1985-1988 are discussed in the light of surveys of the recent literature. A critical revision of several factors which had been classified as etiological factors of habitual abortion in the past, seems important. While genetic factors are undoubtedly the most important cause of miscarriages in the first trimenon, the role of anatomical uterine anomalies (amongst our patients in 7 per cent), luteal insufficiency (among our patients in 9 per cent) and endometriosis cannot be evaluated with certainty yet because different diagnostic criteria have been established for diagnosis in the literature. Based on newly published data immunological factors seem to become etiologically more important; other anomalies, like infections or diabetes do not seem to be associated with an increased risk for habitual abortion. According to our experiences, habitual abortion may present as a problem involving different pathogenetic factors (among our patients in 79 per cent) so that sequential therapeutic steps may be required for treatment of a-possibly-multifactorial disease.

Abortion, Habitual↗
PubMed1989

Prevention of recurrent spontaneous abortion by intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) treatment was attempted as a novel therapeutic approach for unexplained recurrent spontaneous abortions (RSA) occurring in the first trimester of pregnancy. Twenty women with a history of RSA were treated with IVIG during pregnancy. Therapy was commenced at week 5 of gestation with 1 dose of 0.5-0.6 g IVIG/kg body weight. Infusions were repeated every 3 weeks (0.3-0.4 g/kg) and terminated by week 22 to 24. Of 20 women, 11 delivered healthy infants at term. 5 women are still pregnant, 3 in the third trimester. Only 3 patients suffered abortions and 1 presented with ectopic pregnancy. The overall success rate was 82-86%. Thus, the therapeutic effect of IVIG is comparable to that of the conventional transfusion/vaccination regimen with allogeneic leukocytes, but avoids the risk of transmission of infections and/or HLA immunization, has no major adverse effects and is applicable to 'nonresponders'.

Abortion, Habitual↗
PubMed1988

Reduced immune phagocytosis of monocytes from neonates whose mothers produce HLA antibodies.

In vivo immune phagocytosis of neonatal monocytes was significantly correlated to the extent of maternal HLA immunization. Monocytes from all 15 neonates of mothers with HLA antibodies show reduced immune phagocytosis. In contrast, this holds true for monocytes from only 6 out of 13 neonates of mothers without detectable HLA antibodies. We infer the hypothesis that maternal HLA antibodies bind to mononuclear phagocytes of the fetus and of the fetal part of the placenta and thus cause inhibition of immune phagocytosis. Thereby, activation and secondary cell or tissue injury will not ensue and rejection of the fetal allograft is prevented in those pregnancies in which maternal alloimmunization occurs.

Female↗
PubMed1987

Detection of antibodies specific for HLA-A,B,C,DR,DQ and DP by the erythrocyte antibody rosette inhibition (EAI) and immune phagocytosis inhibition (IPI) tests.

Two methods for the detection of murine monoclonal antibodies against determinants of the human major histocompatibility complex (MHC) were evaluated. These methods are based upon the function of Fc receptors; the erythrocyte antibody rosette inhibition test (EAI test) using B-lymphocytes and the immune phagocytosis inhibition test (IPI test) using monocytes. Compared to the EAI test the IPI test was technically easier and gave better discrimination between positive and negative results. The inhibition by antibodies of monomorphic class II MHC or polymorphic HLA-DR antigens was stronger in the IPI than in the EAI test. Antibodies against HLA-DQ and DP antigens evoked inhibition only using the EAI test. Using IgG derived from placenta in different dilutions the detection of its anti-HLA antibodies was more readily achieved in the IPI test than in the EAI test.

Antibodies, Monoclonal↗
PubMed1987

Persistence and selectivity of the immune phagocytosis inhibition by major histocompatibility complex antibodies.

Major histocompatibility complex (MHC) antibodies induce immune phagocytosis inhibition (IPI) which lasts for at least 7 days. IPI-inducing antibodies do not inhibit the phagocytosis mediated by the beta-glucan receptor. This corresponds well to recent findings that these antibodies do not interfere with the phagocytosis of deactivated saccharomyces, mediated by the mannose-fucose receptor, or polyacrylic acid particles, also mediated by non-Fc receptors. Substances that interact with certain MHC antigens or with Fc receptors, certain toxins that inhibit surface molecule mobility, and ciclosporin do not cause IPI and do not suppress the induction of IPI by MHC antibodies. These substances are: opioid peptides, insulin, penicillin G, immune complexes, aggregated IgG, Fc fragments, ciclosporin, botulinum C2 toxin, sodium azide. Some lectins and EDTA are inhibitory in a non-selective fashion, since the Fc receptor independent phagocytosis is also abrogated.

Antibodies, Monoclonal↗
PubMed1986

Immune phagocytosis inhibition by commercial immunoglobulins.

Sixteen commercially available immunoglobulins (Ig) and 5 anti-Rho (D) hyperimmune globulins were investigated for immune phagocytosis inhibition (IPI) factors as well as for T, B lymphocytotoxic and monocytotoxic antibodies. All Ig contained IPI factors with lowest inhibitory IgG concentrations ranging from 0.08 to 50 mg/ml. Pepsin-digested Ig was noninhibitory. IPI factors in anti-D preparations were uniformly high (inhibitory IgG concentrations 0.6-2.5 mg/ml). Cytotoxic antibodies against T, B lymphocytes and monocytes were found in 2,2 and 7 products, respectively. Since we have recently shown that IPI is caused by antibodies against major histocompatibility complex antigens, most likely HLA, the hypothesis is put forward that IPI factors in Ig are HLA-related, cytotoxic as well as noncytotoxic antibodies which act via Fc receptor blockade of human monocytes.

B-Lymphocytes↗
PubMed1986

Insignificant immune phagocytosis inhibition and cytotoxicity by the murine monoclonal HLA-DP antibody B7/21 tested on human monocytes and macrophages.

On the basis of fluorescence flow cytometry data with the monoclonal antibody (MoAb) B7/21, and of the differing cell sizes, the HLA-DP antigen density on monocytes is estimated to be 25% of that on B lymphocytes. The remote positions of the antigens are assumed to be responsible for the markedly reduced inhibitory capacity of the MoAb B7/21 in immune phagocytosis by monocytes and for the absence of complement-dependent cytotoxicity of this MoAb to monocytes. The findings from experiments on peritoneal macrophages are comparable. Therefore HLA-DP may not be important for the functioning of the monocytes and macrophages.

Antibodies, Monoclonal↗
PubMed1986

Inhibition of immune phagocytosis by human sera with HLA A, B, C and DR but not with DQ or EM type reactivity.

613 sera from pregnant women were investigated for inhibition of immune phagocytosis (IPI) by monocytes exposed to anti-D (Rh)-sensitized human red blood cells. IPI was detected in 42 (26%) of 165 and in 78 (17%) of 448 sera assessed against monocytes from 15 or 5 panel donors, respectively. All IPI-positive sera reacted in an allotypic pattern. Eight IPI-positive sera tested with autologous monocytes were found to be nonreactive. Upon comparative analysis of 448 sera, a significant correlation was found between the specific patterns of IPI and lymphocytotoxicity by HLA antibodies. In addition, 13 sera (4%) were positive for IPI, but not for lymphocytotoxicity. Twenty IPI-positive sera were tested by indirect immunofluorescence against platelets and T lymphocytes and revealed IgG antibodies in 16 and 11 sera, respectively. IPI activity could be removed from 8 out of 10 positive sera by platelet pool absorption. While virtually all sera exhibiting HLA, A, B or C-like activity (cytotoxicity with all cells) or HLA DR-like activity (exclusive cytotoxicity with B lymphocytes and monocytes) were IPI-positive, IPI was infrequently observed with sera containing HLA DQ-like activity (cytotoxicity with B lymphocytes only). IPI was also rarely seen with sera cytotoxic only to monocytes and not at all with sera containing antibodies against endothelial/monocyte antigens. We conclude that IPI is caused by cytotoxic as well as noncytotoxic HLA A, B, C, DR-specific antibodies. This effect may bear significance for the maternal immune response against fetal antigens and may be useful for pretransplant histocompatibility testing.

Adult↗
PubMed1986

Binding of murine monoclonal antibodies to human MHC class I or II antigens increases binding sites for either antibody.

Membrane redistribution of major histocompatibility complex (MHC) class I and II antigens on human B lymphocytes and monocytes was studied quantitatively by fluorescence flow cytometry using monoclonal antibodies (mAb) w6.32 (class I-specific) and 2MC3 (class II-specific). It was shown that the surface density of class I and II antigens to which corresponding mAb had been bound decreased rapidly upon incubation at 37 degrees C. However, the total amount of class I antigens remained practically unchanged, while that of class II antigens increased substantially. This augmentation of class II antigens could be elicited not only by the corresponding class II-specific mAb but, similarly, also by non-corresponding class I-specific mAb. New expression of class I antigens only compensated for removed antigens. The speed of disappearance was comparable for antigens of either class. We conclude that the more pronounced expression of new class II antigens is not due to a greater surface mobility, but to a faster recycling and/or larger intracellular deposits of the antigens. This uneven redistribution of class I and II antigens is likely to reflect differences of function known to be dependent on MHC products.

Animals↗