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Biomedical subjects

R Matre

Publications and source records attributed to R Matre.

At least 55 records · Page 3Linked to original sources

Fc receptors for IgG on cultured human microglia mediate cytotoxicity and phagocytosis of antibody-coated targets.

We have utilized surgically resected human central nervous system (CNS) tissue to determine the expression and functions of Fc receptors (Fc gamma R) on individual cell types found within the CNS. We observed all three classes of Fc gamma R on microglial cells in situ and in vitro, but not on astrocytes or oligodendrocytes. Incubation of cultured microglia with immune complexes (antibody-coated red blood cells) induced phagocytosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and oxidative bursts. We also found that microglia have the capability to produce T cell stimulatory soluble mediators after Fc gamma R crosslinking. These functional responses were enhanced by pretreatment of the microglia with interferon-gamma (IFN-gamma). Our results implicate microglial effector responses triggered by interaction of Fc gamma R with opsonized antigens as potential mediators of tissue injury within the CNS. Such injury may be particularly applicable to multiple sclerosis, an inflammatory demyelinating disease characterized by intrathecal production of immunoglobulins and cytokines.

Adult↗

Fc gamma-receptor activity of placental annexin II.

We have previously produced a MoAb, B1D6, against a placental FcR. The antigen isolated using F(ab')2-fragments of B1D6 exhibits Fc-binding properties with low affinity for IgG. The antigen is a single-chained glycoprotein with a molecular weight of approximately 37 kDa and a pI of about 7.0-8.5. Amino acid sequences from enzymatic digests of the antigen indicated that it is annexin II. Immunoreactivity using anti-annexin antisera and purified placental annexin II have further established the specificity of B1D6 to annexin II. The B1D6 epitope appears to be intramembraneous and intracellular on placental syncytiotrophoblasts, monocytes and other cells investigated.

Amino Acid Sequence↗

Epithelial expression of HLA class II antigens and Fc gamma receptors in patients with adult periodontitis.

The distribution of HLA class II (DR, DP, DQ) and Fc gamma R (I, II, III) was analyzed in the epithelia of patients with advanced marginal periodontitis using cryostat sections incubated with monoclonal antibodies (MoAb) against the Langerhans cell (LC) (CD1a) and various subtypes of HLA class II and Fc gamma R, and the indirect immunofluorescence technique. In the oral gingival epithelium (OGE), LC were concentrated subjacent to the connective tissue papillae, while in the pocket epithelium (PE), they were most abundant at the gingival margin. HLA-DP, DQ, and DR stained LC in both OGE and PE. HLA-DQ+ LC were significantly fewer than DP+ and DR+ LC. HLA-DR also stained keratinocytes (KC) in the whole extension of both OGE and PE. HLA-DP was also observed on KC, but not HLA-DQ. Fc gamma R II stained both LC and focal areas of KC. In PE FC gamma R II+ LC were concentrated near the bottom of the pocket, while in the OGE, they were concentrated at the gingival margin. Fc gamma R III was present only on KC, especially in the basal and suprabasal layer. The results indicate that the epithelial cells are actively involved in the development and maintenance of the inflammation of periodontal disease.

Adult↗

Identification of a soluble Fc gamma-binding molecule (annexin II) in human serum using a competitive ELISA.

We have previously produced a monoclonal antibody (mAb), B1D6, reactive with a 37 kD placental IgG Fc-binding molecule (FcR), recently identified as annexin II. Annexin II is an intracellular molecule found in several cell types, including endothelium and monocytes. Since soluble Fc-binding molecules are of importance in the regulation of the immune response, we have now used B1D6 in a competitive ELISA to study levels of soluble annexin II in human sera. Soluble annexin II was detected in all sera studied. The highest levels were observed in patients with infectious mononucleosis. Gel filtration of sera revealed annexin II in fractions corresponding to a molecular weight of 40-60 kD. In Western blot analysis a molecule of approximately 37 kD was found. The pI of soluble annexin II was about 7.5-8 as demonstrated by chromatofocusing. Annexin II belongs to a family of phospholipid-binding molecules involved in anti-inflammatory responses, and elevated levels of annexin II in serum may be important for the suppression of an immune response.

Annexin A2↗

Ryanodine receptor antibodies related to severity of thymoma associated myasthenia gravis.

Ryanodine receptor (RyR) antibodies are detected in about 50% of patients with myasthenia gravis who have a thymoma. The RyR is a calcium release channel involved in the mechanism of excitation-contraction coupling in striated muscle. In this study the severity of myasthenia gravis assessed by a five point disability score was compared between 12 patients with myasthenia gravis, a thymoma, and RyR antibodies and 10 patients with myasthenia gravis and a thymoma but without such antibodies. Symptoms of myasthenia gravis were significantly more severe in patients with RyR antibodies. The mean (SD) disability scores were 3.7(0.5) in patients with antibodies and 2.7 (0.9) in those without at peak of illness, (p = 0.01) and 3.4(1.4) v 1.6(0.7) at the end of an average observation period of five years (p = 0.002). The number of deaths due to myasthenia gravis was five of 12 RyR antibody positive patients, and none of 10 RyR antibody negative patients (p = 0.04). RyR antibody levels correlated positively with severity of myasthenia gravis. The presence of circulating RyR antibodies seems to be associated with a severe form of thymoma associated myasthenia gravis.

Adult↗

Serum levels of interferons and TNF-alpha are not correlated to psoriasis activity and therapy.

Sera from 52 patients with psoriasis and 106 controls were tested for IFN-tau, IFN-alpha 2 and TNF-alpha in ELISA and for total IFN activity using an infectivity inhibition micromethod. Psoriasis patients had lower serum levels of IFN-tau than had the controls: median 0.10 ng/ml vs. 0.16 ng/ml (p = 0.01). The highest median serum IFN-tau levels were in patients with peripherally spreading psoriasis, 0.10 ng/ml, and acute guttate psoriasis, 0.09 ng/ml. Patients with stable plaque psoriasis had lower serum IFN-tau levels (median 0.0) than those with other forms of psoriasis, or blood donors. The serum levels of IFN-alpha 2, total IFN activity and TNF-alpha did not differ between the psoriasis and control group. Treatment with cyclosporin, acitretin and the Goeckerman regimen increased the total IFN activity, but did not affect the levels of IFNs nor TNF-alpha.

Acitretin↗

IgG-Fc receptors in stratum granulosum: an immunological defence in human skin?

Receptors for the Fc-part of IgG (Fc tau R) in stratum granulosum of normal human skin were examined using cryosections and indirect immunofluorescence staining with 1) soluble immune complexes and 2) monoclonal antibodies (MoAbs) against different types of Fc tau R, i.e. 32.2 (anti-Fc tau I-CD64), IV.3 (anti-Fc tau RII-CD32) and Leu 11b (anti-Fc tau RIII-CD16). The immune complexes gave staining corresponding to stratum granulosum in sections from all skin specimens. Inhibition experiments showed that pre-incubation of the sections with monomeric and heat-aggregated human IgG, periodic acid and formaldehyde inhibited the immune complex binding. F(ab')2 containing immune complexes did not bind to the skin sections. The MoAb 32.2 gave granular and Leu 11b linear staining corresponding to stratum granulosum. In addition, both IC, 32.2 and Leu 11b gave weaker staining of keratinocytes in other parts of the epidermis. IV.3 stained epidermal Langerhans' cells and were unreactive with other epidermal cells. Indirect immunofluorescence staining with MoAbs against IgG subclasses showed the presence of all IgG subclasses in stratum granulosum. The results show that granulosum cells express both high- and low-affinity IgG receptors and in vivo bound IgG. The data point to a role for stratum granulosum in cutaneous immunity.

Antibodies, Monoclonal↗

In situ characterization of leukocytes in the fallopian tube in women with or without an intrauterine contraceptive device.

Histological evaluation of sections from the human fallopian tube revealed an inflammatory reaction in 21 of 31 women using an intrauterine contraceptive device (IUCD) and in four of 29 controls (non-IUCD users). The inflammatory cells were mainly localized at the epithelium-lamina propria interface and at the center of the mucosal folds. The immunohistochemical study revealed leukocytes (CD45+), T lymphocytes (CD3+), T helper cells (CD4+), T suppressor/cytotoxic cells (CD8+), B lymphocytes (CD22+, CD19+), granulocytes, monocytes and null cells (CD11b+) mainly localized at the lamina propria in both groups. T lymphocytes were the predominant cell type, and the ratio between T helper and T suppressor/cytotoxic cells was fairly close to one both in IUCD-users and controls. B lymphocytes were the least frequent cell type identified. In IUCD users, the numbers of the different leukocytes were increased. In both groups, IgA-, IgG- and IgM-positive cells were demonstrated and were predominantly located at the lamina propria of the mucosal folds. The IgA-positive cells dominated in both groups, whereas IgG- and IgM-positive cells were less frequent. Cell positive for IgA, IgG or IgM were significantly increased in number in the IUCD users. The data confirm the presence of an immune system in the normal human fallopian tube and indicate that the IUCD can induce a prominent recruitment of inflammatory cells, with a tubal inflammation as the result. The IUCD may disturb the immunological function of the fallopian tube and its rôle in fertilization.

Adult↗

Anti-cardiac ryanodine receptor antibodies in thymoma-associated myasthenia gravis.

Sera from myasthenia gravis (MG) patients with thymoma were examined in Western blot for the presence of antibodies to proteins in the sarcoplasmic reticulum (SR) of cardiac muscle. Fourteen of 30 MG thymoma sera had IgG antibodies to a protein with the same electrophoretic mobility as cardiac muscle ryanodine receptor (RyR). Anti-cardiac RyR antibodies were not detected in any of the 45 sera from MG patients without thymoma. The same 14 MG thymoma sera, but none of the others, bound to RyR from skeletal muscle as well. Neutralization experiments showed that the anti-RyR antibodies in MG patient cross-reacted with cardiac and skeletal muscle RyR. Since skeletal and cardiac muscle RyRs are antigenically different, our findings may indicate that autoantibodies to RyR in MG originate by sensitization to a peptide shared by cardiac and skeletal muscle RyR, rather than to the complete native RyR.

Autoantibodies↗

The expression of CD59 in normal human nervous tissue.

The expression of CD59, a complement regulator of the formation and function of the terminal cytolytic membrane attack complex, was studied in human normal nervous tissue by immunohistochemical markers using two monoclonal antibodies 1F5 and MEM43. CD59 was present on Schwann cells, neurons and endothelial cells in the peripheral nervous system (PNS), and on Schwann cells in culture. In the central nervous system (CNS) CD59 was found predominantly on endothelial cells. There was also a diffuse staining of white and grey matter of the spinal cord and brain, presumably of microglia, oligodendrocytes, astrocytes and neurons, as these cells were CD59 positive in culture. Furthermore, CD59 was detected in the cerebrospinal fluid (CSF) of healthy individuals. CD59 in the PNS and CNS was glycosyl-phosphatidylinositol linked and had a molecular weight of 19,000-25,000. The presence of CD59 on various cells of the nervous system and in the CSF suggests that regulation of complement activation by this protein is important in neural host defence mechanisms.

Adult↗

Serum immunoglobulin profiles in asymptomatic HIV-1 seropositive adults and in patients with AIDS in Dar es Salaam, Tanzania.

Serum levels of immunoglobulin classes and IgG subclasses were determined in healthy seronegative (n = 50) and in HIV-1 seropositive adults (n = 50) from Tanzania, a region with heterosexual HIV-1 transmission pattern. The mean levels of total IgG, IgG1, IgG3, IgA, IgM, and IgD obtained were found to be significantly higher in HIV-1 seropositive sera than in control sera. The mean IgA, IgM, IgD and IgG3 levels showed an increasing trend with progression from asymptomatic phase to AIDS phase. The mean levels for total IgG, IgG1 and IgG2 remained constant while that for IgG4 decreased with progression to AIDS phase. From the findings, it is concluded that polyisotypic hypergammaglobulinaemia and serum IgG subclass changes occur in HIV-1 seropositive individuals in Tanzania. The characteristic changes observed for IgD, IgG3 and IgG4 levels with evolution from asymptomatic to AIDS phases could be of value in monitoring disease progression.

Acquired Immunodeficiency Syndrome↗

Fc gamma-receptors in skin and serum from patients with psoriasis, before and after therapy.

IgG-Fc receptors (FcR) are present on most immune competent cells. We have examined FcR in skin lesions from 8 patients with stationary plaque psoriasis and 12 patients with highly active psoriasis using MoAbs against FcR and binding of soluble immune complexes. FcR in serum were measured in ELISA. The patients were treated with cyclosporin (n = 5), acitretin (n = 7) and Goeckerman regimen (n = 8). As controls served 8 skin biopsies and 22 sera from healthy individuals. Highly active psoriatic lesions showed strongest activity for FcRI, II and III and immune complex binding. The FcR+ mononuclear cells were located perivascularly and along the dermo-epidermal junction. The FcR activity decreased in correlation to the improvement following therapy. Epidermal Langerhans cells (LC) were positive for FcRII and immune complex binding. FcR activity on LC decreased during therapy. Keratinocytes expressed FcRI and III, irrespective of disease activity and therapy. FcR levels were lower in sera from psoriatics than in controls, median 0.15 vs. 0.27 (p < 0.01), and not correlated to disease activity. In 4 patients the FcR levels increased during therapy. The reduced levels of FcR in psoriatic sera might be due to consumption in the skin or anti-FcR autoantibodies.

Enzyme-Linked Immunosorbent Assay↗

IgG subclass distribution of ryanodine receptor autoantibodies in patients with myasthenia gravis and thymoma.

Patients with myasthenia gravis (MG) and thymoma often have autoantibodies to the ryanodine receptor (RyR), a ligand-gated Ca(2+)-release channel in the sarcoplasmic reticulum of striated muscle. Using an ELISA, we studied the Ig isotype and IgG subclass distribution of RyR autoantibodies in sera from 30 MG patients with thymoma. RyR IgG antibodies were detected in 16/30 sera. 14/30 sera had IgG1 RyR antibodies, and 15/30 sera had IgG3 RyR antibodies. All sera with IgG1 RyR antibodies also contained IgG3 antibodies. A small number of sera had low amounts of IgG2, IgG4, IgA or IgM RyR antibodies. The RyR autoantibodies are therefore mainly expressed in the IgG1 and IgG3 subclasses. The RyR autoantibodies may be of pathogenic significance by interfering with the mechanism of excitation-contraction coupling in striated muscle.

Autoantibodies↗

Suppression of mitogen-induced lymphoproliferation by soluble IgG Fc receptors in retroplacental serum in normal human pregnancy.

A competitive ELISA was used to quantify soluble IgG Fc receptors (FcR) in retroplacental serum (RPS) and peripheral serum (PS) from 10 women after uncomplicated full-term deliveries. The RPS contained significantly higher amounts of soluble FcR than did PS from the same individuals. RPS suppressed phytohaemagglutinin-stimulated lymphoproliferation as compared with PS, and a positive correlation (r = 0.66) was found between the degree of suppression and the difference in soluble FcR level between RPS and PS. Absorption of sera with Sepharose 4B coupled with heat-aggregated IgG strongly reduced the immunosuppressive activity, whereas absorption with Sepharose coupled with IgG F(ab')2 fragments did not. When IgG-binding material was eluted from Sepharose beads and added to cell cultures, the immunosuppressive activity was restored. The data indicate that soluble FcR at physiological levels have immunosuppressive properties. FcR-mediated immunosuppression may be of importance for maintenance of local immunosuppression during pregnancy.

Female↗

Demonstration of Fc gamma receptors in human endometrium.

Cryostat sections of human endometrium bound sheep erythrocytes (E) sensitized with rabbit IgG antibody (A), (EA). Unsensitized E were not bound. Native, heat-aggregated IgG and Fc fragments of IgG inhibited the binding of EA, whereas IgM, IgA and F(ab')2 fragments of IgG did not. The data indicate the presence of receptors for the Fc part of IgG (FcR). Using immune complexes of horseradish peroxidase (HRP) and rabbit IgG antibodies to HRP and monoclonal antibodies (mAbs), FcR were located to the glandular epithelial and endothelial cells, macrophages and predecidual cells of the stroma. These structures were also stained by mAbs against all three FcR classes and a 40-kD low affinity placental FcR. Preliminary results indicate that the expression of FcR varies during different stages of the menstrual cycle. FcR in the endometrium may play a rôle in local immunoregulation necessary for nidation and development of the blastocyst.

Adult↗

CR1 activity on erythrocytes and renal glomeruli in patients with renal disorders.

Complement receptors for C3b/C4b (CRI) on erythrocytes (ERC1) and renal glomeruli (GCR1) were examined in patients with different types of renal disorders. Normal ECR1 activity was found on erythrocytes from patients with IgA glomerulonephritis, benign nephrosclerosis and other types of renal diseases. In patients with systemic lupus erythematosus (SLE) and glomerulonephritis ECR1 activity was low or absent in 75% of the patients. The GCR1 activity, however, was normal except in areas with complement deposits where GCR1 activity was abolished. During treatment with corticosteroids and azathioprine of patients with SLE the clinical response was followed by increased functional ECR1 activity. In those patients who did not respond the ECR1 activity was persistently low. Three patients with renal transplant all showed increased ECR1 activity.

Erythrocytes↗