Biomedical subjects

R Hoekzema

Publications and source records attributed to R Hoekzema.

41 records · Page 3Linked to original sources

PubMed1990

Aqueous humor interleukin-6 levels in uveitis.

The level of Interleukin-6 (IL-6) in the aqueous humor of 24 patients with 2 types of uveitis was measured with a specific bioassay using the murine hybridoma cell line B9. Sixteen patients had Fuchs' heterochromic cyclitis (FHC) and 8 had toxoplasma uveitis (TU). Sixty-three percent of each of the FHC and TU groups had raised levels of IL-6 in their aqueous (mean: 543 and 19,228 units/ml respectively). Thirteen control aqueous samples, obtained at surgery for senile cataract, showed IL-6 levels of less than 10 units/ml. Serum obtained at the same time as each aqueous humor sample also showed IL-6 levels of less than 10 units/ml, indicating that the raised levels of IL-6 found in the aqueous of uveitis patients did not result from serum leakage, but from local production. This is the first report on intraocular IL-6 levels, and indicates that IL-6 may play a role as an inflammatory mediator in uveitis.

Adolescent↗

PubMed1990

Humoral and cell-mediated immune response against human retinal antigens in relation to ocular onchocerciasis.

Autoimmune mechanisms are thought to be involved in the pathogenesis of the chorioretinal changes in ocular onchocerciasis. The humoral autoimmune response was determined by measuring serum levels of autoantibodies, directed against human S-antigen and interphotoreceptor retinoid binding protein (IRBP) using an enzyme immunoassay. The cell-mediated immune response to these antigens and a crude retinal extract was investigated by means of a two-step migration inhibition factor assay. Patients with onchocerciasis (n = 50) were subdivided into three groups: 1. without ocular involvement (n = 10), 2. with ocular onchocerciasis limited to the anterior segment (n = 19), 3. with onchocercal chorioretinopathy (n = 21). A group of endemic controls from Sierra Leone, West Africa were also studied. The cellular immune response to Concanavalin A was measured to assess the general capacity of lymphocytes to respond to a mitogen. High levels of anti-human S-antigen and IRBP antibodies were detected in patients with onchocerciasis and endemic controls. The levels of both anti-human S-antigen and IRBP antibodies were significantly higher in onchocerciasis patients compared to endemic controls (Mann-Whitney ranksum test; p less than 0.001 respectively 0.002). No relationship could be demonstrated between the anti-retinal antibody level and the occurrence of chorioretinitis in ocular onchocerciasis. The occurrence of the anti-retinal antibodies as a result of crossreactivity of anti-retinal antibodies with parasitic antigens or of induction of polyclonal B-cell activation due to parasitic infection is discussed, since high antibody levels were also found in patients with Bancroftian filariasis from Papua New Guinea and Surinam. The migration inhibition factor assay, in which the cell-mediated immune response to human S-antigen, IRBP and retinal extract was tested, showed that four out of 50 (8%) patients with onchocerciasis and four out of 25 (16%) endemic controls reacted with at least one retinal antigen. From the patients with onchocercal chorioretinopathy two out of 21 (10%) showed a positive cellular response. The general mitogen response tested with Con A was positive in all these individuals. In conclusion, circulating antibodies against human S-antigen or human IRBP are thus nor specific for onchocerciasis and in themselves not sufficient to cause chorioretinopathy in onchocerciasis, although their pathogenic role in an ongoing chorioretinitis cannot be excluded. Furthermore a role for a cell-mediated anti-retinal autoimmune mechanism in the pathogenesis of chorioretinitis in onchocerciasis as studied with human S-antigen, IRBP or crude retinal extract could not be demonstrated.

Antigens↗

PubMed1989

Biosynthesis of normal and low-molecular-mass complement component C1q by cultured human monocytes and macrophages.

High levels of low-molecular-mass complement component C1q (LMM-C1q), a haemolytically inactive form of C1q, are found in serum of individuals with inherited complete (functional) C1q deficiency and in serum of patients with systemic lupus erythematosus, whereas lower levels are present in normal serum [Hoekzema, Hannema, Swaak, Paardekooper & Hack (1985) J. Immunol. 135, 265-271]. To investigate whether LMM-C1q is a (by-)product of C1q synthesis or the result of degradation of C1q, cultures of blood monocytes and of alveolar macrophages, which secrete functional C1q, were studied. A considerable portion of C1q-like protein secreted by these cells was found to be LMM-C1q. In contrast with the C1q fragments that resulted from degradation of normal C1q during phagocytosis, culture-derived LMM-C1q appeared to be identical with LMM-C1q found in serum, as judged by sedimentation behaviour, subunit structure and recognition by poly- and mono-clonal antibodies raised against C1q. The presence of LMM-C1q in cytoplasmic organelles compatible with the Golgi apparatus and the inability to generate LMM-C1q by impeding hydroxylation and triple-helix formation of C1q further argues against degradation as its source. Monocyte cultures of homozygous probands from two families with complete functional C1q deficiency reflected the abnormalities in serum, i.e. absence of functional C1q, but increased levels of LMM-C1q. By contrast, secretion of C1q and LMM-C1q by cells from healthy individuals was clearly co-ordinate, indicating that LMM-C1q in serum may provide a unique marker of C1q synthesis in vivo.

Cells, Cultured↗

PubMed1988

The distortive mechanism for the activation of complement component C1 supported by studies with a monoclonal antibody against the "arms" of C1q.

A mouse monoclonal antibody (IgG1 isotype) against human C1q (MAb 130) is presented that activates C1 in serum through its antigen-binding sites at an optimal molar ratio of 3 MAbs:1 C1q. The antibody does not inhibit binding of C1q to IgG. Experiments with pepsin- and collagenase-digested C1q showed that MAb 130 binds to the fibril-like strands (arms) of C1q, close to the globular heads. Bivalency of MAb 130 was a requirement for C1-activation, but not for binding to C1q. Increasing the segmental flexibility of the intact antibody by reduction and alkylation destroyed its capacity to activate C1. A MAb against the globular heads of C1q completely inhibited C1-activation by aggregated IgG (AHG), but did not prevent activation by MAb 130. C1, reconstituted by adding C1q-stalks that lack the globular heads to C1q-depleted serum was not activated by AHG, whereas activation by MAb 130 was not affected. Activation of serum-C1 by AHG and MAb 130 was inhibited by addition of excess purified C1-inhibitor in a comparable and dose-dependent manner. Sucrose-gradient analysis indicated a predominance of stable complexes of a single C1q-molecule with three MAbs at the optimal activating ratio. When isolated and added to C1q-depleted serum, these complexes activated C1 efficiently. A mechanism for activation by MAb 130 is proposed that supports the "distortive" model of C1-activation.

Antibodies, Monoclonal↗

PubMed1985

Low molecular weight C1q in systemic lupus erythematosus.

In sera of patients suffering from an exacerbation of systemic lupus erythematosus (SLE), increased amounts of abnormal C1q were detected, contrasting with decreased or even undetectable levels of normal C1q in these sera. When analyzed immunochemically by double immunodiffusion, this low m.w. C1q (LMW-C1q) appeared to be identical with the defective C1q in serum of individuals with an inherited, homozygous inability to produce functional plasma C1q. These persons show a tendency to develop SLE-like syndromes. Like the genetically defective C1q, the abnormal C1q molecule in SLE sera was hemolytically inactive, did not incorporate in C1, was found in the supernatant of euglobulin-precipitated serum, and appeared in the break-through fraction of a cation-exchange column. Sucrose gradients and gel filtration analyses supported the putative identity of the molecules. SDS-PAGE and immunoblots revealed the presence of subunits that reacted with antibodies against C1q and confirmed the C1q-like nature of LMW-C1q. Low levels of LMW-C1q were also detected in serum and plasma of normal individuals. A radial immunodiffusion technique was used to measure LMW-C1q in the serum of 54 patients. Although these patients were not selected for parameters of disease activity, their levels of LMW-C1q were significantly higher than those of normal individuals and children with decreased C3 levels due to acute glomerulonephritis.

Centrifugation, Density Gradient↗