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Biomedical subjects

A Kijlstra

Publications and source records attributed to A Kijlstra.

At least 163 records · Page 9Linked to original sources

The influence of vitrectomy and lensectomy on experimental uveitis.

A secondary immune response in the rabbit eye can be provoked by intravenous injection of the antigen, previously injected intravitreally. The inflammation process consists of iris hyperemia, pericorneal redness and cellular and proteinous exudates in the anterior chamber and vitreous. The influence of vitrectomy combined with lensectomy or preceded by extracapsular lens extraction on the character of the secondary immune response has been studied in the rabbit eye. Both eyes of adult rabbits were injected intravitreally with human serum albumin. Five to ten weeks later, when the primary inflammation process had vanished, the vitreous and the lens were removed from the right eye in one group of animals. In a second group of rabbits, an extracapsular lens extraction was performed upon both eyes, later followed by vitrectomy of the right eye. Four weeks later all animals received an intravenous booster injection with human serum albumin. The eyes which still contained the vitreous developed a secondary inflammation consisting predominantly of cells and fibrin clots in the anterior chamber however without flare. On the contrary, the eyes which underwent vitrectomy developed a flare in the anterior chamber with only a few cells detectable. Analysis of cells and protein in the anterior chamber and histological evaluation supported the clinically observed differences between both eyes. These results suggest that the persistence of the vitreous is associated with the reactivation of a secondary immune response. Vitrectomy combined with lensectomy or preceded by extracapsular lens extraction leads to increased passive transfer of proteinous material through the vessels.

Animals↗

Cytokines and intraocular inflammation.

Although new endogenous mediators of inflammatory and immune responses are reported almost on a monthly basis, the cytokines IL-1, TNF, and IL-6 have emerged as the primary regulators of local inflammation in man. In this paper, uveitogenic and other properties of these particular cytokines are discussed and attention is payed to the possible involvement of a cytokine-network in the development of uveitis.

Animals↗

Serum antibody response to human and bovine IRBP in uveitis.

Interphotoreceptor retinoid binding protein (IRBP) is a 136,000 molecular weight photoreceptor cell protein capable of inducing an experimental autoimmune uveitis (EAU) in susceptible animal strains. The occurrence of serum antibodies against human (Hu) or bovine (Bo) IRBP was investigated in patients with uveitis and healthy controls. A sensitive ELISA detected anti-IRBP in approximately 50% of patients and controls, without apparent differences in the mean level, titre or avidity and irrespective of the origin of the antigen. Although the correlation (p less than 0.001) between anti-HuIRBP and anti-BoIRBP levels in uveitis sera suggested the presence of crossreacting antibodies, these sera also contained antibodies specific for either the human or the bovine antigen. The only difference between patients and controls was the greater ability of antibodies in uveitis sera (p less than 0.05) to recognize a synthetic peptide of HuIRBP, which induces severe EAU in rats. We conclude that autoantibodies to IRBP occur naturally in man and are not increased in patients with uveitis.

Amino Acid Sequence↗

Detection of secretory IgM in tears of IgA deficient individuals.

Tears from normal (n = 5) and serum IgA deficient (n = 3) individuals were investigated for the presence of secretory Immunoglobulin A (sIgA), sIgM and free secretory component (SC) by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) using 10-15% gradient minigels (PhastSystem), followed by immunoblotting using various immunological probes. Tear samples were treated in denaturing (SDS) sample buffer under non-reducing as well as reducing conditions, prior to analysis. All normal tear samples contained sIgA as well as free SC (estimated MW: 82kD) but only traces of IgM. Tears from the three serum IgA deficient subjects lacked sIgA but did contain free SC. In two of them sIgM was clearly detected and after treatment of tears with reducing agent, IgM (mu) heavy chain fragments (estimated MW: 78kD) were identified and could be distinguished from other tear proteins after SDS-PAGE. These findings indicate lacrimal secretion of free secretory component, even in the absence of its ligand. On the ocular surface, sIgM may play a compensatory role in IgA deficiency.

Adult↗

Cell-mediated immunity against human retinal extract, S-antigen, and interphotoreceptor retinoid binding protein in onchocercal chorioretinopathy.

Autoimmune mechanisms are thought to be involved in the pathogenesis of onchocercal chorioretinopathy. Cell-mediated immune responses to human retinal S-antigen, interphotoreceptor retinoid binding protein (IRBP), and crude retinal extract were investigated in patients with onchocerciasis from Sierra Leone, West Africa using a two-step migration-inhibition factor assay. Patients were subdivided into three groups: (1) without ocular involvement (n = 10), (2) with ocular onchocerciasis limited to the anterior segment (n = 19), and (3) with onchocercal chorioretinopathy (n = 21). A group of endemic controls (n = 25) from Sierra Leone were also studied. The cellular immune response to concanavalin A (Con A) was measured to assess the general capacity of lymphocytes to respond to a mitogen. Four of 50 (8%) patients with onchocerciasis and four of 25 (16%) endemic controls reacted with at least one retinal antigen. From the patients with onchocercal chorioretinopathy two of 21 (10%) showed a positive cellular response. The general mitogen response tested with Con A was positive in all these individuals. A role for an antiretinal autoimmune mechanism in the pathogenesis of onchocercal chorioretinopathy, as studied with human S-antigen, IRBP, or crude retinal extract, could not be shown because the cellular response to these antigens did not differ in patients with or without onchocercal chorioretinopathy or in endemic controls.

Adolescent↗

Analysis of aqueous humor immunoglobulin G in uveitis by enzyme-linked immunosorbent assay, isoelectric focusing, and immunoblotting.

Immunoglobulin G (IgG) in aqueous humor from patients with various uveitis syndromes was analyzed using a number of immunologic techniques. Sixty-five percent of patients with Fuchs' heterochromic cyclitis (FHC), 70% of patients with other forms of uveitis, and 44% of controls showed local synthesis of IgG, as demonstrated by an elevated IgG:albumin relative concentration ratio. Using an enzyme-linked immunosorbent assay to measure the concentration of IgG subclasses 1-4, a relative excess of IgG1 was found in the aqueous compared with the serum in FHC. Isoelectric focusing and immunoblotting studies revealed oligoclonal IgG bands in the aqueous of 13 of 23 (57%) patients with FHC, most being of the IgG1 subclass. Oligoclonal bands were not found in 18 patients with other types of uveitis or 13 patients undergoing surgery for senile cataract. These findings indicate intraocular production of IgG of restricted specificity in FHC, providing further evidence for local immune dysfunction in this condition. As yet the antigenic stimulus for this oligoclonal B-cell response has not been identified.

Adult↗

Selective binding of a 30-kilodalton protein to disposable hydrophilic contact lenses.

To investigate the accumulation of tear proteins on disposable extended-wear contact lenses (42% Etafilcon A and 58% hydration), a technique involving sodium dodecyl sulfate-polyacrylamide minigel electrophoresis combined with a sensitive silver-staining method was used. Besides the binding of large amounts of tear lysozyme the authors found an accumulation of an as yet unidentified 30-kilodalton (kD) protein. Longitudinal experiments showed lysozyme binding after 1 day of lens wear. The 30-kD protein was detected after a 2-day wearing period. The fact that protein deposition occurs during the relatively short wearing period of these lenses (1 week) may explain the unexpectedly high incidence of contact lens-associated conjunctivitis observed with these lenses.

Contact Lenses, Extended-Wear↗

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↗

Humoral autoimmune response against S-antigen and IRBP in ocular onchocerciasis.

Autoimmune mechanisms are thought to play a role in the pathogenesis of the chorioretinal changes in ocular onchocerciasis. In this study, the involvement of autoimmunity against retinal antigens in developing chorioretinitis was investigated. Serum levels of autoantibodies, directed against human S-antigen and interphotoreceptor retinoid-binding protein (IRBP), were determined in patients with onchocerciasis (n = 46) and endemic controls (n = 38) from Sierra Leone with the use of an enzyme immunoassay. In both groups high levels of anti-human S-antigen and IRBP antibodies were detected. No relationship could be demonstrated between the antiretinal antibody level and the occurrence of chorioretinitis in onchocerciasis. The levels of both anti-human S-antigen and IRBP antibodies were significantly higher in patients with onchocerciasis compared with endemic controls (P less than 0.001). Cross-reactivity of antiretinal antibodies with parasitic antigens could not be demonstrated as a possible explanation for the higher levels in patients with onchocerciasis. No correlation was found between the levels of antibodies of different classes against the crude Onchocerca volvulus, the egg antigen, or the microfilariae and the antiretinal antibody levels. Furthermore, in a panel of 13 different monoclonal antibodies directed against O. volvulus, only one showed a slight anti-human IRBP reactivity and none reacted with S-antigen. The immune response against the two retinal antigens investigated was not specific for onchocerciasis because high antibody levels were also found in patients with Bancroftian filariasis from Papua, New Guinea, and Surinam.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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↗

Diffusion of immunoglobulin G from the vascular compartment into the normal rabbit cornea.

In order to study the rate of entry of IgG into the normal cornea, IgG specific for human serum albumin was injected intravenously over a 2-month period into nonimmunized rabbits. The concentrations of total immunoglobulin G (IgG) and IgG specific for human serum albumin in serum, corneal tissue, and aqueous humor were determined with enzyme-linked immunosorbent assays. The experiments showed that the corneal concentration of IgG specific for human serum albumin increased by approximately 1% per day, whereas the total IgG concentration of the corneas used in this study was 70% of the concentration detected in serum. On the basis of these data it was hypothesized that an equilibrium between the serum and corneal IgG concentration was established after approximately 70 days. By injecting IgG preparations with different isoelectric point ranges, the influence of electrostatic interactions on the rate of entry into the cornea was investigated. It was found that charge had no effect on diffusion. From these results it was concluded that, after an antigenic stimulation, newly synthesized antibodies will be confined to the limbal region and will be noted only gradually at points nearer to the center. This indicates that the role of IgG during the immediate inflammatory response of the cornea is limited.

Animals↗

HPLC analysis of tear proteins in giant papillary conjunctivitis.

Giant papillary conjunctivitis (GPC) is a well defined entity seen in patients with deposits on their lenses. High performance liquid chromatography (HPLC) tear protein analysis was performed on 17 GPC patients and compared with healthy controls with and without contact lenses. The IgA levels are somewhat lower in GPC patients as compared with healthy controls not wearing lenses (P less than 0.05). A similar decrease was also seen in the control group wearing contact lenses. We were not able to identify a specific HPLC tear protein profile in GPC patients as compared with controls. The HPLC profile therefore gives no explanation for the lens deposits and is not suitable as a diagnostic or prognostic tool.

Adult↗

Risk factors for ocular sarcoidosis.

We reviewed 121 consecutive patients with biopsy-proven sarcoidosis who visited the sarcoidosis clinic of the University Hospital in Amsterdam, to determine the risk factors for the development of ocular manifestations. Of 121 patients 52 (43%) were black. Ocular disease developed in 50 (41%) patients and was more common in female and in black patients. uveitis was the most frequent manifestation of ocular sarcoidosis (29 out of 50 or 58%). There were no differences in the extra-ocular manifestations of the sarcoidosis between patients with and without ocular disease or between uveitis and non-uveitis patients. This study covered a mixed racial population and shows that different types of uveitis are seen in white and black patients. Anterior uveitis was more frequent in black patients (P less than .001), whereas posterior uveitis was more common in white patients (P less than .01). Chronic posterior uveitis with complications occurred most frequently in white female patients with late onset of the systemic disease. Uveitis was an early feature of sarcoidosis (25 out of 29 or 86%); moreover in 9 out of 29 (31%) cases, uveitis preceded the non-ocular detectable signs of sarcoidosis by more than one year. This emphasizes the importance of periodic re-evaluation of uveitis patients for sarcoidosis.

Adolescent↗

Secretory IgA and lysozyme in tears of patients with Graves' ophthalmopathy.

Using an enzyme linked immuno-assay (ELISA) and spectrophotometry, we determined levels of secretory IgA and lysozyme in tears of 69 patients with Graves' ophthalmopathy and 28 controls. The quantitative determination of secretory IgA and lysozyme in tears provided an impression of the functioning of the lacrimal gland in the two groups. An IgA/lysozyme ratio was calculated in both patients and controls as a parameter for the activity of the secretory IgA-producing plasma cells in the lacrimal gland. An increase in the IgA/lysozyme ratio was observed in 23 patients (33%) and one control (3%). Half of the patients who had suffered from the disease for more than 5 years showed a raised IgA/lysozyme ratio. No correlation was found between the IgA/lysozyme ratio and the NOSPECS classification. Our findings suggest that the lacrimal gland is involved in the orbital condition produced by Graves' ophthalmopathy. In most cases the involvement occurs in patients with a long history of the disease.

Adolescent↗

Circulating immune complexes in uveitis patients.

Immune complexes have been implicated in the pathogenesis of several types of uveitis. This has been substantiated in experimental models such as serum sickness, and in the analysis of the sera and aqueous of uveitis patients. The mechanisms influencing the deposition of the complexes in the eye are described. Furthermore a prospective study is presented, dealing with the presence of serum immune complexes and complement in 104 uveitis patients. A role for circulating immune complexes in the pathogenesis of uveitis could not be substantiated by this study.

Antigen-Antibody Complex↗