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Biomedical subjects

A Kijlstra

Publications and source records attributed to A Kijlstra.

At least 127 records · Page 7Linked to original sources
PubMed1992

Induction of autoantibodies to rat corneal protein 54.

Many studies have described the presence of circulating antibodies against corneal components in patients with corneal disease or uveitis, and in patients with skin or systemic disease with or without ocular involvement. The role of such antibodies in the underlying immunopathological process remains obscure. Here we describe the induction of autoantibodies against the rat cornea. Our attempts to induce corneal autoantibodies by various forms of keratitis and corneal trauma failed. However, circulating corneal autoantibodies could be detected by Western blotting after immunization of BN rats and Lewis rats with bovine corneal protein 54 (BCP 54). Rats immunized with rat corneal extracts (RaCE) or human serum albumin (HSA) as (auto) antigen did not develop corneal autoantibodies. During the study period (greater than 4 months), it was observed that the presence of circulating corneal autoantibodies did not elicit corneal inflammation. Severe keratitis did develop when BCP 54-immunized rats were challenged intracorneally with BCP 54, but the clinical signs were not significantly different from HSA-immunized rats after an intracorneal HSA challenge. Injection of corneal autoantibodies into the corneal stroma did not provoke keratitis. To the best of our knowledge this is the first study demonstrating corneal autoantibodies in rats without actual manipulation of the eye. This model may provide further insights in the role and significance of corneal autoantibodies in disease.

Aldehyde Dehydrogenase↗
PubMed1992

Uveitis and systemic disease.

A prospective study was conducted of 865 patients with uveitis to determine the frequency of associated systemic diseases and to assess the value of limited laboratory screening of these patients. All patients underwent a standard diagnostic protocol followed--when indicated--by special tests and procedures performed in order of likelihood ('tailored approach'). For 628 patients (73%) a specific diagnosis was established based on history, ophthalmologic examination, and laboratory and radiographic studies. A definite association with systemic disease was determined for 220 patients (26%). A relationship with a subclinical systemic disorder could be presumed in 201 cases (23%) and a well-established clinical uveitis entity without a recognisable systemic disorder was present in 207 cases (24%). For 237 patients (27%) a diagnosis could not be determined. The most frequently observed systemic diseases were sarcoidosis (7%) and HLA-B27-associated seronegative spondylarthropathies (6%). Presumed or definite toxoplasmosis was encountered in 10% of cases. HLA-B27-associated acute anterior uveitis was the most common clinical entity (17%). In the majority of cases the presence of a systemic disease was not suspected prior to eye involvement and was only recognised after the subsequent diagnostic procedures.

Adolescent↗
PubMed1992

Analysis of IL-6 levels in human vitreous fluid obtained from uveitis patients, patients with proliferative intraocular disorders and eye bank eyes.

Several studies suggest a role for IL-6 in the pathogenesis of uveitis. Earlier we have shown that aqueous humour obtained from patients with uveitis contained raised levels of IL-6. In the study described here we investigated the IL-6 levels in vitreous fluid samples obtained from 75 uveitis patients with different uveitis entities. Vitreous samples from 14 patients with proliferative intraocular disorders (PID) and 29 eye bank eyes were used as controls. All the samples were tested in the IL-6 B9 bioassay as well as in a sensitive ELISA for IL-6. Raised IL-6 levels were detected in the vitreous fluid of uveitis patients as well as patients with PID, implicating IL-6 as a common inflammatory mediator. The highest mean level of IL-6 was found in the vitreous fluid of patients with acute retinal necrosis. The mean IL-6 levels measured by the ELISA were higher compared to the levels measured by the B9 bioassay. This may be caused by the presence of B9 bioassay inhibitory factors in the vitreous fluid of these patients.

Biological Assay↗
PubMed1992

Anticardiolipin antibodies in uveitis.

Anticardiolipin antibodies (ACA) have been described in association with thrombosis and several vascular diseases and may be involved in retinal vasculitis. To investigate this question we tested sera from 86 patients with posterior uveitis and 100 healthy controls for the presence of anticardiolipin antibodies. The antibody was present in 15 patients: in 7 of the patients with acute retinal necrosis (n = 24), in 4 with idiopathic retinal vasculitis (n = 10), 3 with syphilis (n = 6) and in one SLE patient with retinal vasculitis. Ten patients had IgA-type anticardiolipin antibodies, 6 had IgM-type and 4 had IgG-type anticardiolipin antibodies. Anticardiolipin antibodies could not be detected in sera from uveitis patients with Behçet's disease (n = 10), sarcoid (n = 9), toxoplasmosis (n = 7), multiple sclerosis (n = 3) or Birdshot chorioretinopathy (n = 10). Ten of the healthy controls had cardiolipin antibodies of the IgM class. The exact role of these auto-antibodies in the pathogenesis of retinal vasculitis remains to be resolved.

Antibodies, Anticardiolipin↗
PubMed1992

Transient decrease of secretory IgA in tears during rigid gas permeable contact lens wear.

Decreased humoral defense mechanisms may be involved in the occurrence of keratic ulcerations after contact lens wear. To investigate the effect of contact lens wear on tear protein composition a prospective study was performed whereby tears were collected with Schirmer papers from 42 healthy individuals, before and at varying times after contact lens wear. Tear proteins were quantitated using HPLC analysis. Analysis of tear fluid by HPLC is a rapid and simple technique to detect the major tear proteins. Four separate peaks containing respectively IgA, lactoferrin, TSPA and lysozyme can easily be identified. The results show that the mean relative level of secretory IgA in the collected tear samples decreased significantly after the first months of contact lens wear but was not significantly altered after one year. The decrease in IgA was accompanied by a significant increase in the relative amount of lysozyme, whereas the levels of lactoferrin and TSPA remained the same. Certain individuals showed a marked decrease in their tear secretory IgA levels after wearing the lenses for more than one year. Future studies will clarify whether such individuals are at higher risk to develop corneal complications.

Adolescent↗
PubMed1992

Molecular weight forms of corneal aldehyde dehydrogenase.

Aldehyde dehydrogenase has recently been shown to be one of the major soluble proteins in the mammalian cornea. The enzyme has a subunit molecular weight of 54 kd and gel filtration experiments indicate that a dimer molecule is the enzymatically active species. The purpose of the studies described here was to investigate whether oligomeric forms of this enzyme could also be detected using the much faster SDS-PAGE mini-gel electrophoresis technique combined with immunoblotting and "in gel" enzyme detection. Low temperature treatment of samples prior to electrophoresis revealed that both human and bovine corneal ALDH are mainly present as a 54 kd and as a dimer molecule with an apparent molecular weight of 88 kd. Bovine corneal ALDH also contained larger oligomers with a molecular weight of 110, 154 and 210 kd respectively. The classical 3 minutes boiling procedure prior to SDS-PAGE dissociated the oligomers into the 54 kd subunit. Zymography experiments showed that enzyme activity was only present in the 88 kd form of corneal ALDH. Pretreatment of corneal ALDH at various temperatures showed that the temperature induced shift of the 88 kd species to the 54 kd subunit paralleled the decrease in enzymatic activity. The fact that reduction of samples with DTT did not dissociate the 88 kd form suggests that disulfide bridge formation is not involved in the oligomerisation of corneal ALDH.

Aldehyde Dehydrogenase↗
PubMed1992

Cytokines and uveitis, a review.

Although the exact pathogenic mechanisms underlying uveitis are unknown, cytokines appear to be involved in this inflammatory disorder. This review describes the studies in which the uveitogenic properties of several cytokines, including tumor necrosis factor (TNF), interleukin 1 (IL-1), IL-6, IL-8 and interferon gamma (IFN-gamma), were investigated and the reports on intraocular expression of cytokines, such as TNF, IL-2, IL-6 and IFN-gamma, during uveitis. The exact contribution of these mediators to uveitis remains to be determined. This may provide new clues in the treatment of uveitis.

Animals↗
PubMed1992

Polymorphism of the tumor necrosis factor region in relation to disease: an overview.

HLA antigens have been shown to be associated with several immunoinflammatory diseases. The mechanisms by which these antigens confer susceptibility to disease continue to be of major interest. Rapid progress has been made in the elucidation of the structure and function of class I and II MHC molecules, and several genes located within the HLA complex have been identified which are potentially involved in immunologic processes. Because of the HLA localization of the TNF-alpha and -beta genes and the biologic activities of the gene products, recent investigation has focused on a possible role of polymorphic TNF genes in the pathogenesis of HLA-associated diseases. Allelic variations have only been detected in the TNF-beta gene. No evidence has been found so far that a particular TNF-beta allele contributes significantly in the susceptibility to the diseases studied. Although it has been postulated that the TNF beta*2 allele contributes to susceptibility to IDDM in HLA-DR3, 4 heterozygous individuals, a larger group of HLA-typed patients and controls is needed to provide more conclusive evidence for this hypothesis. The increasing number of genes of unknown function encoded by the class III region leaves the possibility that the observed HLA associations in some diseases may be related to the presence of these genes. In AS, the lack of association with the TNF-beta alleles furthermore supports the function of the HLA-B27 molecule in the disease and underlines the improbability that HLA-B27 is merely a marker for a closely linked susceptibility gene.

Cytokines↗
PubMed1992

Endotoxin-induced uveitis in the rat. The significance of intraocular interleukin-6.

The potential role of interleukin-6 (IL-6) was studied as an inflammatory mediator of endotoxin (or lipopolysaccharide [LPS])-induced uveitis (EIU) in the rat. In young Lewis rats, levels of intraocular IL-6, but not serum IL-6, correlated with the severity of uveitis and with aqueous humor protein levels in response to foot pad injections of LPS (P less than 0.001). Adult Lewis rats did not develop uveitis and had no intraocular IL-6, although IL-6 was released systemically. Resistance to EIU and absence of IL-6 levels in the aqueous humor, despite the ability to release serum IL-6, also were observed in brown Norway rats, irrespective of age and weight. Intravitreal injection of as little as 1 ng of human recombinant IL-6 induced uveitis in young Lewis rats. In adult Lewis rats, and in young animals made tolerant to LPS, intravitreal IL-6 still caused substantial leakage of plasma proteins into the anterior chamber but no influx of inflammatory cells. As early as 2 hr after intravitreal injection of IL-6, immunohistochemical analysis showed invasion of the iris, corneal stroma, and anterior chamber by polymorphonuclear leukocytes (PMN) and expression of major histocompatibility complex (MHC) class II antigen in the retina by large cells that were macrophage-marker ED2 negative. This was followed by massive PMN infiltration of the retinal layers and vitreous. The MHC class II antigen expression of ciliary and iris epithelium occurred at a later stage (greater than 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effects of complement depletion on corneal inflammation in rats.

There are indications that complement activation may be involved in inflammatory processes of the cornea. To investigate the role of the complement system in experimental keratitis, rats were depleted of their plasma complement by treatment with cobra venom factor (CVF). intraperitoneal injection of CVF resulted in undetectable complement serum activity for 6 days when measured by a hemolytic assay. The corneal inflammatory response, induced by a single intracorneal injection of heterologous serum into nonsensitized CVF-treated rats, was suppressed significantly. The onset of the clinical symptoms of keratitis was delayed, and the severity was reduced. In addition, analysis of the serum antibody titers showed impaired antibody synthesis in the CVF-treated group. When keratitis was induced by an intracorneal antigen challenge in sensitized rats, no difference was observed when comparing the clinical signs of keratitis of CVF-treated animals with sham-treated animals. In addition, CVF treatment did not alter the course of lipopolysaccharide (LPS)-induced corneal inflammation. These findings suggest that the role of plasma complement activation in antigen- and LPS-induced keratitis appears to be limited. The implications for the immunopathologic mechanisms underlying keratitis are discussed.

Animals↗
PubMed1991

Analysis of local antibody production in the vitreous humor of patients with severe uveitis.

We analyzed the local antibody production in vitreous humor samples collected during vitrectomy in patients with severe vision-threatening uveitis. In 24 patients, paired serum and undiluted vitreous humor samples were collected and tested for antibodies against Toxoplasma gondii, herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and Toxocara canis. Total IgG and the Goldmann-Witmer coefficient were determined. The initial diagnosis of ocular toxoplasmosis could be confirmed in six of the seven patients. The seventh patient showed a local antibody production against herpes simplex virus. One of the three patients with chronic panuveitis at initial diagnosis showed a local antibody production against T. gondii. These last two findings resulted in a change in medical treatment. Analysis of local antibody production in vitreous humor samples is a valuable diagnostic tool.

Animals↗
PubMed1991

Restriction fragment length polymorphism of the tumor necrosis factor region in patients with ankylosing spondylitis.

Although ankylosing spondylitis (AS) is known to be strongly associated with the class I major histocompatibility complex antigen HLA-B27, B27 is probably not the only genetic factor involved in the pathogenesis of AS. Because of the involvement of tumor necrosis factor (TNF) in cartilage damage and the localization of the TNF genes in the proximity of the HLA-B locus, we investigated the association between AS and TNF alleles. The frequencies of the restriction fragment length polymorphisms linked to the TNF genes were determined in 73 AS patients and 81 controls. No differences were observed between AS patients and controls with respect to the frequencies of the TNF restriction fragment length polymorphisms.

Alleles↗
PubMed1991

Sjögren syndrome: comparative studies in local ocular and serum immunoglobulin concentrations with special reference to secretory IgA.

The objective of the present study was to examine Secretory IgA in tears and serum of Sjögren patients (34 patients and 23 controls). The test was performed in a parallel study using a polyclonal and a monoclonal method (Inter-Assay variation 9.1/Intra-Assay variation 5.5). No differences in the levels of tear secretory IgA were found between patients and controls. In serum however, secretory IgA, total IgA, IgM and IgG showed a significant increase in the Sjögren patients. The fact that secretory IgA levels remain normal in the ocular mucosa of these patients may explain that, despite the autoimmune destruction of the lacrimal gland, humoral defense factors are normally present on the surface of the eye to combat infections.

Antibodies, Monoclonal↗
PubMed1991

Clinical analysis of Fuchs' heterochromic cyclitis.

Fuchs' heterochromic cyclitis (FHC) is an important diagnosis to make. Not only for the patient, because incorrect diagnosis may lead to unnecessary therapy and the failure to detect secondary glaucoma, but also for the comparison of studies on the etiology of FHC, which is still unknown. No clinical criteria for establishing the diagnosis of FHC have been internationally accepted yet. By means of clinical analyses of FHC patients in different parts of the world, predominant clinical features may be distinguished and combined to form (internationally accepted) diagnostic criteria. We report a clinical analysis of 51 FHC patients in the Netherlands. Acute symptoms (severe redness, pain or photophobia) were never (100%) encountered. Characteristic keratic precipitates (88%) and/or minimal aqueous cells and flare (60%) and/or vitreous opacities (84%) were major signs, indicating a chronic inflammatory activity, in which no synechiae (100%) were present. Heterochromia (82%) was not a constant sign, but iris stromal atrophy, which causes the heterochromia, was always present (100%). Cataract was present in 82% as a result of the chronic iridocyclitis. Secondary glaucoma was present in 22%. Based on the predominant clinical findings obtained from this analysis of FHC patients, and on data in the literature, we propose clinical diagnostic criteria for FHC. Future studies, also including other uveitis groups, are necessary to confirm these diagnostic criteria.

Adolescent↗
PubMed1991

Elimination of immune precipitates from the rat corneal stroma: a histological study.

The pathogenesis of peripheral corneal lesions of immune aetiology, like Mooren's ulcer and catarrhal infiltrates, has been related to the formation or deposition of immune compkexes. The present investigation was undertaken to study the mechanisms involved in the elimination of immune precipitates from the cornea. Immune precipitates were induced by injecting human serum albumin (HSA) and rabbit anti-HSA serum into opposite sites of the rat corneal stroma. This resulted in a line-shaped opacity in the stroma, which remained visible by slit-lamp for 7 days, and disappeared without clinical signs of keratitis and uveitis. At the ultrastructural level, the immune precipitates were clearly visible. Keratocytes in the vicinity of the immune precipitates appeared activated, as suggested by their less flattened appearance and well-developed rough endoplasmic reticulum. The arrangement of the collagen fibrils was not affected. Cells with a macrophage-like morphology were also present and contained electron-dense material, closely resembling the precipitate, suggesting phagocytosis. Separate corneas were injected with latex beads, which is known to induce migration of Langerhans cells into the cornea. Immunohistochemical analysis revealed that both latex beads and immune precipitates induced migration of macrophages (ED1+) into the rat corneal stroma. However, differences were observed with regard to the expression of MHC class II antigens by these ED1+ cells and the presence of complement deposits in the corneal stroma. ED1+ cells in corneas injected with latex beads were all MHC class II positive (OX4+), whereas most of the ED1+ cells at the site of the immune precipitates were negative (OX4-).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Analysis of aqueous humour in ocular onchocerciasis.

The development of an onchocercal chorioretinopathy from the first detectable signs to a full blown oncho fundus is not fully understood. We investigated the intraocular humoral immune response against Onchocerca volvulus, human S-antigen, IRBP and crude retinal extract (using an ELISA) by examining paired aqueous humour and serum samples obtained from onchocerciasis patients (without [n = 10] and with ocular symptoms [n = 8]) and endemic controls [n = 14] from Sierra Leone (West Africa). A local intraocular anti-retinal IgG antibody production could not be demonstrated in onchocerciasis patients, whether they had ocular symptoms or not. A significantly higher level of O. volvulus antibodies and IgG was measured in the aqueous of onchocerciasis patients with ocular involvement, as compared to patients without ocular symptoms (Mann-Whitney ranksum test; p less than 0.001 and p less than 0.02 respectively). Since interleukin-6 (IL-6) plays an essential role in the differentiation of B cells into immunoglobulin producing plasma cells, we therefore measured this cytokine in paired aqueous and serum samples. Elevated IL-6 levels were found in the aqueous of two out of eight onchocerciasis patients tested. In view of these findings it seems improbable that retinal autoimmunity is a major factor in the pathogenesis of onchocercal chorioretinopathy. The high intraocular levels of antibodies against the parasite suggest a direct involvement of the parasite in the pathogenesis of onchocercal chorioretinopathy.

Adult↗