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Biomedical subjects

A Rothova

Publications and source records attributed to A Rothova.

At least 91 records · Page 5Linked to original sources

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↗

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↗

Side-effects of ivermectin in treatment of onchocerciasis.

In a prospective study to determine the tolerance for and safety of ivermectin therapy for onchocerciasis in a hyperendemic area in Sierra Leone, 28 (32%) of 87 patients had adverse reactions that required treatment with acetylsalicylic acid and antihistamines, but none of the observed adverse reactions were considered life-threatening. A significant relation was found between the frequency and severity of side-effects and the degree of parasite infestation, as quantified by the skin-snip counts. Free administration of ivermectin to severely infected onchocerciasis patients is not recommended without some form of medical supervision.

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↗

Aqueous humor analysis as a diagnostic tool in toxoplasma uveitis.

Analysis of local toxoplasma antibody production to confirm a suspected clinical diagnosis of toxoplasma chorioretinitis is a valuable diagnostic tool. Determination of toxoplasma antibodies in the blood of the patient is of limited use. When blood toxoplasma tests are negative this indicates that toxoplasma as a causative organisms in the pathogenesis of uveitis is unlikely. A positive blood test is a sensitive test (100% patients positive) but not a specific test since so many healthy individuals already have undergone subclinical infection and have acquired humoral immunity against the parasite. We analysed 93 paired aqueous and serum samples for toxoplasma antibodies and total IgG and determined the Goldmann-Wittmer coefficient. In patients retrospectively diagnosed as having toxoplasma chorioretinitis 16 out of 22 had a positive coefficient, indicating local parasite antibody production. In one patient with AIDS we also found a positive toxoplasma coefficient. Three out of 15 patients with posterior uveitis of unknown origin also had a positive coefficient. None of the cataract patients tested (n = 32) had a positive coefficient. Major drawbacks of aqueous humor analysis are that a false negative antibody coefficient can occur when a massive blood aqueous barrier breakdown has occurred.

Antibodies, Protozoan↗

Therapy of ocular toxoplasmosis.

We performed a prospective multicentre study to evaluate the efficacy of therapeutic strategies currently used for ocular toxoplasmosis in a large number of patients (n = 106). Treatment was given for at least four weeks and consisted of three triple drug combinations: group 1, pyrimethamine, sulphadiazine and corticosteroids (n = 29); group 2. clindamycin, sulphadiazine and corticosteroids (n = 37); and group 3. cotrimoxazole (trimethoprim and sulphamethoxazole) and corticosteroids (n = 8). Patients with peripheral retinal lesions remained without systemic therapy (group 4, n = 32). Patients from group 1 received leucovorin 5 mg twice a week. No difference in the duration of inflammatory activity was observed between the treated and untreated patients or between the separate groups of patients. The most important factor predicting the duration of inflammatory activity was the size of the retinal focus itself, independently of the therapy given (P less than 0.05). We showed a reduction in size of the retinal inflammatory focus in 52% of the pyrimethamine patients as compared to 25% of untreated cases. However the most frequent side effects were also associated with pyrimethamine medication and included hematologic complications as thrombocytopenia and leucopenia despite leucovorin medication.

Chorioretinitis↗

Antibodies against ocular and oral antigens in Behçet's disease associated with uveitis.

An indirect immunofluorescence test (IIF) using guinea pig lip as a substrate was performed with sera from 10 patients with Behçet's disease and the results were compared to IIF with sera of 16 patients with uveitis of Turkish origin, 62 patients with non- Behçet's uveitis, 9 patients with stomatitis aphtosa and 34 healthy controls. Antibodies to guinea pig lip cytoplasmic antigens were present in 70% of the Behçet patients, in 19% of uveitis patients of Turkish origin (P less than 0.05), in 12% of the non Behçet uveitis patients (P less than 0.001), in 11% of the stomatitis aphtosa patients (P less than 0.05) and in 9% of the healthy controls (P less than 0.001). A positive Behçet serum preincubated with the supernatant of guinea pig lip sections incubated in PBS gave an inhibition on the IIF test, indicating that the antigen involved in a soluble cytoplasmic substance. No significant increase in the presence of antibodies against iris, cornea or retina (mouse eye) were detected in the Behçet sera. Of interest was the finding of a positive reaction in 6 out of 10 patients in the episcleral region of the mouse eye. This positive reaction resembles immune complex like material. Our findings suggest that using the external surface of the guinea pig lip as a substrate is useful in selecting out those patients with Behçet's disease from uveitis patients with an unknown etiology and from patients with aphtous stomatitis.

Adult↗

Immunity to a corneal antigen in Fuchs' heterochromic cyclitis patients.

Immunity to a major corneal antigen was studied in 28 Fuchs' heterochromic cyclitis patients and compared with the response of 44 patients with other types of uveitis and 19 healthy controls. The highest incidence of immune response was found in patients with anterior segment involvement only (anterior uveitis and Fuchs') whereas the frequency of anti-corneal immune response in patients with posterior segment involvement only was low and not significantly different from that of healthy controls. Cellular immunity to corneal antigens was found in the majority of Fuchs' heterochromic cyclitis patients, and in one-third of the anterior uveitis patients. No correlation could be established in these patients between a positive cellular response and the chronicity of the disease or the presence of keratic precipitates. Humoral immunity to the corneal antigen was also the highest in patients with anterior segment involvement, but there was no difference in response between Fuchs' and non-Fuchs' anterior uveitis patients. This study suggests that anti-corneal immunity may be triggered in inflammatory diseases of the anterior segment, especially in Fuchs' heterochromic cyclitis.

Adult↗

Uveitis and diabetes mellitus.

Of 340 patients with anterior uveitis, 20 (6%) had diabetes mellitus. This is significantly higher than the prevalence of 1.4% in the normal Dutch population (P less than .001). Of 128 patients with idiopathic anterior uveitis, 16 (12.5%) had diabetes mellitus compared to only four (1.9%) of 212 patients with anterior uveitis with an established specific ocular diagnosis (P less than .001). Of the 16 diabetic patients with idiopathic anterior uveitis, ten (63%) had type I diabetes mellitus and 12 (75%) suffered from severe diabetic complications as angiopathy, nephropathy, and neuropathy. The onset of diabetes mellitus preceded the onset of anterior uveitis in all cases. Whether or not uveitis in diabetic patients is a true inflammation rather than an ischemic phenomenon is still unknown.

Diabetes Complications↗

High incidence of corneal epithelium antibodies in Fuch's heterochromic cyclitis.

Sera obtained from 26 patients with Fuchs' heterochromic cyclitis were examined for the presence of autoantibodies directed against the anterior segment of the eye by means of immunofluorescence techniques. Antibodies against human iris tissue could not be detected, whereas autoantibodies against corneal epithelium were found in almost 90% of cases. This is the first report describing the presence of autoantibodies in patients with Fuchs' heterochromic cyclitis and it provides a further clue that immunological mechanisms might play an important role in the aetiology of Fuchs' heterochromic cyclitis.

Adult↗

Clinical features of acute anterior uveitis.

We studied the clinical features and prognosis of 73 patients with HLA-B27 positive and 71 patients with HLA-B27 negative acute anterior uveitis using computer analysis of more than 50 variables per patient. The patients with HLA-B27 positive acute anterior uveitis showed the following characteristics which were significantly different from patients with HLA-B27 negative acute anterior uveitis: younger age at onset; high male to female ratio; frequent unilateral alternating eye involvement; severe ocular symptoms during activity, such as presence of fibrin in the anterior chamber; absence of mutton fat keratic precipitates; high incidence of ocular complications; and frequent association with seronegative spondyloarthropathies. Despite the difference of disease severity and incidence of complications, the long-term visual outcome did not differ significantly between the two groups. No distinctions were observed when patients with HLA-B27 positive acute anterior uveitis were subdivided according to sex or the presence of ankylosing spondylitis. HLA-B27 positive acute anterior uveitis formed a distinct clinical entity associated with serious prognosis as compared to HLA-B27 negative acute anterior uveitis.

Acute Disease↗

Humoral and cellular immune responsiveness to human S-antigen in uveitis.

Purified human retinal S-antigen (S-ag) was used to investigate the occurrence of humoral and cellular autoimmune reactions against S-ag in uveitis patients. With a sensitive ELISA method anti-S-ag antibodies could be detected in the sera of 28% of the uveitis patients. No difference was found between patients with posterior or panuveitis (31 out of 117 positive) and patients with anterior or intermediate uveitis (16 out of 52 positive). Similar frequencies and levels of anti-S-ag autoantibodies were also found among healthy controls (6/20) and patients who had undergone cataract surgery (6/17). Immunoblotting with purified S-ag and with whole human retinal extract confirmed the presence of anti-S-ag antibodies in uveitis and control sera. Moreover, antibodies against various other retinal proteins could also be demonstrated in patients and controls, without being particularly enhanced in uveitis. The cellular immune responsiveness was tested by measuring the production of migration inhibitory factor (MIF) during overnight culture of peripheral mononuclear cells with the antigen. None of 18 healthy controls responded, whereas 17 positive reactions were observed in the group of 44 uveitis patients. The highest frequencies were found in patients with posterior (5/12) or pan- (7/12) uveitis, while of the responders with anterior (2/8) or intermediate (3/12) uveitis, three had disorders affecting the retina. Thus, cellular autoimmune responsiveness to S-ag is apparently associated with posterior and pan-uveitis, and might also occur in non-uveitic retinal disorders, whereas the occurrence of anti-S-ag antibodies is probably not at all pathognomic for uveitis.

Adolescent↗

Genes on chromosome 14q and their role in the pathogenesis of HLA-B27 associated diseases.

Genetic factors other than HLA-B27 may play a role in the pathogenesis of ankylosing spondylitis (AS), acute anterior uveitis (AAU) and Reiter's syndrome (RS). Studies by Brewerton et al. and Kijlstra et al. showed associations between the MZ phenotype of alpha 1-antitrypsin and the Gm phenotype zafngb of IgG in patients with AAU, who developed AS. The loci for alpha 1-antitrypsin (PI) and Gm allotypes (IGH) are situated on the tip of the long arm of chromosome 14. In the present study we tried to clarify and extend the above studies. In 41 B27+ AAU patients with AS the alpha 1-antitrypsin and Gm phenotype and allotype frequencies were not statistically different from those in B27+ AS patients developing AAU and in B27+ AAU patients without AS, in B27+ AS patients without AAU, B27+ patients with Reiter's syndrome, B27+ patients with low back pain, B27- AAU patients and normal controls. It is therefore unlikely that genes on the tip of chromosome 14 play a role in the pathogenesis of B27 associated diseases. A hypothesis was formed suggesting that a bacterial-derived modifying factor may replace the position of beta 2 microglobulin in the HLA-B27 molecule resulting in an impaired cytotoxic T cell reactivity.

Alleles↗

Aqueous chamber taps in toxoplasmic chorioretinitis.

The clinical value of the determination of toxoplasma antibodies in anterior chamber taps was evaluated in 12 posterior uveitis patients suspected of a toxoplasmic retinochoroiditis, in four patients with Fuchs's heterochromia and in 31 cataract patients. The posterior uveitis patients all had marked inflammation of the vitreous obstructing the examination of the fundus of the time of aqueous humour aspiration. The clinical diagnosis toxoplasmic uveitis (n = 9) was made after the inflammation of the vitreous had subsided and fundus examination became possible again. Paired serum and aqueous samples were tested for total immunoglobulin levels and toxoplasma antibodies. Eight of the nine clinical toxoplasmic uveitis patients had detectable toxoplasma antibodies in their aqueous, whereas none of the other seven uveitis patients were positive. All of these eight toxoplasmic uveitis patients had a coefficient above 1.5. Of the 31 control patients only one had a positive antibody titer at a dilution of 1/2 with a corresponding coefficient of 1.1. This study shows that aqueous humour examination for toxoplasma antibodies is a valuable diagnostic tool in a selected group of posterior uveitis patients.

Antibodies↗