B Cell Anomalies in Autoimmune Retinopathy (AIR).

Purpose: Autoimmune retinopathy (AIR) is a retinopathy associated with unexplained vision loss presumably linked to circulating antiretinal antibodies; currently, however, there are no standardized criteria regarding the diagnosis, treatment strategy, or pathogenesis of this disease. The importance of B-lymphocyte immunophenotyping in the classification of AIR is unknown. Methods: We utilized 15-color multiparametric flow cytometry to identify aberrations in B cell subsets that may contribute to the pathophysiology of AIR. Luminex cytokine analysis was also performed on plasma samples from AIR patients. Results: Significant differences in AIR patients compared to individuals with other inflammatory conditions or healthy donors were found in the B cell memory compartment, including an increase in naïve B cells and a decrease in switched and unswitched memory B cells, which correlated with alterations in immunoglobulin secretion. Conclusions: These findings suggest that the maturation process of B cells may be impaired and that B cell immunophenotyping may help in understanding disease process in AIR.

Evaluation of serum resistin levels in patients with ocular and non-ocular Behçet's disease.

BACKGROUND: Resistin, a recently identified adipocytokine, has been found to play an important role in inflammation and the processes of inflammation-related diseases. Serum resistin levels in patients with Behçet's disease (BD) have not yet been investigated. We aimed to evaluate the relation between resistin and interleukin-6 (IL-6) in Behçet patients with or without ocular involvement and in normal controls. METHODS: Twenty-two patients with BD and 19 healthy control subjects were included in this study. While 14 patients had posterior segment involvement of the eye, the other 8 did not have ocular disease. Serum resistin and interleukin-6 (IL-6), levels were measured in all samples. Data from all groups were tested for statistical significance. RESULTS: The mean resistin and IL-6 concentrations were significantly higher in patients with BD than the control subjects (p = 0.011 and p = 0.0001, respectively). There was a significant difference in resistin and IL-6 levels between the patients with non-ocular BD and controls (p = 0.013 and p = 0.0001, respectively), as well as resistin and IL-6 levels between the ocular BD group and the control group (p = 0.05 and p = 0.0001, respectively). However, there was no significant difference between patients with ocular versus non-ocular BD. INTERPRETATION: Resistin levels were found to be raised in Behçet patients with or without ocular involvement compared with the control subjects.

Serum cytokine levels in active uveitis and remission.

Serum levels of interleukin(IL)-8, IL-6, and (TNF)-alpha were measured in 25 patients during active uveitis and uveitis in remission and compared to age-matched controls. Levels of IL-8 and IL-6 were significantly elevated in patients with active disease and were decreased during remission. IL-8 levels were highest in patients with anterior uveitis, with greatest difference between active disease and remission. No consistent pattern was observed for TNF-alpha. In conclusion, serum cytokine levels are elevated in active noninfectious uveitis. The rise in IL-8 may suggest innate immune mechanisms in the acute disease, while IL-6 participates in modulation of inflammation in the chronic disease.

Humoral immune response directed against LEDGF in patients with VKH.

Vogt-Koyanagi-Harada disease is an autoimmune systemic disorder. In Vogt-Koyanagi-Harada disease, inflammatory disorders occur in multiple organs containing melanocytes, including uvea (resulting in acute bilateral panuveitis), skin (resulting in vitiligo and alopecia), central nervous system (resulting in meningitis) and inner ears (resulting in hearing loss and tinnitus). These inflammatory aspects are attributed to the destruction of melanocytes through immunological mechanisms. Studies have been carried out to elucidate the exact etiology and target autoantigen in Vogt-Koyanagi-Harada disease, but much remains to be investigated. Identification of target autoantigen is important to understand the etiology of autoimmune diseases, and for development of antigen-specific immuno-modulation therapy. To identify the target autoantigens in Vogt-Koyanagi-Harada disease, we made use of an immunoscreening of a bovine uveal cDNA expression library with serum samples obtained from patients with Vogt-Koyanagi-Harada disease. We identified an immunoreactive cDNA clone that encodes bovine lens epithelium derived growth factor. mRNA of human lens epithelium derived growth factor was determined by reverse transcription-polymerase chain reaction and it was expressed in human uvea, retina and melanocytes. Immunoglobulin G (IgG) autoantibodies were quantitated in an enzyme-linked immunosorbent assay, using recombinant human lens epithelium derived growth factor. The prevalence of IgG anti-lens epithelium derived growth factor autoantibodies in patients with Vogt-Koyanagi-Harada disease was significantly higher than that in healthy controls (66.7% versus 21.6%, P<0.001). On the other hand, the prevalence of the autoantibody in patients with panuveitis of other etiology, Behçet's disease and sarcoidosis, was almost same as that in healthy controls. These results suggest that the humoral immune response agonist lens epithelium derived growth factor is not a mere secondary phenomena caused by uveal tissue damage.

Cyclosporine therapy for severe sight-threatening uveitis in children and adolescents.

OBJECTIVE: To review the safety and efficacy of cyclosporine in the treatment of children with severe bilateral sight-threatening intermediate uveitis or panuveitis. DESIGN/PARTICIPANTS: A retrospective chart review was performed on all children younger than 18 years of age with chronic bilateral sight-threatening uveitis who were treated with cyclosporine. MAIN OUTCOME MEASURES: Assessment of the therapeutic efficacy and development of adverse effects of cyclosporine after 6 months, 2 years, and 4 years of therapy was performed. RESULTS: Between 1983 and 1992, 15 children and adolescents were treated with cyclosporine. After 6 months, visual acuity improved or stabilized in 82.1% of eyes, while median vitreous inflammation decreased from 2.0 to 0.5. After 2 and 4 years, visual acuity improved or stabilized in 64% and 75% of eyes, respectively. Median vitreous inflammation remained 0.5 after 2 and 4 years of therapy. Mean creatinine clearance and hemoglobin values decreased and serum creatinine increased after 6 months. After 2 years, only mean hemoglobin values remained decreased. After 4 years, no significant differences were noted in any of the laboratory studies. The most frequently noted side effects included transient increases in serum creatinine in 53%, gingival hyperplasia in 40%, and hirsutism in 20% of patients. CONCLUSIONS: The authors' results suggest that cyclosporine is a safe and effective therapy for the treatment of children with severe bilateral sight-threatening intermediate uveitis or panuveitis.

Identification, quantitation, and purification of a 36 kDa circulating protein associated with active pars planitis.

PURPOSE: To establish a correlation between the presence of a 36 kDa protein in the blood of patients with pars planitis and to characterize and purify this protein. METHODS: Blood samples were obtained from patients with pars planitis and other types of uveitis and from various controls. Samples were treated with polyethelene glycol and protein A and were analyzed on 10% SDS-PAGE for the presence of a 36 kDa protein. Quantitative estimation of the level of this protein was determined by densitometric tracing of the stained gels. Polyclonal antibodies were raised by immunizing New Zealand White rabbits with a mixture of the gel fragment containing the 36 kDa protein (p-36) and complete Freund's adjuvant. These antibodies were used in the immunoaffinity purification of this protein. RESULTS: The levels of p-36 were sixfold to eightfold higher in 81% of the patients with active pars planitis than in controls (P < 0.05). Furthermore, the levels of this protein correlated with disease activity. A partial amino terminal sequence analysis revealed that p-36 may be a novel protein. It has been purified from the patient's blood using affinity chromatography. CONCLUSIONS: A 36 kDa protein (p-36) is found in elevated concentrations in the blood of many patients with active pars planitis. Its putative role in the etiopathogenesis of pars planitis is unknown.

Anti-toxoplasma serotitres in uveitis and ocular toxoplasmosis.

This study was based on anti-toxoplasma serotitres obtained from 80 normal healthy adults and 103 consecutive patients with anterior, posterior and panuveitis over a 42 month period. Twelve out of 80 (15%) normal healthy sera were found to have low titres (1:64 to 1:256), while 3 (3.8%) had high titres (1:1024 or higher). The distribution of serotitres in patients with clinical toxoplasmosis was significantly different from the population sample (p less than 0.001, chi-squared test). Similarly, the distribution of serotitres in patients with posterior uveitis (of which 28 out of 54 were clinically ocular toxoplasmosis) having serotitres of 1:1024 or greater, was found to be significantly different from the normal population (p less than 0.001, Chi-squared test), but not statistically different from those with clinical ocular toxoplasmosis. Hence, anti-toxoplasma serotitre is useful as a diagnostic screening tool only in patients with posterior uveitis. It is also useful in confirming cases of suspected clinically positive ocular toxoplasmosis in our local population.