Comparison of clinical characteristics in patients with Vogt-Koyanagi-Harada disease with and without anti-retinal antibodies.

PURPOSE: To compare the clinical characteristics of Vogt-Koyanagi-Harada (VKH) disease patients with and without anti-retinal antibodies (ARAs) that are frequently detected in autoimmune retinopathy. METHODS: Using immunoblot analyses, serum autoantibodies for recoverin, carbonic anhydrase II, and α-enolase were examined in 20 treatment-naïve patients with VKH disease. Clinical factors before and after systemic corticosteroid therapy, including best-corrected visual acuity (BCVA) and macular outer retinal morphology, were statistically compared between patients with VKH disease with and without ARAs. RESULTS: Serum ARAs were detected in 50.0% of patients with VKH disease. There were no significant differences in clinical factors between the two groups, including final BCVA, frequency of uveitis recurrence, and recovery of the macular ellipsoid zone after systemic corticosteroid therapy. CONCLUSIONS: Our results suggest that the detected ARAs did not influence visual outcomes, the chronicity of uveitis, or outer retinal morphology in patients with VKH disease.

Detection of serum anti-retinal antibodies in the Chinese patients with presumed autoimmune retinopathy.

PURPOSE: To explore the presence of serum anti-retinal antibodies (ARAs) in the Chinese patients with presumed autoimmune retinopathy (AIR). METHODS: Twenty-three Chinese patients with presumed AIR, disease controls including 40 RP patients, 22 bilateral uveitis patients, 18 acute zonal outer occult retinopathy (AZOOR) patients, and 30 healthy donors were included. Serum samples of all the subjects were obtained and analyzed for the presence of four ARAs including recoverin, α-enolase, carbonic anhydraseII (CAII), and collapsin response-mediated protein (CRMP)-5 by Western bolt assay. RESULTS: ARAs were present in the serum of either presumed AIR patients, disease control, or healthy donors. One or more ARAs were present in the 78.2% of presumed AIR while they were indicated in the 35.0% of RP patients (p < 0.01) and 33.3% of healthy donors (p < 0.01). The prevalence of ARAs in the bilateral uveitis and AZOOR was 63.3% and 100% respectively. Positive rate of α-enolase antibody present in the presumed AIR, disease control, and healthy donors was 73.9%, 47.5%, and 33.3% respectively. Positive rate of CAII antibody present above groups was 52.1%, 50%, and 33.3% respectively. Recoverin antibody seemed to be specifically present in the serum of patients with cancer-associated retinopathy. CONCLUSION: Presence of serum ARAs including recoverin, α-enolase, CAII, or CRMP-5 in the Chinese patients with presumed AIR occurred significantly more often than RP patients and healthy donors. Seropositivity of ARAs had diagnostic value for the presumed AIR but mere presence was not sufficient for the diagnosis due to identification of them in the healthy controls and other retinal diseases.

[Aberrant expression of arrestin-1 and recoverin in kidney tumors].

INTRODUCTION: Early diagnosis of renal cell carcinoma (RCC) is extremely difficult, due to the late development of clinical manifestations. The study of the aberrant expression of tumor-associated antigens and a production of autoantibodies to these proteins seems promising and novel method for RCC diagnosis. AIM: To evaluate the possibility of using arrestin-1 (Arr-1), recoverin (Rec) and autoantibodies against arrestin-1 (AAA1) and recoverin (AAR) as a kidney tumor biomarker. MATERIALS AND METHODS: Primary kidney tumors and metastases of 62 patients were investigated. For immunohistochemical studies, tissues were incubated with polyclonal antibodies against Rec and Arr1 as the main antibodies. Detection of AAR and AAA-1 in the serum of patients was performed using Western Blot analysis according to a standard protocol. RESULTS: Among 62 tumors, renal cell carcinoma (RCC) constitutes 50 cases (86.4%), and oncocytoma was diagnosed in 12 patients (19.4%). In 11 (22%) cases of RCC, distant metastases were detected. Positive expression of Rec was observed in almost 71% of all types of kidney tumors. In 61.3% of patients with RCC, Arr-1 expression was seen. In the serum, AAR was found only in 1 patient (1.6%) with RCC. However, unlike AAR, AAA-1 in the serum of patients was observed much more often (75.8%). CONCLUSION: According to our data, the presence of AAA1 in the serum, unlike AAR, can be considered as an early kidney tumor biomarker. The high expression of recoverin and arrestin-1 in kidney tumors suggests the use of these proteins in future as a marker for the diagnosis or even as a potential target for immunotherapy.

Serum anti-recoverin antibodies is found in elderly patients with retinitis pigmentosa and cancer.

PURPOSE: To screen for anti-recoverin antibodies in elderly patients with retinitis pigmentosa (RP) with or without cancer and cross-sectionally characterize the seropositive patients clinically. METHODS: Serum from 75 RP patients who had been tested for mutations in a panel of 83 RP genes and 73 normal controls, all aged 50-80 years, were screened for anti-recoverin antibodies by Western blot using recombinant recoverin, retinal lysate from a marmoset and commercial anti-recoverin antibodies as a control. RESULTS: Three RP patients with typical pigmentary degeneration of the 75 (4.0%) were seropositive for anti-recoverin antibody. Pathogenic mutations were identified in two seropositive RP patients. All three patients had visual impairment since childhood and were diagnosed as RP by the age of 30. The severity of the retinopathy varied greatly among these three patients, ranging in visual acuity from light perception OU to 20/30 OU. Retinitis pigmentosa (RP) patients with a history of cancer were more likely to have anti-recoverin antibodies (3/14; 21.4%) than those without (0/61; 0%; p = 0.005, Fischer exact test). All 73 healthy controls with no history of cancer were also seronegative. CONCLUSION: Our results show that serum anti-recoverin antibodies can be detected in typical RP patients with identified pathogenic mutations and that a history of cancer may increase the risk of developing anti-recoverin antibodies.

A prospective, blinded analysis of A-PROTEIN (recoverin or CAR protein) levels in pediatric patients with central nervous system tumors.

BACKGROUND: Abnormal expression of A-PROTEIN has been identified in a number of tumors including carcinoma of the lung, breast, colon, prostate, and cervix. Brain tumors have been reported to express high plasma levels of A-PROTEIN, suggesting that it may be of significant diagnostic and prognostic value. PROCEDURE: This prospective study evaluated the sensitivity and specificity of A-PROTEIN levels in pediatric brain tumor patients. Patients included those with newly diagnosed disease pre- and post-surgery, during treatment, during routine follow-up, and at recurrence or progression. A total of 154 A-PROTEIN levels from 54 patients were evaluated. RESULTS: For patients without evidence of disease, 42% had normal A-PROTEIN levels, 35% were elevated, and 23% were equivocal. For patients with stable disease, 53% demonstrated normal A-PROTEIN levels, 19% were elevated, and 28% were equivocal. For patients with progressive disease, 53% had normal A-PROTEIN levels, 35% were elevated, and 12% were equivocal. The sensitivity was 35% and the specificity was 50%. A correlation of increased A-PROTEIN levels in patients with increased disease in glial tumors was also identified. CONCLUSIONS: A-PROTEIN levels were not predictive of disease status in children with most brain tumors. However, in patients with glial tumors there was a correlation with increased disease and elevated A-PROTEIN levels. This could represent variability of A-PROTEIN during growth, development, or tumor cell origin and needs further evaluation.

Cerebrospinal fluid (vascular endothelial growth factor) and serologic (recoverin) tumor markers for malignant glioma.

BACKGROUND: Clinically useful tumor markers have yet to be identified for malignant glioma. We report on two potential novel tumor markers, vascular endothelial growth factor (VEGF) and recoverin (protein A). VEGF is a highly specific endothelial cell activator that induces angiogenesis both in vivo and in vitro. Our study was designed to assess whether VEGF could be measured in the cerebrospinal fluid (CSF) of patients with cerebral neoplasms and used as a marker of particular tumors. We also studied serum recoverin levels in patients with various brain tumors and compared these to controls. Recoverin is a detectable serologic protein that is expressed in patients with cancer-associated retinopathy, a paraneoplastic syndrome. METHODS: In the VEGF arm, we used a solid-phase ELISA to determine the levels of VEGF. CSF samples from patients with anaplastic astrocytoma and glioblastoma multiforme (GBM) and with metastatic and nonastrocytic brain tumors were compared with nontumor control samples. In our recoverin study, an immunoenzymetric assay was used to measure the serum recoverin levels patients with glioma and compared with controls. RESULTS: In the VEGF arm, 89% of samples with malignant astrocytoma and 27% of nonastrocytoma samples had detectable levels of VEGF. VEGF was not detectable in normal CSF samples. The levels of VEGF were significantly higher in high-grade astrocytomas than in nonastrocytic tumors. Recoverin levels were 10-fold higher in patients with recurrent GBM relative to controls. In patients with low-grade glioma, anaplastic glioma, and GBM with no evidence of recurrence, a 3- to 5-fold increase was observed. CONCLUSIONS: VEGF is detectable in CSF and may be a potential marker for differentiating astrocytic from nonastrocytic tumors. Recoverin is detectable in serum and may be a useful glioma tumor marker, especially for recurrent active disease. These markers may have application for tumor diagnosis, surveillance, and treatment response.