Albuminuria and hypertension are independently associated with circulating antipericyte autoantibodies in type 2 diabetic patients.

AIMS: To determine whether albuminuria, hypertension, or HbA 1c are independently associated with antipericyte autoantibodies (APAAs) in type 2 diabetes mellitus. METHODS: Two hundred ninety-nine subjects with different degrees of retinopathy according to the Early Treatment Diabetic Retinopathy Study Scale participated in this study. Albuminuria was defined as an albumin/creatinine ratio above the normal cutoff limit, that is, 2.0 g/mol for men and 2.8 g/mol for women. Hypertension was defined as a diastolic blood pressure more than 90 mm Hg, a systolic blood pressure more than 140 mm Hg, or pharmacological antihypertensive treatment. Serum APAAs were detected by immunofluorescence on tissue-cultured bovine retinal pericytes. Association analysis was performed using univariate and multivariate statistical tools. RESULTS: In type 2 diabetes, APAAs were independently associated with albuminuria (OR = 0.56; P < .04), hypertension (OR = 2.21; P < .01), as well as with proliferative retinopathy (OR = 0.39; P < .01). CONCLUSIONS: The increased prevalence of APAA in patients with hypertension may suggest that these antibodies are related to tissue damage and repair and that the decline in frequency with albuminuria may serve as a marker for more advanced angiopathy. Future longitudinal studies are needed to determine whether the frequency of APAA is associated with the progression of angiopathy, and to determine the biological activity and antigens recognized by the antibody.

Monoclonal antibody (3G5)-defined ganglioside: cell surface marker of corneal keratocytes.

PURPOSE: To evaluate the anti-ganglioside monoclonal antibody 3G5 as a marker of corneal keratocytes. METHODS: 3G5 expression on keratocytes was investigated by immunofluorescence microscopy. Studies were performed on frozen sections of normal human, bovine, porcine, rabbit, rat, and mouse corneas and on repairing rabbit cornea. In vitro studies were performed on tissue-cultured human, bovine, porcine, mouse, and rabbit keratocytes. RESULTS: 3G5 stained frozen sections of human, bovine, porcine, rat, and rabbit cornea but not mouse cornea and the staining pattern followed the distribution of stromal keratocytes but did not stain epithelium or endothelium. Subconfluent human and bovine keratocyte cultures were 3G5 negative. Almost 100% of the human and bovine cells that were maintained at confluence without replacement of serum-containing culture medium for 2 weeks became 3G5 positive. The 3G5 antigen was constitutively expressed on cultured rabbit and porcine keratocytes under all conditions examined. Mouse keratocyte cultures did not express 3G5. The 3G5 antigen was not present on myofibroblastic cells in the repairing area of a full-thickness wound in rabbit cornea that had been healing for 20 days. The area surrounding the healing wound expressed 3G5 antigen in an altered distribution, whereas 3G5 antigen was distributed in the expected pattern in areas that were distant from the wound. When rabbit keratocytes were induced to express the myofibroblast marker alpha-smooth muscle actin by treatment with TGFbeta1 in vitro, the pattern of 3G5 staining was altered. CONCLUSIONS: The 3G5 antigen is a useful marker for the identification of corneal keratocytes and for documenting their response to environmental stimuli associated with wound repair.

Circulating antipericyte autoantibodies: a novel modifier of risk of progression of diabetic retinopathy?

BACKGROUND: Antipericyte autoantibodies (APAAs) are present in high frequency among diabetic subjects with and without nonproliferative retinopathy. This study aimed to determine whether progression of retinopathy in type 2 diabetes was associated with the same medical risk factors in APAA-positive subjects as in APAA-negative subjects. METHODS: Type 2 diabetic patients with nonproliferative diabetic retinopathy at baseline were followed prospectively for 2 years monitoring progression of retinopathy. Thirty-eight (21.7%) of 175 patients had progression in Early Treatment Diabetic Retinopathy Study grade by > or =2 steps in at least 1 eye. Serum APAAs were detected by immunofluorescence on tissue-cultured bovine retinal pericytes. RESULTS: Progression of retinopathy was associated with HbA(1c) level (P = 0.002), diabetes duration (P = 0.03), and albumin/creatinine ratio (P = 0.02) in APAA-negative subjects but not in APAA-positive subjects. The association between progression and APAAs was strongest in the upper quartile for HbA(1c) level (>8.0%), where 71.4% of patients negative for APAAs had progression of retinopathy while only 24.1% of patients positive for APAAs had progression (P = 0.007). CONCLUSION: The results suggest that APAA presence is a modifier of risk of progression of retinopathy due to hyperglycemia and that it could be useful as a biochemical marker of risk of progression of diabetic retinopathy in type 2 diabetic patients with poor metabolic control.