Serum autoantibodies to alpha-fodrin are present in glaucoma patients from Germany and the United States.
OBJECTIVE
Glaucoma is characterized by a progressive loss of retinal ganglion cells that results in a characteristic optic neuropathy associated with visual field loss. In previous studies, changes in the antibody profiles have been shown in the sera of patients with glaucoma, and these findings suggest a role for autoimmune involvement in the pathogenesis of glaucoma in some patients. The purpose of this study was to compare the antibody profiles against optic nerve antigens in patients with glaucoma in two different study populations from Germany and the United States.


METHODS
One hundred twenty patients were included in the study, 60 from Germany and 60 from the United States: a control group (CTRL, n = 20), a group of patients with primary open-angle glaucoma (POAG, n = 20), and one group of patients with normal-pressure glaucoma (NPG, n = 20) from each country. Western blot analyses against bovine optic nerve antigens were used to detect the IgG antibody patterns present in the patients' sera. The complex antibody profiles were analyzed by multivariate statistical techniques.


RESULTS
Complex IgG autoantibody repertoires were present in all patients with glaucoma as well as healthy subjects from both the German and the United States study population. A large similarity between all antibody profiles in both study populations was demonstrated in the number and frequency of both up- and downregulation of antibody reactivities in patients with glaucoma of both national cohorts. The multivariate analysis of discriminance found a significant difference between the glaucoma groups and healthy subjects against optic nerve antigens. As in previous studies, the NPG group revealed the highest variance from the control group (P < 0.01). Furthermore, a newly described antibody biomarker in both study populations was identified as alpha-fodrin. Western blot results revealed that there was an increased frequency and enhanced immunoreactivity to alpha-fodrin (120 kDa) in the sera of patients with NPG. The presence of alpha-fodrin autoantibodies were confirmed by ELISA, in which a highly elevated anti-alpha-fodrin titer in patients with NPG was found to be significantly greater than in the control subjects (P < 0.01) or age-matched patients with POAG (P < 0.04).


CONCLUSIONS
Complex IgG antibody patterns against optic nerve antigens can be reproducibly identified in the serum of study populations from the United States and Germany. In both cohorts, patients with glaucoma have characteristic differences in serum autoantibody repertoires from those in control subjects. A newly described autoantibody to alpha-fodrin found in other neurodegenerative diseases such as Alzheimer's, further implicate a role for autoimmunity and the neurodegenerative processes in glaucoma. The high correspondence of the autoantibody patterns found in the study populations from different continents provides further evidence that serum autoantibody patterns may be useful biomarkers for glaucoma detection or for determining prognosis in future studies by means of pattern-matching algorithms.
Grus
Franz H
FH
Universitaets-Augenklinik, Department of Ophthalmology, Johannes Gutenberg-University, Mainz, Germany. grus@eye-research.org
Joachim
Stephanie C
SC
Bruns
Kai
K
Lackner
Karl J
KJ
Pfeiffer
Norbert
N
Wax
Martin B
MB
D000368:Aged; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000276:immunology*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005858:Germany; D005902:Glaucoma, Open-Angle / Q000276:immunology*; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008840:Microfilament Proteins / Q000276:immunology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000276:immunology*; D014481:United States; D013049:Spectrin
D001323:Autoantibodies; D001324:Autoantigens; D002352:Carrier Proteins; D005136:Eye Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D013049:Spectrin