Stephanie C Joachim

Publications (17)42.37 Total impact

• Source

  Available from: Nils Boehm

  Article: Effect of ischemia duration on autoantibody response in rats undergoing retinal ischemia-reperfusion.

  Stephanie C Joachim, Thomas Jehle, Nils Boehm, Oliver W Gramlich, Wolf A Lagreze, Norbert Pfeiffer, Franz H Grus
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  ABSTRACT: Both the innate and the adaptive immune systems are involved in the pathogenic processes following ischemia-reperfusion injury. We analyzed the possible correlation between the duration of ischemia and autoantibody diversification in a model of ocular ischemia. Rats were subjected to 30, 45, or 90 min of ischemia, and retinal ganglion cell (RGC) density and antibody reactivity were analyzed via customized protein microarray slides. After ocular ischemia, significant alterations in antibody response were observed, while increasing exposure caused more severe RGC damage. Distinct antibody responses after ischemia were detected; these alterations comprised decreased reactivities against cyclophilin A and glyceraldehyde-3-phosphate dehydrogenase, possibly due to increased binding of circulating antibodies to debris material. Other antibodies, like those against α(5)β(1)-integrin or β(2) -adrenergic receptor, were upregulated after ischemia.
  Ophthalmic Research 03/2012; 48(2):67-74. · 1.56 Impact Factor
• Source

  Available from: PubMed Central

  Article: Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens.

  Stephanie C Joachim, Oliver W Gramlich, Panagiotis Laspas, Heiko Schmid, Sabine Beck, Harald D von Pein, H Burkhard Dick, Norbert Pfeiffer, Franz H Grus
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  ABSTRACT: Antibodies against retinal and optic nerve antigens are detectable in glaucoma patients. Recent studies using a model of experimental autoimmune glaucoma demonstrated that immunization with certain ocular antigens causes an immun-mediated retinal ganglion cell loss in rats. Rats immunized with a retinal ganglion cell layer homogenate (RGA) had a reduced retinal ganglion cell density on retinal flatmounts (p = 0.007) and a lower number of Brn3(+) retinal ganglion cells (p = 0.0001) after six weeks. The autoreactive antibody development against retina and optic nerve was examined throughout the study. The levels of autoreactive antibodies continuously increased up to 6 weeks (retina: p = 0.004; optic nerve: p = 0.000003). Additionally, antibody deposits were detected in the retina (p = 0.02). After 6 weeks a reactive gliosis (GFAP density: RGA: 174.7±41.9; CO: 137.6±36.8, p = 0.0006; %GFAP(+) area: RGA: 8.5±3.4; CO: 5.9±3.6, p = 0.006) as well as elevated level of Iba1(+) microglia cells (p = 0.003) was observed in retinas of RGA animals. Our findings suggest that these antibodies play a substantial role in mechanisms leading to retinal ganglion cell death. This seems to lead to glia cell activation as well as the invasion of microglia, which might be associated with debris clearance.
  PLoS ONE 01/2012; 7(7):e40616. · 4.09 Impact Factor
• Article: Ophthalmopathology in rats with MBP-induced experimental autoimmune encephalomyelitis.

  Oliver W Gramlich, Stephanie C Joachim, Philip F Gottschling, Panagoitis Laspas, Clemens S Cuny, Norbert Pfeiffer, Franz H Grus
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  ABSTRACT: Multiple studies indicate that T-cells play a major role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, but recently an involvement of antibodies has also been discussed. The aim of our study was to examine the effects of myelin basic protein (MBP) immunization on survival of neurons, alteration of antibody reactivity, and microglia in the retinal ganglion cell layer. EAE was induced in rats by immunization with MBP. Intraocular pressure (IOP) measurements and funduscopies were performed regularly. Neuron cell density was evaluated on cresyl-stained retinal flatmounts. IgG antibody deposition and activated microglia were detected in retina and optic nerve sections via immunohistology. The intensity of autoreactive IgG antibodies was quantified in successive serum samples via tissue arrays. Significant loss of neurons was detected 6 weeks after immunization (p < 0.05). At the same time, IgG antibody deposits accumulated in the retina and the optic nerve of EAE animals and a significant microglia turn-over to activation was observed. The level of IgG antibody reactivity against retina and optic nerve tissue continuously increased (p < 0.05). While clinical parameters indicated typical EAE progression, we observed no changes in IOP (p > 0.9) or abnormalities in fundi. Immunization with MBP not only causes neuron loss in the retinal ganglion cell layer, but also triggers antibody reactivity against ocular tissue. Possibly some of these antibodies are involved in the induction of neuronal apoptosis. This study suggests that, apart from T-cell mediation, alteration of antibody reactivity and activated microglia do also influence the ocular pathomechanisms in the EAE model.
  Albrecht von Graæes Archiv für Ophthalmologie 02/2011; 249(7):1009-20. · 2.17 Impact Factor
• Source

  Available from: Nils Boehm

  Article: Upregulation of antibody response to heat shock proteins and tissue antigens in an ocular ischemia model.

  Stephanie C Joachim, Martin B Wax, Nils Boehm, Desiree R Dirk, Norbert Pfeiffer, Franz H Grus
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  ABSTRACT: The aim of this study was to characterize the serum antibody reactivities occurring after ocular ischemia reperfusion. The time course of serum antibody responses was examined. Wistar rats were exposed to transient ocular ischemia by elevating intraocular pressure to 130 mm Hg for 60 minutes. Axonal damage was evaluated on optic-nerve sections 2 and 4 weeks later. Blood samples collected before and several times after ischemia were used for antibody detection via customized protein microarrays. Different tissue antigens, including heat shock proteins (HSPs) and crystallins, were selected based on previous identification of antibody reactivities in studies on ischemic events or ophthalmic diseases associated with ischemia. Antibody reactivity was compared using multivariate statistical techniques. Significant axonal damage was observed 2 and 4 weeks after ocular ischemia (P < 0.05). Animals showed certain immunoreactivities against antigens even before ischemia, whereas many reactivities increased afterward. Significantly different responses were detected 2, 3, and 4 weeks after ischemia (P < 0.05). Antibody reactivity against actin, glial fibrillary acidic protein, HSP 27, vimentin, or spectrin continually increased. Ischemia induced by acute intraocular pressure elevation led to complex changes in antibody reactivities in sera of treated animals. Upregulation of serum autoantibodies, especially against heat shock and structural proteins, progressively increased throughout the 4-week follow-up period, whereas others such as ubiquitin decreased. The upregulation of anti-HSP 27 antibodies might be an attempt to protect the tissue from ischemic damage.
  Investigative ophthalmology & visual science 02/2011; 52(6):3468-74. · 3.43 Impact Factor
• Article: Autoreactive antibodies and loss of retinal ganglion cells in rats induced by immunization with ocular antigens.

  Panagiotis Laspas, Oliver W Gramlich, Harald D Müller, Clemens S Cuny, Philip F Gottschling, Norbert Pfeiffer, H Burkhard Dick, Stephanie C Joachim, Franz H Grus
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  ABSTRACT: In an experimental autoimmune animal model, retinal ganglion cell (RGC) loss was induced through immunization with glaucoma-related antigens. The target of this study was to investigate the pathomechanism behind this decline and the serum antibody reactivity against ocular and neuronal tissues after immunization with glaucoma- and non-glaucoma-associated antigens. Rats immunized with optic nerve antigen homogenate (ONA) or keratin (KER) were compared to control rats (CO). Intraocular pressure (IOP) was measured, and the fundi were examined regularly. Four weeks afterward, cells were counted in retinal flat mounts. Retina, optic nerve, and brain sections from healthy animals and optic nerve sections from immunized animals were incubated with serum collected at different time points. The occurrence of autoreactive antibodies was examined. Signs of antibody deposits, microglia activation, and demyelination were sought in optic nerves of immunized animals. Brain sections were examined for abnormalities. No IOP or fundus changes were observed. Animals immunized with ONA showed a significant cell loss compared with the CO group. Elevated autoreactive antibodies against retina, optic nerve, and brain were observed. Animals immunized with KER, despite their immunologic response against KER, demonstrated neither RGC loss, nor increased development of autoreactive antibodies. Optic nerve from animals immunized with ONA demonstrated antibody accumulation, glia activation, and demyelination. No such observations were made in the KER or CO groups. Brain sections were without pathologic findings. Systemic autoimmunity against ocular and neuronal epitopes, mediated by accordant autoreactive antibodies, is involved in the inflammatory processes that cause RGC degeneration in this experimental animal model.
  Investigative ophthalmology & visual science 01/2011; 52(12):8835-48. · 3.43 Impact Factor
• Article: Complex antibody profile changes in an experimental autoimmune glaucoma animal model.

  Stephanie C Joachim, Franz H Grus, Daniela Kraft, Kisha White-Farrar, George Barnes, Mike Barbeck, Shahram Ghanaati, Shutong Cao, Byron Li, Martin B Wax
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  ABSTRACT: Increased serum antibodies against heat shock protein 27 (HSP27) have been identified in patients with glaucoma. Immunization with HSP27 caused retinal ganglion cell (RGC) loss in animals. The authors analyzed whether HSP27 immunization not only causes RGC loss but also affects systemic antibody patterns. Rats were immunized with HSP27 and were surveyed for 4, 5, and 6 weeks (groups 1-3). Control animals were humanely killed after 6 weeks (group 4). Intraocular pressure was measured before and 2 and 4 weeks after immunization. Fundus images were taken at the same time. Retinal flatmounts were prepared, and Brn-3a labeled RGCs were counted. Serum was collected during the study to detect antibody patterns against retinal antigens through Western blot analysis and mass spectrometry techniques. Patterns were analyzed by multivariate statistical techniques, and biomarkers were identified with the use of mass spectrometry. No significant changes in intraocular pressure were observed, and no fundus abnormalities were noted. The animals immunized with HSP27 showed lower RGC density than controls (P < 0.05). Two and 4 weeks after immunization, we detected a significant difference in antibody profiles between groups 1 and 4 (P < 0.05) and groups 3 and 4 (P < 0.05). Proteins with different antibody level expression after immunization included heat shock protein 90, alpha-enolase, and glyceraldehyde-3-phosphate dehydrogenase. After immunization with HSP27, animals showed IOP-independent RGC loss and changes in serum antibody patterns. Thus, this model might be a beneficial approach to study the development and effects of anti-retinal antibodies and their involvement in RGC loss.
  Investigative ophthalmology & visual science 06/2009; 50(10):4734-42. · 3.43 Impact Factor
• Article: Cholinergic responses of ophthalmic arteries in M3 and M5 muscarinic acetylcholine receptor knockout mice.

  Adrian Gericke, Veronique G A Mayer, Andreas Steege, Andreas Patzak, Ulrike Neumann, Franz H Grus, Stephanie C Joachim, Lars Choritz, Jürgen Wess, Norbert Pfeiffer
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  ABSTRACT: To determine the functional role of M(3) and M(5) muscarinic acetylcholine receptor subtypes in ophthalmic arteries using gene-targeted mice. Muscarinic receptor gene expression was quantified in murine ophthalmic arteries using real-time PCR. To test the functional relevance of M(3) and M(5) receptors, ophthalmic arteries from mice deficient in either subtype (M3R(-/-), M5R(-/-), respectively) and wild-type controls were isolated, cannulated with micropipettes, and pressurized. Changes in luminal vessel diameter in response to muscarinic and nonmuscarinic receptor agonists were measured by video microscopy. With the use of real-time PCR, all five muscarinic receptor subtypes were detected in ophthalmic arteries. However, mRNA levels of M(1), M(3), and M(5) receptors were higher than those of M(2) and M(4) receptors. In functional studies, after preconstriction with phenylephrine, acetylcholine and carbachol produced concentration-dependent dilations of ophthalmic arteries that were similar in M5R(-/-) and wild-type mice. Strikingly, cholinergic dilation of ophthalmic arteries was almost completely abolished in M3R(-/-) mice. Deletion of either M(3) or M(5) receptor did not affect responses to nonmuscarinic vasodilators such as bradykinin or nitroprusside. These findings provide the first evidence that M(3) receptors are critically involved in cholinergic regulation of diameter in murine ophthalmic arteries.
  Investigative ophthalmology & visual science 05/2009; 50(10):4822-7. · 3.43 Impact Factor
• Article: Sera of glaucoma patients show autoantibodies against myelin basic protein and complex autoantibody profiles against human optic nerve antigens.

  Stephanie C Joachim, Jan Reichelt, Simone Berneiser, Norbert Pfeiffer, Franz H Grus
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  ABSTRACT: The aim of this study was to gain more information about the possible immunological mechanisms in glaucoma. We analyzed the complex autoantibody patterns against human optic nerve antigens in sera of patients with glaucoma and tried to identify important antigens. Sera of 133 patients were included: healthy control subjects (n = 44), primary open-angle glaucoma (n = 44), and normal tension glaucoma patients (n = 45). The sera were tested against Western blots of human optic nerve, and antibody bands were visualized with chloronaphthol. IgG antibody patterns were analyzed by multivariate statistical techniques, and the most significant antigens were identified by mass spectrometry (Maldi-TOFTOF). All subjects, even healthy ones, showed different and complex antibody patterns. Glaucoma groups showed specific up- and down-regulations of antibody reactivities compared to the control group. The multivariate analysis of discriminance found significant differences (P < 0.05) in IgG antibody profiles against human optic nerve antigens between both glaucoma groups and healthy subjects. The identified antigens include: myelin basic protein (up-regulated in the POAG group), glial fibrillary acidic protein (down-regulated in the glaucoma groups), and vimentin (down-regulated in the glaucoma groups in comparison to controls). Using human optic nerve antigen, we were able to demonstrate that complex IgG autoantibody patterns exist in sera of patients with glaucoma. Large correlations between the given and our previous studies using bovine optic nerve antigens could be seen. Furthermore, anti-myelin basic protein antibodies, which can also be detected in patients with multiple sclerosis, were found in sera of glaucoma patients.
  Albrecht von Graæes Archiv für Ophthalmologie 04/2008; 246(4):573-80. · 2.17 Impact Factor
• Article: Analysis of autoantibodies against human retinal antigens in sera of patients with glaucoma and ocular hypertension.

  Jan Reichelt, Stephanie C Joachim, Norbert Pfeiffer, Franz H Grus
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  ABSTRACT: The aim of this study was to show that complex antibody patterns against retinal antigens in sera of patients with glaucoma, found in previous studies, are autoantibodies against human antigens. Sera of 179 patients were collected at the Department of Ophthalmology (University of Mainz, Germany): non-glaucomatous control patients (n=45), primary open-angle glaucoma (n=45), ocular hypertension (n=44), and normal tension glaucoma patients (n=45). The sera were tested against Western blots of human retinal antigens. IgG antibody patterns were analyzed by multivariate statistical techniques, and some significant antigens were identified by mass spectrometry. All subjects, even healthy ones, showed different and complex banding patterns. Glaucoma groups showed up- and down-regulations of antibody reactivities compared to the control group. The multivariate analysis of discriminance found significant differences (p<0.05) in IgG antibody profiles between glaucoma groups, ocular hypertension, and healthy subjects against human retinal antigens. The antigen band at 12 kDa was identified as Histone H4 via mass spectrometry, the 29 kDa band as cellular retinaldehyde-binding protein, and one at 49 kDa as retinal S-antigen. Using human retinal antigen, we demonstrated that complex autoantibody patterns exist in sera of patients with glaucoma. Large correlations with previous studies using bovine retinal antigens could be seen.
  Current Eye Research 03/2008; 33(3):253-61. · 1.28 Impact Factor
• Article: Proteomics in ocular fluids.

  Franz H Grus, Stephanie C Joachim, Norbert Pfeiffer
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  ABSTRACT: The focus of this article is to review recent techniques in proteomic analysis of ocular fluids. These fluids include tears, aqueous humor, and vitreous, they will also be compared to serum analysis. Furthermore, we attempt to summarize some disease correlated biomarkers in ocular fluids that were discovered through different proteomic techniques in eye diseases like dry eye, glaucoma, age-related macular degeneration, uveitis, or diabetic retinopathy. This review is trying to point out the importance of these biomarkers for clinical applications.
  Proteomics. Clinical applications 08/2007; 1(8):876-88. · 1.97 Impact Factor
• Article: Antibodies to alpha B-crystallin, vimentin, and heat shock protein 70 in aqueous humor of patients with normal tension glaucoma and IgG antibody patterns against retinal antigen in aqueous humor.

  Stephanie C Joachim, Kai Bruns, Karl J Lackner, Norbert Pfeiffer, Franz H Grus
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  ABSTRACT: To show the existence of IgG antibodies against retinal antigens in aqueous humor of normal tension glaucoma patients. Forty-two patients were included in this study. Aqueous humor was collected from control subjects (CO; n = 21) and patients with normal tension glaucoma (NTG; n = 21). Western blot methods against bovine retinal antigens were used to detect the IgG antibody patterns. The complex antibody repertoires were analyzed by multivariate statistical techniques. Mass spectrometry was used to identify the most important antigens. Very complex IgG antibody patterns against retinal antigens were found in all analyzed aqueous humor samples. Our multivariate approach could quantify differences in immunoreactivities, and including all peaks, the analysis of discriminance revealed a statistical significant difference between the patterns of the NTG and the CO group (p < 0.001). The antigen band at 21 kDa was identified as alpha B-crystallin, the 57-kDa antigen band as vimentin, and one at 70 kDa as heat shock protein 70. We could demonstrate that complex IgG antibody patterns against retina exist in aqueous humor. The significant differences in the antibody pattern of the glaucoma group compared with the nonglaucoma group in aqueous humor confirm the results of previous studies using sera of glaucoma patients. These differences in antibody patterns might be further evidence for an autoimmune involvement in the pathogenesis of some glaucoma patients.
  Current Eye Research 07/2007; 32(6):501-9. · 1.28 Impact Factor
• Article: Analysis of IgG antibody patterns against retinal antigens and antibodies to alpha-crystallin, GFAP, and alpha-enolase in sera of patients with "wet" age-related macular degeneration.

  Stephanie C Joachim, Kai Bruns, Karl J Lackner, Norbert Pfeiffer, Franz H Grus
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  ABSTRACT: The aim of this study was to compare the IgG antibody patterns against retinal antigens in sera of patients with age-related macular degeneration (AMD) and healthy subjects to learn more about possible immunological aspects of this disease and to identify some of the most important antigens. Sera of 140 patients were analyzed: healthy volunteers (CO, n=101) and patients with "wet" age-related macular degeneration (AMD, n=39). The sera were tested against western blots of bovine retinal antigens. The IgG antibody patterns were analyzed by multivariate statistical techniques and some antigens were identified via LC-MS/MS. All patients showed complex patterns of IgG antibodies against retinal antigens. The discriminant analysis revealed a statistical significant difference between the antibody profiles of the AMD and the CO group (P=0.000023). Not only up-regulations of antigen-antibody-reactivities in the AMD group at some molecular weight ranges, e.g. at 46 and 52 kDa, could be seen, but also down-regulations, e.g. at 18 and 36 kDa. The 18 kDa antigen band was identified as alphaB-crystallin, the band at 46 kDa as alpha-enolase, and one at 52 kDa as glial fibrillary acidic protein. We could demonstrate that both groups (wet AMD and CO) show complex IgG antibody patterns against retinal antigens, which are highly specific for each group. This provides further hints for the immunological basis of the disease. These changes in the antibody profiles in "wet" AMD could represent a secondary response to retinal damage or can play a causative role in the disease.
  Albrecht von Graæes Archiv für Ophthalmologie 06/2007; 245(5):619-26. · 2.17 Impact Factor
• Article: IgG antibody patterns in aqueous humor of patients with primary open angle glaucoma and pseudoexfoliation glaucoma.

  Stephanie C Joachim, Diana Wuenschig, Norbert Pfeiffer, Franz H Grus
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  ABSTRACT: There has been growing body of evidence indicating an immunological component in the pathogenesis of glaucoma. Several studies found specific antibodies in sera of glaucoma patients. Recently, we detected antibody profiles in aqueous humor of patients with normal tension glaucoma that showed significant differences when compared to control subjects. The aim of this study was to compare the IgG antibody patterns against retinal antigens in aqueous humor of patients with primary open angle glaucoma, pseudoexfoliation glaucoma, and control subjects then to identify some of the important biomarkers of this study. Aqueous humor of 44 patients was analyzed: 15 patients with primary open angle glaucoma (POAG), 14 patients with pseudoexfoliation glaucoma (PEX), and 15 control subjects (CO). The aqueous was tested against western blots of bovine retinal antigens. The IgG antibody patterns were analyzed by multivariate statistical techniques. Some of the important biomarkers were identified via mass spectrometry (Maldi-TOFTOF). All patients showed complex patterns of IgG antibodies against retinal antigens. The discriminant analysis revealed a statistically significant difference between the antibody profiles of the POAG and the CO group (p=0.00018). There was also a statistically significant difference between the antibody profiles of the PEX and the CO group (p=0.0013). Not only were up-regulations in the glaucoma groups observed, compared to controls, but also down-regulations. There was no significant difference between the antibody patterns of the POAG and PEX group. The identified biomarkers included heat shock protein 27, alpha-enolase, actin, and GAPDH. We could show significant differences between the IgG antibody profiles of the glaucoma groups (PEX and POAG) and controls. The analysis of intraocular antibodies could provide further hints for autoimmune involvement in glaucoma.
  Molecular vision 02/2007; 13:1573-9. · 2.20 Impact Factor
• Article: Serum autoantibodies to alpha-fodrin are present in glaucoma patients from Germany and the United States.

  Franz H Grus, Stephanie C Joachim, Kai Bruns, Karl J Lackner, Norbert Pfeiffer, Martin B Wax
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  ABSTRACT: 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. 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. 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). 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.
  Investigative Ophthalmology &amp Visual Science 04/2006; 47(3):968-76. · 3.60 Impact Factor
• Article: Autoantibodies in patients with glaucoma: a comparison of IgG serum antibodies against retinal, optic nerve, and optic nerve head antigens.

  Stephanie C Joachim, Norbert Pfeiffer, Franz H Grus
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  ABSTRACT: The aim of this study was to analyze and compare the entire IgG autoantibody patterns against different ocular antigens (retina, optic nerve, and optic nerve head) in sera of glaucoma patients and healthy subjects. Sixty-six patients were included in this study: healthy volunteers without any ocular disorders (CO, n=30), patients with primary open-angle glaucoma (POAG, n=19), and patients with normal-tension glaucoma (NTG, n=17). The sera were tested for antibodies against retinal, optic nerve, and optic nerve head tissues. Immunodetection was performed using 4-chloro-1-naphthol staining. The autoantibody patterns were digitized and subsequently analyzed by multivariate statistical techniques. All patients showed a complex repertoire of IgG antibodies against retinal, optic nerve, and optic nerve head antigens. The analysis of discriminance revealed a statistically significant differences between the patterns of all three groups. Our multivariate approach could quantify the differences in immunoreactivities of patient sera against the three antigens. The POAG group had the most significant difference against retinal antigens (P=0.0021) compared with the other antigens. In the NTG group the highest reactivity appeared against optic nerve head (P=0.00053) and optic nerve (P=0.0025). All groups showed different and complex antibody patterns against the three ocular tissues. These autoantibodies are highly specific for each patient group. The analysis of these patterns could provide further information about possible autoimmune mechanisms in the pathogenesis of glaucoma.
  Albrecht von Graæes Archiv für Ophthalmologie 09/2005; 243(8):817-23. · 2.17 Impact Factor
• Article: Complex autoantibody repertoires in patients with glaucoma.

  Franz H Grus, Stephanie C Joachim, Esther M Hoffmann, Norbert Pfeiffer
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  ABSTRACT: Glaucoma is one of the leading causes for blindness in the world. It is characterized by a progressive loss of retinal ganglion cells. An elevated intraocular pressure cannot explain the disease in all subjects. Autoimmune mechanisms maybe involvemed in the pathogenesis of the disease. The aim of our study was to analyze the IgG autoantibody repertoires in sera of glaucomatous subjects against optic nerve antigens. Ninety-four subjects were included in this comparative cross-sectional study of healthy (CTRL), primary-open-angle-glaucoma (POAG), ocular-hypertension (OHT), and normal-tension-glaucoma (NTG) volunteers. Sera of subjects were tested against western blots of optic nerve antigens. For each western blot, a densitograph was built by digital image analysis and subsequently a multivariate analysis of discriminance was performed. Complex IgG autoantibody repertoires could be found in all subjects, even in healthy subjects. The multivariate analysis of discriminance can test for statistical differences between the groups using the whole complex staining pattern for the calculation. A significant difference between all groups against optic nerve antigens was found. The NTG group had the highest variance from controls (p<0.01). This study demonstrates immunological effects in POAG and NTG and may provide further evidence for an involvement of autoantibodies in the pathogenesis of both NTG and POAG. Using the techniques presented in this study, the differences in the complex autoantibody repertoires were assessed by means of statistical analysis. Further studies are needed to determine whether these changes in autoantibodies could be helpful in the diagnosis of glaucoma.
  Molecular vision 02/2004; 10:132-7. · 2.20 Impact Factor
• Article: Autoimmunity and glaucoma.

  Franz H Grus, Stephanie C Joachim, Diana Wuenschig, Jochen Rieck, Norbert Pfeiffer
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  ABSTRACT: Elevated intraocular pressure does not explain glaucoma in all patients, but there is information that autoimmune mechanisms may be involved in this disorder. This review attempts to reveal the findings about specific changes in autoantibody profiles in glaucoma patients and their possible role in glaucoma. Considering that these changes in natural autoimmunity can be found consistently among different study populations, it might be a promising new tool for glaucoma detection.
  Journal of Glaucoma 17(1):79-84. · 1.78 Impact Factor