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The role of T lymphocytes in uveitis
Tuesday, Sep 22, 1992 Palazzo Dei Congressi/A
X ICER Abstracts SEPTEMBER
CODE: G-5
GENERAL
224
1
22!DJESDAY
The poiymerase chain reaction method in the diagnosis of viral uveitis M. Usui, N. Usui, J. Sakai , H.Minoda Department of Ophthalmology, Tokyo Medical CHAIRpERsoNs:
LARRY A. WNOSO JOHN FORRESTER
(USA) (UK)
Usui
(Japan) i
T-cell RV. Calder (UK) Inflammation L.A. Donoso 4
12:oo
6
IF40
(USA)
TheRole t” uwui A.F. De Vos. M.A.C. Van Hare”. K. Verbage”. S. Van Deventer, A. Kijlstra and R. Hoekzema (The Netherlands) A.G.
Secchi.
of Uveltls M.S. Tognon
and
S. Miorin
ton I” Poatehor J.V. Forrester. J.L. Liversidge and P.G. McMenamin (UK, Australia)
Hospital,
Tokyo,
Japan
To make an etiological diagnosis of intraocular inflammation or uveitis of viral origin is us”ally difficult in tbe uveitis clinic. Recently, the polymeram chain reaction (PCR) method has made it possible to rapidly determine the etiological agent in the early stage of uveitis by “sing samples of intraocular fluid (IOF), cerebtospinal fluid (CSF), or clinical materials. In this paper, we present PCR methods for the diagnosis of uveitis due to several kinds of herpes virus. The primers used for the PCR were DNA segments from herpes simplex virus (HSV), vaticella-roster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus -6 (HHV-6). Ninety-seven IOF samples and 40 CSF specimens from patients with suspected viral uveitis were examined, and the intraocular tissue from 15 autopsy eyes were also investigated by the PCR method. The results were as follows: 1) VZV DNA was found in IOF from 4/6 patients with Kirisawa-type uveitis (acute retinal necrosis) and HSV DNA was found in 2 other patients. 2) VZV DNA was also see” in IOF from two cases of zoster ophthalmia with uveitis, and in IOF from a “veitis patient without roster eruptions. 3) EBV DNA was detected in CSF from 18/21 Vogt-Koyanagi-Harada disease patients. 4) Herpes virus DNA were found in the retina or the iris and ciliary body of 9/15 autopsy eyes. Our data suggest that herpes viruses may play the main role as the causative agents of viral uveitis, and that the PCR method is a very useful tool for establishing an etiological diagnosis rapidly.
TATION
M.
College
(Italy)
Uvettta
225
2 THE
ROLE
Calder.
OF T LYMPHOCYTES
IN UVElTIS.
V.
Dept. Clinical St, London
Science, EClV 9AT.
Institute UK.
of Ophthalmology,
17-25
Cayton
uveitis is thought to be a T-cell mediated autoimmune disease due to the predominance of CD4+T-cells and an increased expression of HLA-DR molecules within the inflammatory lesions of the retina. In addition, the effectiveness of cyclosporin A in treating many uveitts patients suggests that T lymphocytes are important in the pathogenesfs of this disease. Recent availability of various T cell-related markers has ailowed us to examine the peripheral biood for the presence of activated T-cells in uveltis patients compared with normals. The pattern of T-cell antigen receptors expressed within the activated, CD4+T-cell population has also been examined and the production of lympboktnes measured. to find out if the blood can be used in the clinical monttoring of the disease. Another approach for studying the possible T cell-mediated mechanisms within the retina has been to use the model experimental autoimmune uveoretinttis [EAU) in Lewis rats, due to the similarities in both the immunopathology and in the bloodretinal barriers between human and rat. CD4+T-cell lines reactive with retinal S antigen have been examined for their pattern of lymphokine production and their ability to adoptively transfer disease. The infiltrating lymphocytes have been isolated from the retinae during EAU and have been characterised. The implications of these hndings both in EAU and in uveitis will Posterior
discussed.
226
3 AUTOANTIGENS Donoso. Research Street,
INVOLVED
L.A. Department, Philadelphia,
IN
INTRAOCULAR
Wils Eye Pennsylvania
Hospital,
INFLAMMATION 900
Walnut
The role of ocular antigens in the pathogenesis of inflammatory diseases has been investigated since in this century. The most potent of these autoantigens, to date, have been identified, isolated and characterized from retinal tissue.
early
S-Antigen, IRBP, rhodopsin, and phosducin are perhaps the most well-characterized of the retinal autoantigens capable of eliciting an inflammatory response. Much is knovn concerning the molecular characterization of each of these molecules as well as the identification of innnunofogically relevant sites within the molecule. In addition, several of these retinal proteins, such as S-Antigen! rhodopain, and phosducin, play a fundamental role in the phototransduction of vision. Although the involvement of these molecules in the pathogencsis of human ocular inflammatory diseases has not been firmly established, mutations in the rhodopsin gene have been identified in one form of retinitis pigmentosa. Some patients with systemic ntalignancy may have cancer associated retinopathy which may have an autoimmune basis. A review of these various retinal autoantigens will be presented.
S.69
X ICER Abstracts SEPTEMBER
CODE: G-5
GENERAL
224
1
22!DJESDAY
The poiymerase chain reaction method in the diagnosis of viral uveitis M. Usui, N. Usui, J. Sakai , H.Minoda Department of Ophthalmology, Tokyo Medical CHAIRpERsoNs:
LARRY A. WNOSO JOHN FORRESTER
(USA) (UK)
Usui
(Japan) i
T-cell RV. Calder (UK) Inflammation L.A. Donoso 4
12:oo
6
IF40
(USA)
TheRole t” uwui A.F. De Vos. M.A.C. Van Hare”. K. Verbage”. S. Van Deventer, A. Kijlstra and R. Hoekzema (The Netherlands) A.G.
Secchi.
of Uveltls M.S. Tognon
and
S. Miorin
ton I” Poatehor J.V. Forrester. J.L. Liversidge and P.G. McMenamin (UK, Australia)
Hospital,
Tokyo,
Japan
To make an etiological diagnosis of intraocular inflammation or uveitis of viral origin is us”ally difficult in tbe uveitis clinic. Recently, the polymeram chain reaction (PCR) method has made it possible to rapidly determine the etiological agent in the early stage of uveitis by “sing samples of intraocular fluid (IOF), cerebtospinal fluid (CSF), or clinical materials. In this paper, we present PCR methods for the diagnosis of uveitis due to several kinds of herpes virus. The primers used for the PCR were DNA segments from herpes simplex virus (HSV), vaticella-roster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus -6 (HHV-6). Ninety-seven IOF samples and 40 CSF specimens from patients with suspected viral uveitis were examined, and the intraocular tissue from 15 autopsy eyes were also investigated by the PCR method. The results were as follows: 1) VZV DNA was found in IOF from 4/6 patients with Kirisawa-type uveitis (acute retinal necrosis) and HSV DNA was found in 2 other patients. 2) VZV DNA was also see” in IOF from two cases of zoster ophthalmia with uveitis, and in IOF from a “veitis patient without roster eruptions. 3) EBV DNA was detected in CSF from 18/21 Vogt-Koyanagi-Harada disease patients. 4) Herpes virus DNA were found in the retina or the iris and ciliary body of 9/15 autopsy eyes. Our data suggest that herpes viruses may play the main role as the causative agents of viral uveitis, and that the PCR method is a very useful tool for establishing an etiological diagnosis rapidly.
TATION
M.
College
(Italy)
Uvettta
225
2 THE
ROLE
Calder.
OF T LYMPHOCYTES
IN UVElTIS.
V.
Dept. Clinical St, London
Science, EClV 9AT.
Institute UK.
of Ophthalmology,
17-25
Cayton
uveitis is thought to be a T-cell mediated autoimmune disease due to the predominance of CD4+T-cells and an increased expression of HLA-DR molecules within the inflammatory lesions of the retina. In addition, the effectiveness of cyclosporin A in treating many uveitts patients suggests that T lymphocytes are important in the pathogenesfs of this disease. Recent availability of various T cell-related markers has ailowed us to examine the peripheral biood for the presence of activated T-cells in uveltis patients compared with normals. The pattern of T-cell antigen receptors expressed within the activated, CD4+T-cell population has also been examined and the production of lympboktnes measured. to find out if the blood can be used in the clinical monttoring of the disease. Another approach for studying the possible T cell-mediated mechanisms within the retina has been to use the model experimental autoimmune uveoretinttis [EAU) in Lewis rats, due to the similarities in both the immunopathology and in the bloodretinal barriers between human and rat. CD4+T-cell lines reactive with retinal S antigen have been examined for their pattern of lymphokine production and their ability to adoptively transfer disease. The infiltrating lymphocytes have been isolated from the retinae during EAU and have been characterised. The implications of these hndings both in EAU and in uveitis will Posterior
discussed.
226
3 AUTOANTIGENS Donoso. Research Street,
INVOLVED
L.A. Department, Philadelphia,
IN
INTRAOCULAR
Wils Eye Pennsylvania
Hospital,
INFLAMMATION 900
Walnut
The role of ocular antigens in the pathogenesis of inflammatory diseases has been investigated since in this century. The most potent of these autoantigens, to date, have been identified, isolated and characterized from retinal tissue.
early
S-Antigen, IRBP, rhodopsin, and phosducin are perhaps the most well-characterized of the retinal autoantigens capable of eliciting an inflammatory response. Much is knovn concerning the molecular characterization of each of these molecules as well as the identification of innnunofogically relevant sites within the molecule. In addition, several of these retinal proteins, such as S-Antigen! rhodopain, and phosducin, play a fundamental role in the phototransduction of vision. Although the involvement of these molecules in the pathogencsis of human ocular inflammatory diseases has not been firmly established, mutations in the rhodopsin gene have been identified in one form of retinitis pigmentosa. Some patients with systemic ntalignancy may have cancer associated retinopathy which may have an autoimmune basis. A review of these various retinal autoantigens will be presented.
S.69