Current Eye Research
Volume I I supplement 1992, 193- 195 ~~
Soluble interleukin-2 receptors in retinal vasculitis P.I.Murray and D.W.Young
Curr Eye Res Downloaded from informahealthcare.com by North Carolina State University on 10/30/14 For personal use only.
Birmingham and Midland Eye Hospital, Church Street, Birmingham B3 2NS, UK
ABSTRACT Soluble interleukin-2 receptor (sIL-2R)levels were measured in the serum of 27 patients with retinal vasculitis, 16 with vasculitis purely isolated to the eye (RV) and 11 with vasculitis associated with a systemic inflammatory disease (RV+SID).Levels of sIL-2R were statistically significantly increased (p 986, SD 845 U/ml, p = 0.013) only in the RV+SIDgroup as compared to healthy controls. The highest levels being found in patients with sarcoidosis (p 1436, SD 1083 U/ml). There was no correlation with disease activity or with systemic corticosteroid therapy. Serum sIL-2R measurements appearto be of limited use in the management of patients with r e t d vasculitis, but may be of value in those patients with sarcoidosis. Longitudinal measurements with larger numbers of patients are required to confirm this. Serum slL-2R levels were also statisticall significantly increased (p 843, SD 171 U/ml, p < 0.0081 ) in 21 patients with Fuchs' hetemchromic cyclitis. As this is a c h i c condition with mild inflammatory activity and no associated systemic disease,the explanation for this finding is unknown.
the management of intraocularinflammation.If they Q not controlthedegreeofinflammahon . ,or arconly effwiveat levds intolerable to the patient, then immunosuppressiveagmts can be intmduced, such as cyclosporin A. Ihe m a m e m a u of sctlltll sIL-2R levels may have a role to play in predictingdapscs in these patients and in monitoring the effect of diffaent tmtmcnt modalities. Results would be compared to healthy controls and to another type of intraocular inflammation clinically distinct from retinal vasculitis,Fuchs' heoerochromic cyclitis (FHC). FHC comprisesabout 3% of all cases of uveitis (9) and pursues a chronic coursewith only mild inflammatory activity. Its aetiology is unknown, but the condition is Bssociatcdwith disturbancesof intraocular immune mechanisms (10.11).
INTRODUCITON Serum soluble IL-2 receptor (sIL-2R)level is a sensitive and quantitative marker of circulating peripheral blood mononuclear cell activation (1). Elevated sIL-2R levels are found in diseases with a vasculitic component, such as rheumatoid arthritis (2) and systemic lupus erythematosus (3),high levels correlating with disease activity (2)and disease progression (3).At present, there are no markers for vasculitis affecting the eye nor any that consistently reflect disease activity. Recent literature regarding sIL-2R and intraocular inflammation appears unclear and contradictory (4-7). Rather than estimate serum sIL-2R levels in a wide variety of uveitis syndromes it was decided to look at patients with retinal vasculitis. 'Ihis is a potentially sight threatening group of diseases with macular oedema the main reason for permanent visual loss. Retinal vasculitis, although not a specific diagnostic entity, may be subdivided into disease purely isolated to the eye (RV) or as part of a systemic inflammatory diseases process (RV + SID)(8).The pathogenesis is poorly understood, although an immunological basis is suspected (8). Systemic corticosteroids (with their well known side effects) are the most useful drugs in
PATIENTS AND MEI'HODS All patients w t z recruited from the Uvcitis Clinic at the Birmingham and Midland Eye Hospital.Informed conscnt was obtained and a serum samplecollededand stored at -2o'C. 'Ihe patient group comprised the following: (a) RV, 9F 7h4 aged 1565 years (p 29), 10 idiopathic and 6 with intamcdiak uveitis (b) RV+SID,7F 4M aged 21-58 year^ (p 41). 5 VVUI sarcoidosis, 4 Belqet's syndrome (fulrilling the critaia of the Ekhwt's UK Study Group), 1 demyelinatingdisease, 1 chronic active hepatitis (c) FHC; 11F 1OM aged 16454 years (p 42) and (d) healthy controls; 1OF 1OM aged 18-73 years (p 43). Patients with RV as a result of infection, ischaemia or malignancy werc excluded from the study. Inflammatory activity in the RV and RV+SIDgroups was classified according to a previously published scoring system (8). All sera were analysed within 2-6 months of venesection and no serum sample had previously undergone a freezelthaw cycle. sIL-2R levels were measured using a commercially availableELISA (Tcell SciwxS, Cambridge, MA)which is regarded as the gold standard for this investigation. All measurementswere carried out by one of the authors (PIM).
Receivcd on November 26. 1991; accepted on January 27. 1992 ~
0 Oxford University Press
193
Current Eye Research
Curr Eye Res Downloaded from informahealthcare.com by North Carolina State University on 10/30/14 For personal use only.
RESULTS sIL2R levels arc summarised in Table 1. The sIL-2R values in each group wclrt sbewedanddid nat amfam toanormal distribution,thaeforr statistical analysis was perfarmed using a non' W; thc Mann-Whitney U Test. Ofthe paficats with rttinal ~sculitis,only the RV+SJDgroup showcd a s w i s b l l y siplicant incnaJein suum &2R levels as compared to m m l s (p = 0.013). The highest values being found in thosepathts with sarcoidosis (p 1436, SD 1083 U/ml). n#e was also a highly statistically signiticant increase in m m &2R levels in the FHC group (p < 0.OOOl). All FHC patients had mild anterior chamber activity and none w e ~ hking e systanic c u t i m d s . In the RV and RV+SID patient groups, no correlation could be found with regards to dcgFteofinflammatcnyactivityoruseofsystcmic&costeroid therapy at the timeof venesection (Tables 2 and 3).
DISCUSSION Previous reports on m m sIL2-R in uveitis have shown statistically signtficant incEeased levels in patients with sarcoidosis(4),juvenile chronic arthritis-associateduveitis (3, FHC (5)and Behw's disease (6,7). Normal levels have been detected in patients with intermediate uveitis (5,7), which is in agreement with this study. However, this study could not confirm the previously documented raised sL2R levels in Behpt's disease (6,7), but this may be due to the small numbers of patients tested (n = 4). In the RV+SIDgroup, high levels w a e sten in patients with SarcOidOSis c o n h i n g
previous work by Rombaum et al. (4). Unfortunately,with regard to their patients with Sarcoidosis, this latter study failed to mention: (i) the exact type of uveitis, (ii) the degree of clinical inflammation,and (iii) whether ar not systemiccorticosteroids were being used. Howmr, they did find that the location of Table 2: Serum sIL2R levels, inflammatoryactivity and systemic steroid therapy in patients with retinal vasculitis patients
Idiopathic 1 2 3 4 5 6 7 8
9 10 Intermediate 1 2 3 4 5
6
sIL2R (Wml)
Mean
SD
RV Idiopathic
( n = 16) ( n = 10) (n = 6)
201-1201 354-1201 201-942
548 563 522
241 78 254
RV+SID sarcoidosis
Behcel
( n = 11) (n = 5) (n = 4)
303-3363 851-3363 375-717
986 1436 531
845* 1083 161
FHC
(n=21)
500-1203 276792
843 479
In-
CONTROLS (n=20)
1717 157
RV: ntinal vasculitis, RV+SID:retinal vasculitis and systemic inflammatorydiscase, FHC Fuchs' heterochromicc clitis All difkmces not significant as comparedto amtm s except *p = 0.013, tp < O.OOO1
r
194
Systemic Steroids
354 420 439 442 444 466 557 626 687 1201
Moderate
No No
201 329 501 573 586 942
Moderate
Moderate Moderate Mild Mild Severe Mild Modgate
Moderate Moderate
YeS
No No No No No No No YeS YeS
Moderate Mild
No
Moderate Moderate Moderate
No No
YeS
Table 3: Serum sIL2R levels, inflammatoryactivity and systemic steroid therapy in patients with retinal vasculitis and systemicinflammatory disease sIL-~R (U/ml)
Inflammatory Activity*
851 883 950 1132 3363
Moderate
YeS
Moderate
No
Severe Modaate
No
M&k
YeS
375 420 613 717
Mild Pronounced
Moderate
Yes YeS No
Pronounced
YeS
Demyelination 1 303
Mild
No
CAH 1
Mild
YeS
Patients
Range
Inflammatory Activity*
*see Ref. (8)
Table 1. &2R levels in serum of patients with h n a l vasculitis and Fuchs' hctaochromic cyclitis WtientOroup
sIL-~R (U/ml)
Saraidosis 1 2 3 4
5
% 1 2 3 4
1244
*see Ref. (8), CAH:chronic active hepatitis
Systemic Steroids
YeS
Curr Eye Res Downloaded from informahealthcare.com by North Carolina State University on 10/30/14 For personal use only.
Current Eye Research intraocular inflammation did not appear to influence sIL-2R levels. It is known that sIL-2R levels are raised in immune mediated states and may reflect the intensity of the response (2) and the extent of the disease (3). It Seems clear that sarcoidosis, as an immune mediated systemic disease, is likely to have raised sIL2R. As others have shown the asssociation between sIL-2R levels and disease activity (2,3) it is possible that these receptors could be used to monitor the activity of sarcoidosis and hence its response to treatment. So far, clinical features are the only measure of disease activity. Though important, they tend to reflect gross and often late changes in the disease process. The finding of raised sIL-2R levels in FHC is unexpected but confirms the previous work of Amcker-Mettinger et al. (3, (although Rosenbaum et al. (4) found normal levels in 2 patients in their study). The significance of this is not known but gives further evidence to the theory of immune dysregulation in this condition. It suggests that disease purely localised to the eye can give rise to systemic (peripheral blood) abnormalities. A similar situation has been previously documented, when activated T cells were found in the peripheral blood of some patients with idi-c uveitis (12). This implies that the interpretation of a negative test as a indicator for systemic disease in uveitis patients may indicate that the test was inappropriate or the disease was not present, rather than the eye (asa small organ) having a limited impact on the rest of the body. The wide variation in sIL-2R levels is a feature of this study. For example, whilst there was no overall difference between the values of controls and the RV group, the spread of values in the disease group is so wide (RV 201-1201, controls 276-792 U/ml) that some of the cases must be regarded as having abnormally high levels. Perhaps more emphasis should be placed on the disease activity rather than the actual diagnosis when assessing the results of this test. As sIL-2R levels reflect activity of the immune state rather than inflammation per se,it can be anticipated that there will be, on occasions, a disparity between the clinical findings and sIL-2R levels. If there is a strong association between raised sIL-2R levels and subsequent inflammatory damage then these levels could be used as a guide to the initiation and monitoring of mtxnent. In FHC, where the grumbling inflammation causes visual loss in the form of cataract (which is readily treatable), there is little reason to instigate more aggressive treatment modalities. However, there may be a stronger case for sarcoidosis especially if sIL-2R levels could be shown to predict relapses of inflammation.
Despite the small numbers of patients in this study, ntinal vasculitis in association with SafCOidOSiS is a particular subgroup that may wanant further investigatim on a longitudinal basis. FHC remains an enigma, and futurc rcscaxh in this department is aimed at trying to unravel the mysteries of this condition. ACKNOWLEDGEME"
We are grateful to Helen Jones for statistical assistance.
CORRESPONDINGAUTHOR Philip I. Murray, Ac;sdemic Unit of Ophthalmology, Birmingham and Midland Eye Hospital,Church Street, Birmingham B3 2NS,UK. REFERENCES 1. Rubin, L.A. and Nelson, D.L. (1990) The soluble interleukin-2 receptor: biology, function, and clinical application. AM. Intern. Med. U,6 19-627. 2 . Symons, J.A., Wood, N.C., Di Giovine, F.S. and Duff, G.W. (1988) Soluble IL-2 receptor in rheumatoid arthritis. Correlation with disease activity, IL-1 and IL-2 inhibition. J. Immunol. 141,2612-2618. 3. Manoussakis, M.N., Papado ulos, G.K., Drosos, A.A. and Moutsopoulos, H.M. (19& Soluble interleukin 2 receptor molecules in the serum of patients with autoimmune diseases. Clin. Immunol. Immunopathol. N, 32 1-332. 4. Rosenbaum, J.T., Tilden, M . E and W e , A. (1990) Soluble interleukin-2 levels in patients with uveitis. In 'Ocular Immunology Today', (Eds. Usui, M.,Ohno, S. and Aoki, K.). Pp. 77-80, Excerpta Med~ca,Amsterdam. 5 . Arocker-Mettinger, E, Asenbauer, T., Ulbrich, S. and Grabner, G. (1990) Serum interleukin 2-receptor levels in uveitis. Curr. Eye Res. 9 , 2 5 - 2 9 . 6. Akoglu, T.F., Direskeneli, H., Yazici, H.and Lawrence, R. (1990) TNF, soluble IL-2R and soluble CD-8 in Behget's disease. J. Rheumatol. l7, 1107-1 108. 7. BenD., l3arak, V.,Kalichman, I. and Maftzir, G. (1991) Interleukin-2 receptor in Behst's disease - effect of cyclosporin A. Invest. Ophthalmol. Vis. Sci. 32, 935. 8. Dumonde, D.C., KaspGrochowska, E., Graham,E, Sanders, M.D., Faure, J-P., de Kozak, Y.and van Tuyen, V. (1982) Anti-retinal autoimmunity and circulating immune complexes in patients with retinal vasculitis. Lancet, ii,787-792. 9. Murray, P. (1986) Serum autoantibodies and uveitis. Br. J. Ophthalmol. Zn, 266-268. 10. Murray, P.I., Hoekzema, R., van Haren, M.A.C., de Hon, F.D. and Kijlstra, A. (1990) Aqueous humor interleukin-6 levels in uveitis. Invest. Ophthalmol. Vis. 917-920. Sci. 11. Murray, P.I., Hoekzema, R., Luyendijk, L, Konings, S. and Kijlstra, A. (1990) Analysis of aqueous humor immunoglobulin G in uveitis by enzyme-linked immunombent assay, isoelectric focusing and immunoblotting. Invest. Ophthalmol. Vis. Sci. 2129-2135. 12. Deschenes, J., Char, D.H. and Kaleta, S. (1988) Activated T lymphocytes in uveitis. Br. J. Ophthalmol. 22, 83-87. ~~~
a,
a,
195
Volume I I supplement 1992, 193- 195 ~~
Soluble interleukin-2 receptors in retinal vasculitis P.I.Murray and D.W.Young
Curr Eye Res Downloaded from informahealthcare.com by North Carolina State University on 10/30/14 For personal use only.
Birmingham and Midland Eye Hospital, Church Street, Birmingham B3 2NS, UK
ABSTRACT Soluble interleukin-2 receptor (sIL-2R)levels were measured in the serum of 27 patients with retinal vasculitis, 16 with vasculitis purely isolated to the eye (RV) and 11 with vasculitis associated with a systemic inflammatory disease (RV+SID).Levels of sIL-2R were statistically significantly increased (p 986, SD 845 U/ml, p = 0.013) only in the RV+SIDgroup as compared to healthy controls. The highest levels being found in patients with sarcoidosis (p 1436, SD 1083 U/ml). There was no correlation with disease activity or with systemic corticosteroid therapy. Serum sIL-2R measurements appearto be of limited use in the management of patients with r e t d vasculitis, but may be of value in those patients with sarcoidosis. Longitudinal measurements with larger numbers of patients are required to confirm this. Serum slL-2R levels were also statisticall significantly increased (p 843, SD 171 U/ml, p < 0.0081 ) in 21 patients with Fuchs' hetemchromic cyclitis. As this is a c h i c condition with mild inflammatory activity and no associated systemic disease,the explanation for this finding is unknown.
the management of intraocularinflammation.If they Q not controlthedegreeofinflammahon . ,or arconly effwiveat levds intolerable to the patient, then immunosuppressiveagmts can be intmduced, such as cyclosporin A. Ihe m a m e m a u of sctlltll sIL-2R levels may have a role to play in predictingdapscs in these patients and in monitoring the effect of diffaent tmtmcnt modalities. Results would be compared to healthy controls and to another type of intraocular inflammation clinically distinct from retinal vasculitis,Fuchs' heoerochromic cyclitis (FHC). FHC comprisesabout 3% of all cases of uveitis (9) and pursues a chronic coursewith only mild inflammatory activity. Its aetiology is unknown, but the condition is Bssociatcdwith disturbancesof intraocular immune mechanisms (10.11).
INTRODUCITON Serum soluble IL-2 receptor (sIL-2R)level is a sensitive and quantitative marker of circulating peripheral blood mononuclear cell activation (1). Elevated sIL-2R levels are found in diseases with a vasculitic component, such as rheumatoid arthritis (2) and systemic lupus erythematosus (3),high levels correlating with disease activity (2)and disease progression (3).At present, there are no markers for vasculitis affecting the eye nor any that consistently reflect disease activity. Recent literature regarding sIL-2R and intraocular inflammation appears unclear and contradictory (4-7). Rather than estimate serum sIL-2R levels in a wide variety of uveitis syndromes it was decided to look at patients with retinal vasculitis. 'Ihis is a potentially sight threatening group of diseases with macular oedema the main reason for permanent visual loss. Retinal vasculitis, although not a specific diagnostic entity, may be subdivided into disease purely isolated to the eye (RV) or as part of a systemic inflammatory diseases process (RV + SID)(8).The pathogenesis is poorly understood, although an immunological basis is suspected (8). Systemic corticosteroids (with their well known side effects) are the most useful drugs in
PATIENTS AND MEI'HODS All patients w t z recruited from the Uvcitis Clinic at the Birmingham and Midland Eye Hospital.Informed conscnt was obtained and a serum samplecollededand stored at -2o'C. 'Ihe patient group comprised the following: (a) RV, 9F 7h4 aged 1565 years (p 29), 10 idiopathic and 6 with intamcdiak uveitis (b) RV+SID,7F 4M aged 21-58 year^ (p 41). 5 VVUI sarcoidosis, 4 Belqet's syndrome (fulrilling the critaia of the Ekhwt's UK Study Group), 1 demyelinatingdisease, 1 chronic active hepatitis (c) FHC; 11F 1OM aged 16454 years (p 42) and (d) healthy controls; 1OF 1OM aged 18-73 years (p 43). Patients with RV as a result of infection, ischaemia or malignancy werc excluded from the study. Inflammatory activity in the RV and RV+SIDgroups was classified according to a previously published scoring system (8). All sera were analysed within 2-6 months of venesection and no serum sample had previously undergone a freezelthaw cycle. sIL-2R levels were measured using a commercially availableELISA (Tcell SciwxS, Cambridge, MA)which is regarded as the gold standard for this investigation. All measurementswere carried out by one of the authors (PIM).
Receivcd on November 26. 1991; accepted on January 27. 1992 ~
0 Oxford University Press
193
Current Eye Research
Curr Eye Res Downloaded from informahealthcare.com by North Carolina State University on 10/30/14 For personal use only.
RESULTS sIL2R levels arc summarised in Table 1. The sIL-2R values in each group wclrt sbewedanddid nat amfam toanormal distribution,thaeforr statistical analysis was perfarmed using a non' W; thc Mann-Whitney U Test. Ofthe paficats with rttinal ~sculitis,only the RV+SJDgroup showcd a s w i s b l l y siplicant incnaJein suum &2R levels as compared to m m l s (p = 0.013). The highest values being found in thosepathts with sarcoidosis (p 1436, SD 1083 U/ml). n#e was also a highly statistically signiticant increase in m m &2R levels in the FHC group (p < 0.OOOl). All FHC patients had mild anterior chamber activity and none w e ~ hking e systanic c u t i m d s . In the RV and RV+SID patient groups, no correlation could be found with regards to dcgFteofinflammatcnyactivityoruseofsystcmic&costeroid therapy at the timeof venesection (Tables 2 and 3).
DISCUSSION Previous reports on m m sIL2-R in uveitis have shown statistically signtficant incEeased levels in patients with sarcoidosis(4),juvenile chronic arthritis-associateduveitis (3, FHC (5)and Behw's disease (6,7). Normal levels have been detected in patients with intermediate uveitis (5,7), which is in agreement with this study. However, this study could not confirm the previously documented raised sL2R levels in Behpt's disease (6,7), but this may be due to the small numbers of patients tested (n = 4). In the RV+SIDgroup, high levels w a e sten in patients with SarcOidOSis c o n h i n g
previous work by Rombaum et al. (4). Unfortunately,with regard to their patients with Sarcoidosis, this latter study failed to mention: (i) the exact type of uveitis, (ii) the degree of clinical inflammation,and (iii) whether ar not systemiccorticosteroids were being used. Howmr, they did find that the location of Table 2: Serum sIL2R levels, inflammatoryactivity and systemic steroid therapy in patients with retinal vasculitis patients
Idiopathic 1 2 3 4 5 6 7 8
9 10 Intermediate 1 2 3 4 5
6
sIL2R (Wml)
Mean
SD
RV Idiopathic
( n = 16) ( n = 10) (n = 6)
201-1201 354-1201 201-942
548 563 522
241 78 254
RV+SID sarcoidosis
Behcel
( n = 11) (n = 5) (n = 4)
303-3363 851-3363 375-717
986 1436 531
845* 1083 161
FHC
(n=21)
500-1203 276792
843 479
In-
CONTROLS (n=20)
1717 157
RV: ntinal vasculitis, RV+SID:retinal vasculitis and systemic inflammatorydiscase, FHC Fuchs' heterochromicc clitis All difkmces not significant as comparedto amtm s except *p = 0.013, tp < O.OOO1
r
194
Systemic Steroids
354 420 439 442 444 466 557 626 687 1201
Moderate
No No
201 329 501 573 586 942
Moderate
Moderate Moderate Mild Mild Severe Mild Modgate
Moderate Moderate
YeS
No No No No No No No YeS YeS
Moderate Mild
No
Moderate Moderate Moderate
No No
YeS
Table 3: Serum sIL2R levels, inflammatoryactivity and systemic steroid therapy in patients with retinal vasculitis and systemicinflammatory disease sIL-~R (U/ml)
Inflammatory Activity*
851 883 950 1132 3363
Moderate
YeS
Moderate
No
Severe Modaate
No
M&k
YeS
375 420 613 717
Mild Pronounced
Moderate
Yes YeS No
Pronounced
YeS
Demyelination 1 303
Mild
No
CAH 1
Mild
YeS
Patients
Range
Inflammatory Activity*
*see Ref. (8)
Table 1. &2R levels in serum of patients with h n a l vasculitis and Fuchs' hctaochromic cyclitis WtientOroup
sIL-~R (U/ml)
Saraidosis 1 2 3 4
5
% 1 2 3 4
1244
*see Ref. (8), CAH:chronic active hepatitis
Systemic Steroids
YeS
Curr Eye Res Downloaded from informahealthcare.com by North Carolina State University on 10/30/14 For personal use only.
Current Eye Research intraocular inflammation did not appear to influence sIL-2R levels. It is known that sIL-2R levels are raised in immune mediated states and may reflect the intensity of the response (2) and the extent of the disease (3). It Seems clear that sarcoidosis, as an immune mediated systemic disease, is likely to have raised sIL2R. As others have shown the asssociation between sIL-2R levels and disease activity (2,3) it is possible that these receptors could be used to monitor the activity of sarcoidosis and hence its response to treatment. So far, clinical features are the only measure of disease activity. Though important, they tend to reflect gross and often late changes in the disease process. The finding of raised sIL-2R levels in FHC is unexpected but confirms the previous work of Amcker-Mettinger et al. (3, (although Rosenbaum et al. (4) found normal levels in 2 patients in their study). The significance of this is not known but gives further evidence to the theory of immune dysregulation in this condition. It suggests that disease purely localised to the eye can give rise to systemic (peripheral blood) abnormalities. A similar situation has been previously documented, when activated T cells were found in the peripheral blood of some patients with idi-c uveitis (12). This implies that the interpretation of a negative test as a indicator for systemic disease in uveitis patients may indicate that the test was inappropriate or the disease was not present, rather than the eye (asa small organ) having a limited impact on the rest of the body. The wide variation in sIL-2R levels is a feature of this study. For example, whilst there was no overall difference between the values of controls and the RV group, the spread of values in the disease group is so wide (RV 201-1201, controls 276-792 U/ml) that some of the cases must be regarded as having abnormally high levels. Perhaps more emphasis should be placed on the disease activity rather than the actual diagnosis when assessing the results of this test. As sIL-2R levels reflect activity of the immune state rather than inflammation per se,it can be anticipated that there will be, on occasions, a disparity between the clinical findings and sIL-2R levels. If there is a strong association between raised sIL-2R levels and subsequent inflammatory damage then these levels could be used as a guide to the initiation and monitoring of mtxnent. In FHC, where the grumbling inflammation causes visual loss in the form of cataract (which is readily treatable), there is little reason to instigate more aggressive treatment modalities. However, there may be a stronger case for sarcoidosis especially if sIL-2R levels could be shown to predict relapses of inflammation.
Despite the small numbers of patients in this study, ntinal vasculitis in association with SafCOidOSiS is a particular subgroup that may wanant further investigatim on a longitudinal basis. FHC remains an enigma, and futurc rcscaxh in this department is aimed at trying to unravel the mysteries of this condition. ACKNOWLEDGEME"
We are grateful to Helen Jones for statistical assistance.
CORRESPONDINGAUTHOR Philip I. Murray, Ac;sdemic Unit of Ophthalmology, Birmingham and Midland Eye Hospital,Church Street, Birmingham B3 2NS,UK. REFERENCES 1. Rubin, L.A. and Nelson, D.L. (1990) The soluble interleukin-2 receptor: biology, function, and clinical application. AM. Intern. Med. U,6 19-627. 2 . Symons, J.A., Wood, N.C., Di Giovine, F.S. and Duff, G.W. (1988) Soluble IL-2 receptor in rheumatoid arthritis. Correlation with disease activity, IL-1 and IL-2 inhibition. J. Immunol. 141,2612-2618. 3. Manoussakis, M.N., Papado ulos, G.K., Drosos, A.A. and Moutsopoulos, H.M. (19& Soluble interleukin 2 receptor molecules in the serum of patients with autoimmune diseases. Clin. Immunol. Immunopathol. N, 32 1-332. 4. Rosenbaum, J.T., Tilden, M . E and W e , A. (1990) Soluble interleukin-2 levels in patients with uveitis. In 'Ocular Immunology Today', (Eds. Usui, M.,Ohno, S. and Aoki, K.). Pp. 77-80, Excerpta Med~ca,Amsterdam. 5 . Arocker-Mettinger, E, Asenbauer, T., Ulbrich, S. and Grabner, G. (1990) Serum interleukin 2-receptor levels in uveitis. Curr. Eye Res. 9 , 2 5 - 2 9 . 6. Akoglu, T.F., Direskeneli, H., Yazici, H.and Lawrence, R. (1990) TNF, soluble IL-2R and soluble CD-8 in Behget's disease. J. Rheumatol. l7, 1107-1 108. 7. BenD., l3arak, V.,Kalichman, I. and Maftzir, G. (1991) Interleukin-2 receptor in Behst's disease - effect of cyclosporin A. Invest. Ophthalmol. Vis. Sci. 32, 935. 8. Dumonde, D.C., KaspGrochowska, E., Graham,E, Sanders, M.D., Faure, J-P., de Kozak, Y.and van Tuyen, V. (1982) Anti-retinal autoimmunity and circulating immune complexes in patients with retinal vasculitis. Lancet, ii,787-792. 9. Murray, P. (1986) Serum autoantibodies and uveitis. Br. J. Ophthalmol. Zn, 266-268. 10. Murray, P.I., Hoekzema, R., van Haren, M.A.C., de Hon, F.D. and Kijlstra, A. (1990) Aqueous humor interleukin-6 levels in uveitis. Invest. Ophthalmol. Vis. 917-920. Sci. 11. Murray, P.I., Hoekzema, R., Luyendijk, L, Konings, S. and Kijlstra, A. (1990) Analysis of aqueous humor immunoglobulin G in uveitis by enzyme-linked immunombent assay, isoelectric focusing and immunoblotting. Invest. Ophthalmol. Vis. Sci. 2129-2135. 12. Deschenes, J., Char, D.H. and Kaleta, S. (1988) Activated T lymphocytes in uveitis. Br. J. Ophthalmol. 22, 83-87. ~~~
a,
a,
195
