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ARTICLES
Year : 1979  |  Volume : 27  |  Issue : 4  |  Page : 53-55

Cross reactivity of antilens antibody with extra and intraocular tissues


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R N Misra
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India
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How to cite this article:
Misra R N, Rahi A. Cross reactivity of antilens antibody with extra and intraocular tissues. Indian J Ophthalmol 1979;27:53-5

How to cite this URL:
Misra R N, Rahi A. Cross reactivity of antilens antibody with extra and intraocular tissues. Indian J Ophthalmol [serial online] 1979 [cited 2020 Aug 13];27:53-5. Available from: http://www.ijo.in/text.asp?1979/27/4/53/32575

Interest in the antigenicity of the mammalian lens and its role in the production of auto­immune lesion (lens induced uveitis) in the eye appears to have originated with the study of Uhlenhuth[11], which led to the general conclusion that the lens antigens were largely organ specific. This view prevailed for several decades among experimental ophthalmologists. Contrary to basic concept of organ specificity of the lens antigens, it was also observed that protein resembling those found in the lens are seen not only in other ocular tissues but also in almost every organ of the body [2],[4] to[8]; leading to the conclusion that, lens antigens are neither tissue nor species specific. The rational explanation and microscopical localisation of these cross reacting antigen, lens protein will be reported in this paper.


  Materials and methods Top


The experiments were performed in the institute of ophthalmology, London on healthy New Zealand albino adult rabbits, litter mates being used when ever possible. Heterologous lens from guineapig and rats, homologous lens and autologous lens from rabbit in saline or with incomplete and complete Freuds adjuvant were injected separately in different groups of rabbits.

The injections were given intramuscularly at different sites at 10 day intervals. The animals were bled on the day of initial immunisation and also at the time of subsequent injections in order to study the sequential antibody response. The sera were deep frozen and stored and tested for cross reactivity. The antibodies were tested by agar gel diffusion, immuneelectropho­resis, haemagglutination, immunofluorescence and immuno per oxidase test. The cross reaction of antilens antibody with different intra and extra ocular tissues were observed by gel diffusion, immunofluorescence and immuno-peroxidase method. The details of the methods and study have been mentioned elsewhere[7],[4] I,II;


  Results Top


In the animals where heterologous lens was injected, the potent lens antisera showed the cross reaction with iris, liver, kidney and spleen, as shown by agar gel diffusion. The immuno­fluorescene and immuno peroxidase tests showed that antilens sera reacted strongly with lens epithelium and cortex. In addition, positive reaction was seen with the iris, the ciliary body, the corneal epithelium and the inner retina. Diffuse as well as coarse granular reactions were noted with gastric parietal cells and chief cells, hepatocytes, and renal tubular epithelium suggesting the presence of antimito­chondrial and antiribosomal antibodies in lens antisera. Moreover, some of the stronger antisera reacted with skeletal muscles in the rat diaphragm and smooth muscle fibre in rat stomach and glomeruli suggesting the presence of antibodies to contractile proteins. Some of the antisera also contained weak antinuclear antibodies.

The rabbit lens antisera raised against the homologous lens showed the weak cross reac­tivity with the iris, the ciliary body, the corneal epithelium and the retina. Diffuse as well as coarse granular reactions were also noted with gastric parietal and chief cells, hepatocytes and renal tubular epithelium. This suggests the presence of antimitochondrial, antiribosomal antibodies in homologous lens antisera. A strong antiserum from one animal reacted with smooth muscle fibres in rat stomach, suggesting the presence of antibodies to contractile muscle proteins.

The autologous rabbit lens antisera showed by immunofluorescence and immuno peroxidase the strong reaction with the lens epithelium and and the outer cortex. In addition, sera with high lens haemagglutinin titre showed cross reactivity with the iris and the corneal epithe­lium. A similar cross reactivity, although of relatively weak nature, was also observed with extraocular tissue as described for heterologous and homologous antilens antisera.


  Discussion Top


The cross reactivity of heterologous lens antisera with intraocular and extraocular tissues have been demonstrated by various investigators as mentioned earlier. By using sophisticated technique like immunofluorescence and immuno peroxidase we showed the cross reactivity of homologous lens antisera with extra and intra­ocular tissues. In the same way we demonstra­ted the cross reactivity of autologous lens antisera with intra and extraocular tissues first time by immunofluorescene and immuno-per­oxidase techniques.

Our study of cross reactivity has shown for the first time, the potent lens antisera contain antibodies to mitochondria, ribosomes, contrac­tile proteins, and cell nuclei. By means of differential centrifugation and equilibrium cent­rifugation in density gradients it has been shown that antibodies which react with the chief cells of stomach, the hepatocytes, and the renal tubular epithelium to give diffuse fluorescence are antiribosomal antibodies, whereas those which react with gastric parietal cells, hepatocy­tes and tubular epithelium to give a rather granular fluorescence are antimitochondrial anti­bodies.[10],[1],[12] It is of interest that both these anti­bodies are non species and non organ specific. It is now known that antibodies to contractile proteins such as myosin and actin, which are common in autoimmune disorders including uveitis, react well with smooth muscle fibres in the rat stomach, the blood vessels, and the glomeruli[8]. A similar fluorescence observed antilens sera clearly shows that these sera con­tain antibodies to cell mitochondria, smooth muscle contractile proteins, and ribosomes.

The modern concept that lens antigens which were once believed to be organ specific, are neither tissue nor species specific, is compatible with the finding presented in this paper. It provides for the first time, a rational explana­tion, at least in part, for the cross- reactivity of antilens sera. Almost every tissue in the body contains mitochondria, endoplasmic reticulum, nuclei and contractile filaments and would be expected to cross react with potent antisera produced against the lens homogenates which for developmental reasons contain all these structures entrapped among the specific lens crystallins.


  Summary Top


The rabbits were immunised by hetero, homo and by autologous antigens. The antilens anti­bodies were demonstrated by agar gel diffusion, immunoelectrophoresis, haemagglutination, immunoflourescence and immunoperoxidase techniques. It has been demonstrated that potent antilens sera contains antibodies to mitochondria, ribosomes, contractile proteins and the cell nuclei.

This work provides, for the first time, a rational explanation for the widly observed phenomenon of cross reactivity of antilens sera with various intra and extra ocular tissues of animal body and forward a hypothesis that lens antigens are neither organ nor species specific.

 
  References Top

1.
Anderson, J.R., Buchanan, W.W. and Goudie, R.B., 1967, Autoimmunity, Clinical and experi­mental, Thomas Spring Field, Illinois.  Back to cited text no. 1
    
2.
Bour's, J. and Doorenmaalan, W.J., 1972, Experimental Eye Research, 13, 236.  Back to cited text no. 2
    
3.
Hektoen, L., 1922, Jour of Infectious Disease, 31, 72.  Back to cited text no. 3
    
4.
Misra, R.N., Rahi, A.H.S., Morgan, G, 1977, Brit. J. Ophthat., 61, 285.  Back to cited text no. 4
    
5.
Perkins, E.S. and Wood, R.M., 1963, Experi­mental Eve Research, 2, 255.  Back to cited text no. 5
    
6.
Rahi, A.H.S., Misra, R.N. and Morgan, G. 1977, Brit. J. Ophthal., 61, 164.  Back to cited text no. 6
    
7.
Rahi, A.H.S., Misra, R.N. and Morgan, G., 1977, Brit. J. Ophthal., 61, 371.  Back to cited text no. 7
    
8.
Rahi, A.H.S., Holborow, E.J. Perkins, E.S., Gunger, Y.Y. and Dinning W.J. 1976, Trans. Ophthal. Soc. U.K. 96, 113.  Back to cited text no. 8
    
9.
Rao, S.S., Kulkarnee, M.E., Cooker S.N. and Radhakrishnan M.R., 1955, Brit. J. Ophthal., 39, 163.  Back to cited text no. 9
    
10.
Taylor, K.B., Roitt I.M., Doniah, D., Couchman, K.G. and Shapland, K.C., 1962, Brit. Med. Jour., 2, 1347.  Back to cited text no. 10
    
11.
Uhlenhuth, P.T., 1903, Festschirft zum secbzigs­ten Guberstage von Robert Koch, Fischer Jena.   Back to cited text no. 11
    
12.
Wright, R., 1975, Clinical Aspect of Immuno­logy, 1269, Edited by P.G.H. Gell, R.R.A. Coombs, and, P.J. Lachmann Blhckwell, Oxford.  Back to cited text no. 12
    




 

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