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Saudi Journal of Kidney Diseases and Transplantation
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LETTER TO THE EDITOR Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 1  |  Page : 163
SLE Conundrums


London NW1 8JS, United Kingdom

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Date of Web Publication8-Jan-2010
 

How to cite this article:
Wardle E N. SLE Conundrums. Saudi J Kidney Dis Transpl 2010;21:163

How to cite this URL:
Wardle E N. SLE Conundrums. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Oct 24];21:163. Available from: https://www.sjkdt.org/text.asp?2010/21/1/163/58797
To the Editor,

Although it is only a few months since I wrote my recent article on SLE conundrums, [1] there have already been several articles that relate to the points of understanding. Yet, for a start, nephrologists may have been upset to read in Nature Reviews Nephrology of June 09 (p503) that "Lupus nephritis trials end in disappoint­ment". Well abetimus is abandoned, but induc­tion therapy with Rituximab goes ahead and is generally successful. [2] Rituximab has 90% effi­cacy and adverse effects occur only in 20% of treated persons. If there is relapse, rituximab can be repeated within 1 year. We now have the prospect of anti-BLys/BAFF trials. [3],[4] B­Lys is the cytokine that arises from T cells and dendritic cells (DCs), neutrophils and mono­cytes and is B cell activating Factor that con­tributes to autoantibody production by B lym­phocytes. Its formation is stimulated by IFNy and by IFN-alpha. [4]

I am sure that readers understand that there is hypomethylation of genes in CD4 T cells in SLE, [1] and that this means that some genes are over-expressed and so there can be hypercyto­kinaemia. Demethylation also explains reacti­vation of the inactive X chromosome in the female.

The increased apoptosis of CD4 T cells in SLE has been shown to relate to an apoptosis­related gene BclG-L. [5] So, this is in part expla­nation of uploading of self-antigens for presen­tation to DCs that is an important feature of SLE.

My text drew attention to the fact that we know now from the work of Tsokos that double negative T cells (CD3+, CD4-, CD8-) produce interleukin 17 in mice and in humans. In lupus prone mice there are aberrantly active IL­23→IL-17 cytokines, [6] Hence Th17 lymphocytes arise and they are even found in the kidneys.

All this new understanding begins to fit to­gether. For mind-stretching reading abnorma­lities in 25 genes have been identified! [7]

 
   References Top

1.Wardle EN. Systemic lupus erythematosus Conundrums. Saudi J Kidney Dis Transpl 2009 ;20(5):731-6.  Back to cited text no. 1      
2.Ramos-Casals M, Soto MJ, Cuadrado MJ, Khamashta MA. Rituximab in systemic lupus erythematosus. Lupus 2009;18(9):767-76  Back to cited text no. 2      
3.Mackay F, Schneider P. Cracking the BAFF code. Nat Rev Immunol 2009;9:491-502  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Harigai M, Kawamoto M, Hara M, et al. Excessive production of interferon-gamma in SLE and its contribution to induction of BLys/BAFF. J Immunol 2008;181:2211-9  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Luo N, Wu Y, Chen Y, et al. Upregulated Bcl­GL expression enhances apoptosis of peripheral blood CD4 T lymphocytes in patients with SLE. Clin Immunol 2009;132:349-61.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]  
6.Zhang Z, Kyttaris VC, Tsokos GC. The role of the IL-23/IL17 axis in lupus nephritis. J Immunol 2009;183:3160-9.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]  
7.Moser KL, Kelly JA, Lessard CJ, Harley JB. Recent insights into the genetic basis of systemic lupus erythematosus. Genes Immunity 2009;10: 373-9.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  

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Correspondence Address:
E Nigel Wardle
London NW1 8JS
United Kingdom
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PMID: 20061717

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