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| Year : 2010 | Volume
: 21
| Issue : 1 | Page : 163 |
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| SLE Conundrums |
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E Nigel Wardle
London NW1 8JS, United Kingdom
Click here for correspondence address and email
| Date of Web Publication | 8-Jan-2010 |
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How to cite this article:
Wardle E N. SLE Conundrums. Saudi J Kidney Dis Transpl 2010;21:163 |
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 | |  |
| 1. | Wardle EN. Systemic lupus erythematosus Conundrums. Saudi J Kidney Dis Transpl 2009 ;20(5):731-6.  |
| 2. | Ramos-Casals M, Soto MJ, Cuadrado MJ, Khamashta MA. Rituximab in systemic lupus erythematosus. Lupus 2009;18(9):767-76 |
| 3. | Mackay F, Schneider P. Cracking the BAFF code. Nat Rev Immunol 2009;9:491-502 [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 [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. [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. [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. [PUBMED] [FULLTEXT] |
Correspondence Address:
E Nigel Wardle
London NW1 8JS
United Kingdom
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PMID: 20061717 
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