Lupus and MECP2

Systemic lupus erythematosus (SLE) CAUTION2is an autoimmune disease that most frequently affects women between the ages of 15 and 35 but can affect both males and females of any age. It can be severe and life-threatening with periods of acute illness and remission.

Recent studies have suggested that the MECP2 gene the neighboring IRAK1 gene play a role in Lupus. These studies suggest that some unusual variations in the structure of the MECP2 gene that result in MeCP2 overactivity increase the risk for lupus. These SNPs (Single Nucleotide Polymorphisms) result in slightly different gene structures that are now associated with higher or lower activity levels.

This research on Lupus may have a number of interesting implications for MECP2 Duplication Syndrome and raise a number of questions:

1. Both MECP2 Duplication Syndrome and Systemic lupus erythematosus affect T-Cells. While MECP2 Duplication Syndrome is generally associated with an underactive immune system and Lupus is generally associated with an overactive system, it may be helpful to assess whether there may be some similar effects. For example, some effects of MECP2 duplication may be the result of inflammation and some individuals have reported that anti-inflammatory drugs have been helpful.

2. It is interesting that MECP2 Duplication Syndrome affects mostly males while Lupus affects mostly females. If the Lupus associated SNPs in MECP2  result in higher levels of the MeCP2 protein, one might expect this to be more extreme among males since they have only one X-chromosome so there can be no balancing from a second X-chromosome without the variant SNP.

3. The fact that some of MECP2 SNPs have been associated with increased protein production provides some support for the idea that varying forms of MECP2 may increase or decrease the severity of the duplications. (see Varying MECP2 Gene Structures and Duplication Severity).

4. Clearly, the apparent role of MECP2 in another serious health condition adds to the the urgency of learning more about this gene and how it works in health and illness. Hopefully, research on Lupus and MECP2 Duplication Syndrome will come together to yield better understanding and treatment of both conditions.

For more on Lupus and MECP2, see:

Alonso-Perez, E., Suarez-Gestal, M., Calaza, M., Ordi-Ros, J., Balada, E., Bijl, M., et al. (2012). Further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study. PLoS One, 7(9), e45356.

Kaufman, K. M., Zhao, J., Kelly, J. A., Hughes, T., Adler, A., Sanchez, E., et al. (2012). Fine mapping of Xq28: both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groups. Ann Rheum Dis, 72(3), 437-444.

Koelsch, K. A., Webb, R., Jeffries, M., Dozmorov, M. G., Frank, M. B., Guthridge, J. M., et al. (2013). Functional characterization of the MECP2/IRAK1 lupus risk haplotype in human T cells and a human MECP2 transgenic mouse. J Autoimmun, 41, 168-174.

Sanchez, E., Comeau, M. E., Freedman, B. I., Kelly, J. A., Kaufman, K. M., Langefeld, C. D., et al. (2011). Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study. Arthritis Rheum, 63(11), 3493-3501.

Sestak, A. L., Furnrohr, B. G., Harley, J. B., Merrill, J. T., & Namjou, B. (2011). The genetics of systemic lupus erythematosus and implications for targeted therapy. Ann Rheum Dis, 70 Suppl 1, i37-43.

Zhou, Y., Qiu, X., Luo, Y., Yuan, J., Li, Y., Zhong, Q., et al. (2011). Histone modifications and methyl-CpG-binding domain protein levels at the TNFSF7 (CD70) promoter in SLE CD4+ T cells. Lupus, 20(13), 1365-1371.


4 responses to “Lupus and MECP2

  1. That is interesting, Dick. I am a duplication carrier and we were tested b/c Liam has the syndrome. My mother (Liam’s maternal grandmother) was not tested but has Lupus. (I am one of her 2 children. I have a typically developing brother.) Dr. Ramocki was very interested when I shared this with her, but it was at the first conference and things were busy, so we didn’t have a chance to talk more.

  2. To clarify – my mother has not been tested as a carrier, but does have Lupus. It is very possible that she is, indeed, a carrier.

    • If there are any other mothers of boys (or girls) with MECP2 Duplication Syndrome who have mothers, sisters, or female cousins on your mother’s side who have had lupus, I would love to hear from you. You can comment here or if you prefer e-mail me privately at

  3. I find this very interesting. I am a carrier of the mecp2 duplication and Alfie my youngest son has mecp2 duplication however I was tested for lupus in my youth because I had chronic joint pain in most major joints and back. Doctors never got to the bottom of it and now at 34 I just have to manage the pain as it occurs. Probably far of the mark but interested to know if any other carrier mothers have had any such problems?

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s