Your Genes can protect you from MS


Bettencourt A, Carvalho C, Leal B, Brás S, Lopes D, Martins da Silva A, Santos E, Torres T, Almeida I, Farinha F, Barbosa P, Marinho A, Selores M, Correia J, Vasconcelos C, Costa PP, da Silva BM. The Protective Role of HLA-DRB1(∗)13 in Autoimmune Diseases.J Immunol Res. 2015;2015:948723.

Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB1(∗)15 (OR = 2.17) and HLA-DRB1(∗)03 (OR = 1.81) alleles with MS, HLA-DRB1(∗)03 with SLE (OR = 2.49), HLA-DRB1(∗)01 (OR = 1.79) and HLA-DRB1(∗)04 (OR = 2.81) with RA, HLA-DRB1(∗)07 with Ps + PsA (OR = 1.79), HLA-DRB1(∗)01 (OR = 2.28) and HLA-DRB1(∗)08 (OR = 3.01) with SSc, and HLA-DRB1(∗)03 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB1(∗)13 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB1(∗)13 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB1(∗)13, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB1(∗)13 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.

When I was is Boston I visited the Harvard MS group and saw one of the bags for screening that could be done and was very impressed by the range of assays. One of the assays was to test for the HLA-DR type. We know that HLA-DR2 (serotype) or HLA-DRB1*1501 (geneotype) is the major susceptibility allele for MS. I bet we at Barts don’t do this as a regular check.

How is a T cell stimulated.

This study shows that HLA-DR13 is unrepresented in MS and it looks like people with DR13 delete self reactive cells.

So I say hurray, because I am HLA-DR7 and HLA-DR13. I know this because I donated my blood for experiments and I was found not to respond to myelin oligodendrocyte glycoprotein. Is this why I have ot got MS yet? 

However MD2 is HLA-DR3 and HLA-DR4 and this is the major, major risk factor for type 1 diabetes and rheumatoid arthritis. 

However as MD2 hasn’t got either of these things yet, it shows you that having MS risk genes does not mean you will get MS. Likewise just because you have MS, does not mean that our children will get MS.

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