Systemic lupus erythematosus and rheumatoid arthritis

0
1
2
3
4
A
C
R 
cr
ite
ria
SL
ICC i
nde
x
SL
ED
A
I (
1)
SL
ED
A
I (
2)
OR
The 
PD1.3A
polymorphism is intronic but has a functional relevance since it 
theoretically disrupts a transcription site for the RUNX-1 transcription factor.
151
Disruption of RUNX-1 binding sites in different genes has been proposed as a 
plausible explanation as to why certain polymorphisms have been associated 
with the autoimmune diseases SLE, RA and with psoriasis.
152; 202
The risk allele 
has been shown to result in decreased transcriptional activity of 
PDCD1
in a 
transfected human T-cell line.
159
Patients homozygous for the 
PD1.3A
allele 
have been shown to have reduced PD-1 expression on activated CD4+ T-
cells.
159
However, there are studies disputing the functional relevance of the 
PD1.3A
allele. Analysis of the 
PDCD1
gene expression in population-based B-
cell lines failed to reveal statistical evidence for an altered transcription between 
having or nor having the 
PD1.3
risk allele (unpublished results). Thus, the 
function of the risk allele in B-cells could not be confirmed. In one study, 
disruption of the RUNX-1 binding site was confirmed through electric mobility 
shift assays. However, the loss of binding was not due to the risk allele but 
because of flanking nucleotides that negatively affected RUNX-1 binding.
203
Taken together, the functional results are ambiguous and the 
PD1.3
polymorphism may not be the causative SNP, it may possibly be in LD with 
another, yet unknown, disease causing SNP. Further characterization of the 
functionality is needed in order to confirm the role of the risk allele in terms of 
susceptibility for and severity of SLE.
In summary: The 
PD1.3A
allele was not associated with SLE 
per se
, it was, 
however, highly associated with a renal disorder, which is an established severe 
manifestation in patients with SLE.
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