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MULTICENTRE
STUDIES
GENETICS OF APS:
THE FCγRIIA POLYMORPHISM AND BEYOND
COORDINATORS
Jan Damoiseaux1,
Ruud Theunissen1, José Manuel Matoso Ferreira2, Marta
Baleva3, Milena Nikolova4, Pieter van Paassen1,
and Jan Willem Cohen Tervaert1
1Dept of Clinical and Experimental Immunology, University Hospital
Maastricht, The Netherlands, 2Dept of Internal Medicine, Hospital de
Reynaldo dos Santos, Vila Franca de Xira, Portugal, 3Laboratory of
Clinical Immunology and 4Clinic of Nephrology, University Alexander
Hospital, Sofia, Bulgaria.
PROJECT
At the third European Forum on Antiphospholipid Antibodies participants
were invited to collaborate in a study on the possible association between the
FcγRIIa polymorphism (H131 vs R131) and the APS.
Since in particular IgG2 antiphospholipid antibodies have appeared to be of
clinical relevance, we hypothesized that the presence of the high affinity IgG2
receptor (H131-isoform) enables a cellular contribution to the pathogenesis of
the APS. Furthermore, since the low affinity IgG2 receptor (R131-isoform)
predominates in patients with SLE, the analysis of the FcgRIIa polymorphism in
patients with APS should include a clear distinction between primary and
secondary APS.
Since participation in this study was very limited, only 69 APS patients
and 54 matched controls were included. Although no differences were observed
between APS patients and healthy controls, or between primary and secondary APS
patients, definite conclusions can not be drawn because of the small study
population. In the meantime a meta-analysis on this subject was published by
Karassa et al (Arthritis Rheum
2003). This study revealed enrichment of the RR-genotype in APS, driven mostly by patients with secondary
APS. Furthermore, HH-homozygosity
also tended to predominate in primary APS as compared with secondary APS. These
data support our hypothesis as described above.
To continue our project we propose to extend this genetic study beyond
the FcγRIIa polymorphism and include several other
genetic polymorphisms that have been described to be associated with autoimmune
diseases. Interesting candidate genes include CTLA-4 and PDCD1,
genes encoding for costimulatory molecules that are involved in down-regulation
of the immune response. Polymorphisms in these genes have already been
associated with SLE, but not with APS. Given the association of APS and
infections also genetic polymorphisms in the family of Toll-like receptors will
be of interest. Further suggestions on interesting genetic polymorphisms to be
analysed are welcome.
For additional
information and applications, please e-mail: jdam@limm.azm.nl
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Last updated: 17 November 2005 |
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