Sandrine Guis

Transfer of the shared epitope through microchimerism in women with rheumatoid arthritis.

OBJECTIVEnRheumatoid arthritis (RA) is an autoimmune disease that affects mostly women and is associated with HLA-DRB1 genes having in common a shared epitope sequence. In parallel, cells and/or DNA originating from pregnancy (microchimerism) persist for decades and could contribute to autoimmunity. The aim of this study was to examine whether microchimerism may be a source of the shared epitope among women with RA.nnnMETHODSnWomen with RA and healthy women who lacked RA-associated genes such as HLA-DRB1*01 (n=33 and n=46, respectively) and/or HLA-DRB1*04 (n=48 and n=64, respectively), were tested for DRB1*01 or DRB1*04 microchimerism by HLA-specific quantitative polymerase chain reaction assays. As controls, alleles not associated with RA (DQB1*02 and DRB1*15/16) were also analyzed.nnnRESULTSnCompared with healthy women, women (42% with RA had a higher frequency and higher levels of DRB1*04 microchimerism versus 8%; P=0.00002) as well as DRB1*01 microchimerism (30% versus 4%; P=0.0015). Moreover, no difference in microchimerism was observed for alleles not associated with RA.nnnCONCLUSIONnWomen with RA had microchimerism with RA-associated HLA alleles, but not with non-RA-associated HLA alleles, more often and at higher levels compared with healthy women. These observations are the first to indicate that microchimerism can contribute to the risk of an autoimmune disease by providing HLA susceptibility alleles.

Segmentation of fascias, fat and muscle from magnetic resonance images in humans: the DISPIMAG software.

Segmentation of human limb MR images into muscle, fat and fascias remains a cumbersome task. We have developed a new software (DISPIMAG) that allows automatic and highly reproducible segmentation of lower-limb MR images. Based on a pixel intensity analysis, this software does not need any previous mathematical or statistical assumptions. It displays a histogram with two main signals corresponding to fat and muscle, and permits an accurate quantification of their relative spatial distribution. To allow a systematic discrimination between muscle and fat in any subject, fixed boundaries were first determined manually in a group of 24 patients. Secondly, an entirely automatic process using these boundaries was tested by three operators on four patients and compared to the manual approach, showing a high concordance.

HLA DRB1, DMA, and DMB gene polymorphisms in Rheumatoid Arthritis

OBJECTIVEnTo study the influence of DMA and DMB genes on susceptibility to Rheumatoid Arthritis (RA).nnnMETHODSnHLA-DRB1, DMA and DMB polymorphisms were defined by PCR SSOP in 203 European Mediterranean RA patients and 181 unrelated healthy controls.nnnRESULTSnNo significant difference in the phenotype frequencies of DMA and DMB alleles was observed between patients and controls. We found decreased frequencies of DMA*0102 and DMB*0104 in patients but this did not reach significance. These decreased frequencies could be due to a positive linkage disequilibrium with DRB1*0701, an allele which is underrepresented in RA patients. In stratified analysis with RA susceptibility Epitope positive (SE) DRB1 alleles, there was no significant difference in DMA and DMB phenotype frequencies between SE/SE, SE/X, and X/X patients versus controls. Among SE/X subjects, no significant difference in DM distribution frequencies was observed in DRB1*0101/X, 0102/X, 0401/X, 0404/X and 0405/X groups.nnnCONCLUSIONnDMA and DMB polymorphism does not seem to influence susceptibility to develop RA. Differences in DMA phenotype frequencies between patients and controls are secondary to linkage disequilibrium with DRB1 alleles.

Maladie de von Recklinghausen et lombosciatique: à propos d'un cas

s / Revue du Rhumatisme 73 (2006) 1089–1259 1106

The shared epitope revisited: shared epitope negative HLA-DR alleles influence susceptibility to rheumatoid arthritis

We propose to classify HLA-DRB1 alleles into 3 groups: shared epitope positive (SE), shared epitope negative with a positively charged HLA-DR P4 pocket (XP4p) and shared epitope negative with a negative or neutral HLA-DR XP4 pocket (XP4n). Using this classification to analyse 3 different French populations, we find that: n n-SE/SE or SE/XP4p genotypes are associated with a high risk to develop RA. n n-XP4p/XP4p or SE/XP4n genotypes are neutral n n-XP4p/XP4p or XP4n/XP4n genotypes are protective with respect to the development of RA.

In Marseille, Southern France, HLA-B2702 carries higher risk than HLA-B2705 to develop ankylosing spondylitis (AS)

HLA-B27 subtypes were defined by molecular typing in 45 patients with AS and 90 controls from Marseille. We subdivided patients and controls in 2 subgroups, according to the birth place of their grandparents: 19 patients and 38 controls constituted the Spanish/North African subgroup; 26 patients and 52 controls constituted the French subgroup. In patients from the Spanish/North African subgroup, the frequency of B2702 was higher (74%) than in controls from the same area (21%)pc<0.01 and the frequency of B2705 was lower in patients (25%) than in controls (79%) pc<0.01. In patients from the French group, the frequency of B2702 was higher (7%) than in controls (2%)(N.S.). n nThus, in the population of Southern France, B2702 seems to carry higher risk to develop AS than B2705.