Diagnosis, prevention and treatment of ulcerative colitis,...

A - Human Necessities – 61 – K

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A61K 39/00 (2006.01) A61M 1/38 (2006.01) G01N 33/564 (2006.01)

Patent

CA 2251058

The present invention provides a method of diagnosing ulcerative colitis (UC) in a subject suspected of having inflammatory bowel disease by obtaining a sample from the individual; contacting the sample with human histone H1, or pANCA-reactive fragment thereof, under conditions suitable to form a complex of human histone H1, or pANCA- reactive fragment thereof, and antibody to human histone H1; and detecting the presence or absence of the complex, where the presence of the complex indicates that the individual has UC. The invention also provides related methods of diagnosing a perinuclear anti- neutrophil cytoplasmic antibody positive (pANCA-positive) clinical subtype of UC in a patient with UC. In addition, the invention further provides methods of determining susceptibility to UC in an individual. The invention further provides methods of inducing tolerance in a pANCA- positive patient with UC by administering an effective dose of histone H1, or tolerogenic fragment thereof, to the pANCA-positive patient with UC. Compositions of histone H1, or fragment thereof, combined with a tolerogizing molecule also are provided.

Procédé permettant de diagnostiquer la rectocolite hémorragique (RH) chez un sujet dont on soupçonne qu'il est atteint d'affection intestinale inflammatoire, qui consiste à prélever un échantillon chez ledit sujet, à mettre en contact cet échantillon avec de l'histone H1 humaine ou un fragment à réactivité à pANCA de ladite substance, dans des conditions appropriées à la formation d'un complexe d'histone H1 humaine ou de fragment à réactivité pANCA de ladite substance et d'anticorps contre l'histone H1 humaine et à détecter la présence ou l'absence dudit complexe. La présence de ce complexe indique que le sujet est atteint de RH. La présente invention concerne également des procédés de diagnostic d'un sous-type clinique périnucléaire, antineutrophile, cytoplasmique et positif aux anticorps (pANCA positif) de RH chez un patient souffrant de RH. Elle concerne en outre des précédés permettant de déterminer la susceptibilité à la RH d'un sujet, ainsi que des procédés permettant d'induire la tolérance chez un patient pANCA positif atteint de RH, qui consistent à administrer une dose efficace d'histone H1, ou de fragment tolérogène de ladite substance, à ce patient pANCA positif atteint de RH. Elle concerne encore des compositions d'histone H1, ou de fragments de ladite substance, combinés à une molécule tolérogène.

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