AUTOIMMUNITY TO TROPOMYOSIN ISOFORMS IN ULCERATIVE-COLITIS (UC) PATIENTS AND UNAFFECTED RELATIVES

Autoimmunity to cytoskeletal protein tropomyosin (TM) has been demonst rated in UC. However. the TM isoforms involved in this IgG-mediated au toimmune response in UC and the possible presence of serum IgG antibod ies against TM (hTMs IgG) in unaffected UC relatives are unknown. The aim of this study was to investigate the human TM (hTM) isoforms recog nized by serum IgG from UC and to explore whether hTM IgG antibodies a re present in healthy UC relatives. We studied 33 UC patients with 58 unaffected relatives, 31 Crohn's disease (CD) patients with 31 unaffec ted relatives and 20 controls (C). Serum IgG against four recombinant hTM isoforms (hTM1, 2, 3, 5) were tested by ELISA. p-ANCA were tested by ELISA and immunofluorescence. Serum hTM1 and hTM5 Ige were higher i n UC patients than in CD and C (P < 0.005). Among UC patients 52% were seropositive for hTM1 and 64% for hTM5 (P<0.001 versus CD and C). In UC, hTM5 IgG were higher in p-ANCA(+) than in ANCA(-) patients (P=0.04 ). In UC relatives hTM1 IgG were higher than in CD relatives and C (P < 0.01). UC relatives were more frequently seropositive for hTM1 than hTM5 IgG (P = 0.001), while probands were more frequently seropositive for hTM5 IgG (P = 0.008). We conclude that autoimmunity to hTM1 and h TM5 is a feature of UC, while hTM1 IgG differentiate UC relatives from controls. A genetic susceptibility to immune recognition of hTM isofo rms in UC is suggested.