title: Prognostic value of anti-ADAMTS 13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS 13 activity.
abstract: To study both the pathophysiologic and the prognostic value of ADAMTS13 in thrombotic microangiopathies (TMAs), we enrolled a cohort of 35 adult patients combining a first acute episode of TMA, an undetectable (below 5%) ADAMTS13 activity in plasma, and no clinical background such as sepsis, cancer, HIV, and transplantation. All patients were treated by steroids and plasma exchange, and an 18-month follow-up was scheduled. Remission was obtained in 32 patients (91.4%), and 3 patients died (8.6%) after the first attack. At presentation, ADAMTS13 antigen was decreased in 32 patients (91.4%), an ADAMTS13 inhibitor was detectable in 31 patients (89%), and an anti-ADAMTS13 IgG/IgM/IgA was present in 33 patients (94%). The 3 decedent patients were characterized by the association of several anti-ADAMTS13 Ig isotypes, including very high IgA titers, while mortality was independent of the ADAMTS13 inhibitor titer. In survivors, ADAMTS13 activity in remission increased to levels above 15% in 19 patients (59%) but remained undetectable in 13 patients (41%). Six patients relapsed either once or twice (19%) during the follow-up. High levels of inhibitory anti-ADAMTS13 IgG at presentation were associated with the persistence of an undetectable ADAMTS13 activity in remission, the latter being predictive for relapses within an 18-month delay.
authors.affiliation: Baxter Bioscience, Department of Discovery Research and Technical Assessment, Vienna, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferrari
authors.forename: Friedrich
authors.initials: F
authors.lastname: Scheiflinger
authors.forename: Manfred
authors.initials: M
authors.lastname: Rieger
authors.forename: Geert
authors.initials: G
authors.lastname: Mudde
authors.forename: Martine
authors.initials: M
authors.lastname: Wolf
authors.forename: Paul
authors.initials: P
authors.lastname: Coppo
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Girma
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.forename: Christian
authors.initials: C
authors.lastname: Brun-Buisson
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mira
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: Pascale
authors.initials: P
authors.lastname: Poullin
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schleinitz
authors.forename: Benoit
authors.initials: B
authors.lastname: Schlemmer
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Teboul
authors.forename: Philippe
authors.initials: P
authors.lastname: Vanhille
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vernant
authors.forename: Dominique
authors.initials: D
authors.lastname: Meyer
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000172:deficiency* / Q000276:immunology*; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000743:Anemia, Hemolytic / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005602:France; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000276:immunology; D013927:Thrombosis / Q000097:blood / Q000276:immunology*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D007132:Immunoglobulin Isotypes; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human