title: C1-inhibitor (C1-INH) autoantibodies in hereditary angioedema. Strong correlation with the severity of disease in C1-INH concentrate naïve patients.
abstract: The presence of autoantibodies to C1-inhibitor (C1-INH-Abs) is a hallmark of acquired C1-inhibitor deficiency. However, only scarce data are available on their prevalence in hereditary angioedema (HAE). In a prospective study performed between 2001 and 2004 in 95 patients with Type I or II HAE, serum samples were taken one to three times a year and clinical status of the patients was registered. Serum samples were tested for total activity of the classical pathway, C1q, C3, C4 and C1-inhibitor (C1-INH) concentration and activity levels, as well as the presence of IgG, IgA and IgM type anti-C1-inhibitor antibodies (C1-INH-Ab). Fifty-four healthy age and gender matched persons served as control. Significant differences between the patients and controls in the occurrence of elevated (2S.D. higher than mean of control) C1-INH-Abs titers was found only in the case of IgM type C1-INH-Abs. Elevated (>4.22AU/ml) IgM C1-INH-Abs levels were found in 31 and 4% of the patients and controls, respectively (p<0.001). Surprisingly, high titer IgM C1-INH-Abs were present with equal frequency in the 41 HAE patients ever treated with C1-INH concentrate and in the 54 C1-INH treatment naïve patients. In the latter group, strong positive correlation between the levels of the IgM C1-INH-Abs and the most severe disease (score 1) (p=0.0021) and the yearly attack rate (p=0.0173) were obtained. In addition, the levels of the IgM C1-INH-Abs exhibited strong negative correlation to the C1-inhibitor concentration and functional activity, total classical complement pathway activity, and a positive correlation to total IgM concentration. Taken together, these data indicate that IgM type C1-INH-Abs are present with highly elevated frequency in HAE patients irrespectively of the previous treatment with C1-INH concentrate. Most probable production of these autoantibodies is the consequence of the activation of complement and other plasma enzyme systems during HAE attacks. Determination of IgM C1-INH-Abs can be used as an activity marker in HAE.
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi 4, H-1125 Budapest, Hungary.
authors.forename: Lilian
authors.initials: L
authors.lastname: Varga
authors.forename: Gábor
authors.initials: G
authors.lastname: Széplaki
authors.forename: Beáta
authors.initials: B
authors.lastname: Visy
authors.forename: George
authors.initials: G
authors.lastname: Füst
authors.forename: George
authors.initials: G
authors.lastname: Harmat
authors.forename: Katalin
authors.initials: K
authors.lastname: Miklós
authors.forename: Julianna
authors.initials: J
authors.lastname: Németh
authors.forename: László
authors.initials: L
authors.lastname: Cervenak
authors.forename: István
authors.initials: I
authors.lastname: Karádi
authors.forename: Henriette
authors.initials: H
authors.lastname: Farkas
mesh_terms: D000293:Adolescent; D000328:Adult; D000799:Angioedema / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D050718:Complement C1 Inhibitor Protein / Q000276:immunology*; D005260:Female; D006801:Humans; D007114:Immunization; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D050718:Complement C1 Inhibitor Protein; D007075:Immunoglobulin M