Treatment with C1-inhibitor concentrate does not induce IgM type anti-C1 inhibitor antibodies in patients with hereditary angioedema.
BACKGROUND
Earlier, we found a higher frequency of IgM type C1-inhibitor autoantibodies (C1INH-Abs) in hereditary angioedema (HAE) patients, regardless of previous treatment with C1INH concentrate. The presence of C1INH-Abs correlated with disease severity in patients who have never been treated with C1INH concentrate. We revisited these topics by analyzing a larger patient population with a longer follow-up.


METHODS
We tested IgM type C1INH-Abs (defined as 2 SD higher, than the mean of control, >5.1 AU/ml) in 1127 sera from 130 HAE patients followed up for 8.67 ± 3.18 years. Most analysis was done in a subset of 75 patients, with a follow-up of 9-11 years.


RESULTS
IgM C1INH-Abs were found in 178 sera from 69/130 patients and in 51/75 patients followed up on the long term. Twenty-three/75 (31%) patients had IgM type antibodies in more than 3 serum samples. Temporal changes in the titers of IgM type C1INH Abs followed different patterns. The occurrence of IgM type Abs clustered in some families; there was a highly significant (p = 0.0084) heterogeneity in the levels of IgM C1-INH Abs among the 10 families with at least 3 members. We did not find any significant difference between the frequency of IgM type anti-C1INH antibodies in patients who have never received (n = 15) and in those ever treated (n = 60) with C1INH concentrate. Similarly, no significant correlation was found between the mean dose (number of ampoules) of C1INH concentrate and the frequencies of the levels of IgM type C1INH-Abs. At variance with previous data, the frequency of C1INH-Abs did not correlate either with annual attack rate or with other indicators of the severe course of the disease.


CONCLUSIONS
This study confirmed that the occurrence of IgM type C1INH-Abs in HAE is not related to previous treatment of attacks with C1-inhibitor concentrate. Familial clustering suggests underlying genetic factors presumably unrelated to HAE.
3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi Str 4, H-1125 Budapest, Hungary.
Lilian
L
Varga
George
G
Füst
Dorottya
D
Csuka
Henriette
H
Farkas
D000293:Adolescent; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D050718:Complement C1 Inhibitor Protein / Q000276:immunology* / Q000627:therapeutic use*; D005190:Family; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
D001323:Autoantibodies; D050718:Complement C1 Inhibitor Protein; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M