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.
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