Specific HLA-DRB1 Alleles Associate With Anti-Caspr1 and Anti-CNTN1 Autoantibodies in Autoimmune Nodopathies.
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Lleixà Cinta, Pascual-Goñi Elba, Martín-Aguilar Lorena, Caballero-Ávila Marta, Collet-Vidiella Roger, Tejada-Illa Clara, Llarch Paula, Gallardo Eduard, Boera-Carnicero Gemma, Calahorro Verónica, Callegari Ilaria, Cortese Andrea, Delmont Emilien, Devaux Jerome, Giannotta Claudia C, Nobile-Orazio Eduardo, Höftberger Romana, Sellner Johann, Herdewyn Sarah Andrée Annie J, Alejandra Carvajal, Torné Laura, Jericó Ivonne, Rinaldi Simon, Sommer Claudia, Doppler Kathrin, Armangue Thais, Titulaer Maarten J, Jacobs Bart C, Huizinga Ruth, Wanschitz Julia V, Ortiz Castellon Nicolau, Sparasci Davide, Ripellino Paolo, Pérez-Pérez Helena, Horga Alejandro, Alonso-Jiménez Alicia, De Winter Jonathan, Jauregui Amaia, de la Calle-Martin Oscar, Martinez-Martinez Laura, Querol Luis
Аннотация
METHODS: Forty-four AN patients and 50 seronegative CIDP patients from 19 different European hospitals were included in the study. Thirty AN patients had anti-contactin 1 (CNTN1) antibodies, 11 anti-contactin-associated protein 1 (Caspr1) antibodies, and 3 had antibodies against both proteins. HLA-DRB1 was genotyped at the 4-digit allele levels, and the percentage of individuals carrying each allele was compared with that of the general population, obtained from the Allele frequencies database.
RESULTS: HLA-DRB1*11 alleles appeared in higher proportions in anti-CNTN1+ patients than in seronegative CIDP patients and in the general population (46.7% vs 18% vs 28.4%), with an odds ratio of 3.99 (CI = 1.44 to 11.03, p = 0.01) and 2.2 (CI = 1.07 to 4.53, p = 0.04), respectively. HLA-DRB1*03:01 alleles appeared in significantly higher proportions in anti-Caspr1+ patients than in CIDP patients and in the general population (64.3% vs 22% vs 24.2%), with an odds ratio of 6.38 (CI = 1.77 to 22.99, p = 0.007) and 5.64 (CI = 1.876 to 16.96, p = 0.002), respectively. In the anti-Caspr1+ group, we included 3 patients presenting with antibodies against both CNTN1 and Caspr1 proteins in the acute phase, in which the anti-CNTN1 antibodies disappeared in the chronic phase.
DISCUSSION: HLA-DRB1*11 alleles are associated with the detection of anti-CNTN1 antibodies in AN patients, and HLA-DRB1*03:01 alleles associate with anti-Caspr1 antibodies. In addition, our study suggests that antiparanodal antibodies targeting both Caspr1 and CNTN1 are present in a small number of patients with AN. These data reinforce the idea that these patients represent specific subsets with clinical features and risk factors that differ from seronegative CIDP patients and from other AN patients. However, further studies should address the functional relevance of these associations and their pathophysiologic implications.