European families reveal MHC class I and II associations with autoimmune-mediated congenital heart block

• Published in: Annals of the rheumatic diseases Vol. 77; no. 9; pp. 1381 - 1382
• Main Authors: Kyriakidis, Nikolaos C, Kockum, Ingrid, Julkunen, Heikki, Hoxha, Ariela, Salomonsson, Stina, Meneghel, Lauro, Ebbing, Cathrine, Dilthey, Alexander, Eronen, Marianne, Carolis, Sara De, Kiserud, Torvid, Ruffatti, Amelia, Kere, Juha, Meisgen, Sabrina, Wahren-Herlenius, Marie
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.09.2018
• Subjects: Autoimmune diseases; Congenital diseases; Congenital heart block; Disease; Families & family life; Haplotypes; Heart; Lymphocytes; Major histocompatibility complex; Medicin och hälsovetenskap; Pathogenesis; Values; Italy; Sweden; Norway; Finland; Autoimmunity; Cardiovascular Disease; Autoantibodies
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2018-212953

Potent cytotoxic responses can be mediated by HLA-C both in the context of NK and CD8+ T cells recognition, but with low level cell surface expression and a more restricted peptide binding, this HLA distinguishes itself among the class I molecules.3 Interestingly, immunohistology of heart tissue of fetuses deceased from CHB shows CD8+ T cells in the mononuclear cell infiltrates,4 indicating a direct role for HLA class I peptide presentation to CD8+ T cells in the disease pathogenesis. There are many reports of negative DRB1*13 associations in European populations with autoimmune diseases.6 We therefore hypothesise that the protective DRB1*13 association with CHB depends on a general mechanism of protection from inflammation shared among autoimmune diseases, and interpret the observed lack of significantly associated HLA alleles that increase susceptibility to CHB as consistent with the fact that the pathogenic CHB-initiating autoantibodies are generated in the mother. Funding The study was supported by grants from the Swedish Research Council, the Heart-Lung Foundation, the Stockholm County Council, Karolinska Institutet, the Swedish Rheumatism Association, the King Gustaf Vth 80-year Foundation and the Freemason’s in Stockholm Foundation for Children’s Welfare.