Association of mannose-binding lectin gene polymorphism but not of mannose-binding serine protease-2 with chronic severe aortic regurgitation of rheumatic etiology

Heart Institute (InCor), University of Sao Paulo School of Medicine, Sao Paulo, Brazil; Institute for Investigation in Immunology, Millennium Institutes, Brazil; Clinical Immunology and Allergy Department, University of Sao Paulo School of Medicine, Sao Paulo, Brazil; Department of Clinical Pathology, Clinical Hospital, Federal University of Paraná, Brazil

^* To whom correspondence should be addressed. Email: ramasawm{at}usp.br.

	Abstract

Background – N-acetylglucosamine (GlcNAc) is the major immunoepitope of group A streptococcal cell wall carbohydrates. Anti-streptococcal antibodies cross-reactive with anti-GlcNAc and laminin are present in sera of patients with rheumatic fever. The cross-reactivity of these antibodies with human heart valvular endothelium and the underlying basement membrane has been suggested to be a possible cause of immune-mediated valve lesion. Mannose-binding lectin (MBL) encoded by the MBL2 gene, a soluble pathogen recognition receptor, has high affinity for GlcNAC. We postulated that mutations in the exon I of MBL2 gene associated with deficient serum level of MBL may contribute to chronic severe aortic regurgitation (AR) of rheumatic etiology.

Methods – We studied 90 patients with severe chronic AR of rheumatic etiology and 281 healthy controls (HC) for the variants of MBL2 gene at codon 52, 54 and 57 by a PCR-RFLP based method.

Results –We observed a significant difference in the prevalence of deficient MBL2 alleles between patients with chronic severe AR and HC. 16% of patients with chronic severe AR were homozygote or compound heterozygote for deficient MBL alleles in contrast to 5% for HC (P=0.0022; OR=3.5 [95%CI 1.6 – 7.7]). No association was detected with the variant of the MASP2 gene.

Conclusion –Our study suggests that MBL deficiency may contribute to the development of chronic severe AR of rheumatic etiology.