@article{32147,
  keywords = {leprosy, Complement receptor 1, Pathophysiology, Brazil},
  author = {Kretzschmar GC and Oliveira LC and Nisihara RM and Velavan TP and Stinghen ST and Stahlke E and Petzl-Erler ML and Messias-Reason LJT and Boldt A},
  title = {Complement receptor 1 (CR1, CD35) association with susceptibility to leprosy.},
  abstract = {<p><strong>BACKGROUND: </strong>Pathophysiological mechanisms are still incompletely understood for leprosy, an urgent public health issue in Brazil. Complement receptor 1 (CR1) binds complement fragments C3b/C4b deposited on mycobacteria, mediating its entrance in macrophages. We investigated CR1 polymorphisms, gene expression and soluble CR1 levels in a case-control study with Brazilian leprosy patients, aiming to understand the role of this receptor in differential susceptibility to the disease.</p>

<p><strong>METHODOLOGY: </strong>Nine polymorphisms were haplotyped by multiplex PCR-SSP in 213 leprosy patients (47% multibacillary) and 297 controls. mRNA levels were measured by qPCR and sCR1 by ELISA, in up to 80 samples.</p>

<p><strong>PRINCIPAL FINDINGS: </strong>Individuals with the most common recombinant haplotype harboring rs3849266*T in intron 21 and rs3737002*T in exon 26 (encoding p.1408Met of the York Yka+ antigen), presented twice higher susceptibility to leprosy (OR = 2.43, p = 0.017). Paucibacillary patients with these variants presented lower sCR1 levels, thus reducing the anti-inflammatory response (p = 0.040 and p = 0.046, respectively). Furthermore, the most ancient haplotype increased susceptibility to the multibacillary clinical form (OR = 3.04, p = 0.01) and presented the intronic rs12034383*G allele, which was associated with higher gene expression (p = 0.043), probably increasing internalization of the parasite. Furthermore, there was an inverse correlation between the levels of sCR1 and mannose-binding lectin (initiator molecule of the lectin pathway of complement, recognized by CR1) (R = -0.52, p = 0.007).</p>

<p><strong>CONCLUSIONS: </strong>The results lead us to suggest a regulatory role for CR1 polymorphisms on mRNA and sCR1 levels, with haplotype-specific effects increasing susceptibility to leprosy, probably by enhancing parasite phagocytosis and inflammation.</p>
},
  year = {2018},
  journal = {PLoS neglected tropical diseases},
  volume = {12},
  pages = {e0006705},
  issn = {1935-2735},
  url = {http://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0006705&type=printable},
  doi = {10.1371/journal.pntd.0006705},
  language = {eng},
}