BF*F allotype of the alternative pathway of complement: A marker of protection against the development of antiphospholipid antibodies in patients with systemic lupus erythematosus

Picceli, Vanessa; Skare, Thelma Larocca; Nisihara, Renato; Nass, Flávia Raphaela; Messias-Reason, Iara; Utiyama, Shirley Ramos da Rosa

doi:10.1177/0961203315615222

Cited by 4 publications

(1 citation statement)

References 31 publications

(36 reference statements)

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“…Besides, this linkage has been turned more complicated during the HLA research course. Early in the study of HLA was described a strong linkage disequilibrium not only among HLA genes of the haplotype HLA-B8-DR3 but between HLA and complement (C2, C4a, C4b, and Factor B) ( Black et al, 1982 ; Wescott et al, 1987 ; Picceli et al, 2016 ). Currently, it is known that a considerable number of variants, mainly of MHC class three, are in linkage disequilibrium with the variants of B and DR indicated above, which increases the genetic risk load of the individual with lupus.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of Genetic Admixture Determines SLE Susceptibility in Mexican

et al. 2021

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Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well identified as risk factors. SLE patients present different clinical phenotypes, which are partly explained by admixture patterns variation among Mexicans. Population genetic has insight into the high genetic variability of Mexicans, mainly described through HLA gene studies with anthropological and biomedical importance. A prospective, case-control study was performed. In this study, we recruited 146 SLE patients, and 234 healthy individuals were included as a control group; both groups were admixed Mexicans from Mexico City. The HLA typing methods were based on Next Generation Sequencing and Sequence-Based Typing (SBT). The data analysis was performed with population genetic programs and statistical packages. The admixture estimations based on HLA-B and -DRB1 revealed that SLE patients have a higher Southwestern European ancestry proportion (48 ± 8%) than healthy individuals (30 ± 7%). In contrast, Mexican Native American components are diminished in SLE patients (44 ± 1%) and augmented in Healthy individuals (63 ± 4%). HLA alleles and haplotypes’ frequency analysis found variants previously described in SLE patients from Mexico City. Moreover, a conserved extended haplotype that confers risk to develop SLE was found, the HLA-A∗29:02∼C∗16:01∼B∗44:03∼DRB1∗07:01∼DQB1∗02:02, pC = 0.02, OR = 1.41. Consistent with the admixture estimations, the origin of all risk alleles and haplotypes found in this study are European, while the protection alleles are Mexican Native American. The analysis of genetic distances supported that the SLE patient group is closer to the Southwestern European parental populace and farthest from Mexican Native Americans than healthy individuals. Heterogeneity of genetic admixture determines SLE susceptibility and protection in Mexicans. HLA sequencing is helpful to determine susceptibility alleles and haplotypes restricted to some populations.

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Section: Discussionmentioning

confidence: 99%