الفهرس 
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Abstract
Antiphospholipid syndrome (APS) represents a rare acquired hypercoagulable condition influenced by an immunological response, identified by thrombosis in the microvascular, arterial, or venous systems, as well as particular adverse consequences of pregnancy, with the presence of persistent antiphospholipid antibodies (aPLs) (Walter et al., 2021). Over the last few years, there has been a great understanding of APS management, phenotype, and pathogenesis, as well as the establishment of international transdisciplinary research collaborations all of which have contributed to better patient care and health outcomes in APS (Yang et al., 2021).
Toll-like receptors (TLRs) represent a type of pattern recognition receptor (PRR) crucial for the innate immune system (Sadik et al., 2015). Activation of TLRs triggers host signaling cascades as an anti-invasion defense mechanism and to heal injured tissues (Wang et al., 2016), producing immunological modulators and inflammatory cytokines. Conversely, intense activation of TLR impairs immunological homeostasis via continuous pro-inflammatory cytokines and chemokines generation, leading to several diseases (Wong et al., 2009).
Because of the clinical importance of predicting the development of PAPS and as the evaluation of the association between TLR4 and TLR10 polymorphisms and PAPS pathogenesis has not yet been addressed in Egyptians, this study aimed to assess the genetic relationship between TLR4 D299G and T399I variants, and TLR10 N241H and I775V variants with the possibility of PAPS development in an Egyptian PAPS sufferer.
Sixty-five adult, unrelated female patients suffering from primary APS and admitted to obstetrics, gynecology, and vascular clinics at Ain Shams University hospitals, in Cairo, Egypt, were enrolled in the current study. The control group consists of 45 healthy subjects recruited from committees and colleges in the same region and matched to the other group for gender, age, and ethnicity. The PCR-RFLP technique was used to find the targeted polymorphism in TLR4 and TLR10 genes, followed by DNA sequencing for validation of RFLP results.
Results obtained from the current study demonstrate the following:
A total of 50 out of 65 PAPS patients had single aPL positivity, ten had double aPL positivity, and 7.7% had triple positivity.
The majority of patients with PAPS had obstetric morbidity (52.3%). On the other hand, 47.7% of patients with PAPS had previously suffered thrombotic events.
Obstetric events included one or more fetal death at 10 weeks of gestation or greater in 21 cases (32.3%), three or more consecutive pregnancy losses at less than 10 weeks of gestation (18.5%), and one or more premature births occurring at less than 34 weeks due to severe preeclampsia or placental insufficiency (1.5%).
Among patients with thrombotic complications, 22 subjects had venous thrombosis while nine participants had arterial thrombosis. Of these, 21 participants had vein thrombosis (DVT) in a lower extremity (32.3%) and one participant had DVT in an upper extremity (1.5%).
The distributions of genotypes and alleles of the TLR4:
• The AA genotype of TLR4 D299G was detected in all subjects, while the AG and GG genotypes were not detected in any subject.
• The CC genotype of TLR4 T399I was detected in all subjects, while the CT and TT genotypes were not detected in any subject.
The distributions of genotypes and alleles of the TLR10:
• PAPS patients had a higher TLR10 c.2323A allele frequency than normal ones.
• No significant change was found in allele frequency or genotype distribution for TLR10 I775V.
• TLR10 N241H SNP was associated with a lower risk of PAPS in controls under the different genetic models; homozygous codominant, dominant, recessive and allelic models.
No significant relation was found between TLR4 targeted SNPs & tested TLR10 I775V SNP and PAPS risk in controls under any of the tested genetic models.