Anti-FASLG monoclonal antibody, clone 14C2

Autoimmune diseases like celiac disease (CeD) and ulcerative colitis (UC) show a common genetic background defined by the existence of shared susceptibility loci. We aimed to go deeper into this common genetic background through performing a cross-disease study based on gene expression. We measured the expression of 21 genes located in 13 CeD-UC susceptibility regions, and 10 genes in five CeD risk regions. Determinations were carried out in colon/rectum samples from 13 UC patients (inflamed and uninflamed tissue) and four colon samples from controls. Duodenal samples from 19 CeD patients and 12 controls were used for comparisons. Differences were analyzed using the Bayesian method. The shared chromosomal regions containing TNFAIP3, PTPN2, ICOSLG, C1orf106, and IL21 showed similar results in both diseases. FASLG, PLEK, CCR4, and TAGAP, all located in CeD risk loci, were up-regulated in both CeD and UC patients. Finally, ZFP36L1, ZMIZ1, PUS10, UBE2L3, and BACH2 showed opposite results in CeD and UC. A high complexity underlies autoimmune common susceptibility loci, as the expression pattern of the studied genes does not always correlate with the one expected attending to the apparent genetic background. Differentially expressed genes such as ZFP36L1, ZMIZ1, PUS10, and BACH2 deserve further research in autoimmune diseases.

FAS, together with FASLG, triggers germ cell apoptosis, which occurs in various stages of mammalian testicular development. Single nucleotide polymorphisms (SNP) in the promoter regions of these two genes can influence their transcriptional activities and result in abnormal cell apoptosis, thus leading to spermatogenesis impairment. Therefore, it is reasonable to postulate that FAS and FASLG SNP may be associated with idiopathic azoospermia or severe oligozoospermia. To test this hypothesis, the distributions of FAS -1377G/A and -670A/G SNP and FASLG -844C/T SNP were studied in Hart Chinese men. These SNP were genotyped by polymerase chain react ion-restrict ion fragment length polymorphism (PCR-RFLP) in 203 infertile men with idiopathic azoospermia or severe oligozoospermia and in 246 proven fertile controls. Frequencies of FASLG -844CC, CT and TT genotypes among infertile men were significantly different from those among controls (P = 0.024). Men with FASLG -844TT genotype had an increased risk of idiopathic azoospermia or severe oligozoospermia compared with those with CC and CT genotype (odds ratio 2.72, 95% confidence interval 1.25-5.93). The results suggest that FASLG -844C/T SNP may be a genetic predisposing factor of idiopathic azoospermia or severe oligozoospermia among Han Chinese men.