Anti-IL12A monoclonal antibody, clone NN1602-3Z48

Objective. To independently replicate the top findings from 4 published genome-wide association studies (GWAS) of susceptibility genes in Behc, et's disease (BD). Methods. We tested 14 single-nucleotide polymorphisms (SNPs) in 13 genomic loci (excluding the major histocompatibility complex [MHC], IL10, and IL23R-IL12RB2, which have already been associated with BD in Iranians) for allelic and genotypic associations with BD in 973 patients and 828 controls from Iran and performed meta-analyses of the significantly associated markers. Results. Six SNPs (in decreasing order of significance, rs7616215 located 38 kb downstream of CCR1, rs2617170 [p. Asn104Ser] in KLRC4, rs17810546 in IL12A-AS1, rs7574070 in STAT4, and rs10050860 [p. Asp575Asn] and rs13154629 in ERAP1) were nominally associated with BD in both allelic association tests (5.05 x 10(-9) <= P-allele <= 7.55 x 10(-3)) and sex-adjusted genotypic association tests (6.01 x 10(-9) <= adjusted P value <= 1.30 x 10(-2)). For all 6 SNPs tested by meta-analysis (P-meta), the association with BD was strengthened, because the direction and magnitude of association were similar across populations (e.g., for rs7574070, odds ratio [OR] for A allele 1.29 [95% confidence interval (95% CI) 1.21-1.37], P-meta = 52.34 x 10(-16); for rs7616215, OR for C allele 0.70 [95% CI 0.65-0.76], P-meta=1.54 x 10(-19); for rs17810546, OR for A allele 0.60 [95% CI 0.52-0.70], P-meta=6.34 3 10 211; for rs2617170, OR for T allele 0.76 [95% CI 0.70-0.81], P-meta=2.75 3 10 214; for rs13154629, OR for TT genotype 2.76 [95% CI 2.01-3.80], P-meta=3.57 x 10(-10)). Conclusion. This study reinforces the notion that CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 are bona fide susceptibility genes for BD, in addition to the MHC, IL10, and IL23R-IL12RB2 loci. Future genetic and functional studies are now warranted to uncover the roles of these genes in the pathogenesis of BD.

Fascioliasis is a disease caused by liver flukes. In human fascioliasis hyperendemic areas, reinfection and chronicity are the norm. Control strategies in humans require the use of egg count techniques to calculate the appropriate treatment dose for colic risk prevention. The present study investigates how fascioliasis reinfection affects liver fluke egg shedding and its relationship with the immune-regulatory response. The experimental design reproduced the usual reinfection/chronicity conditions in human fascioliasis endemic areas and included Fasciola hepatica primo-infected Wistar rats (PI) and rats reinfected at 4 weeks (R4), 8 weeks (R8), 12 weeks (R12), and negative control rats. In a longitudinal study (0-20 weeks post-infection, p.i.), serical IgG1 levels and eggs per gram of faeces (epg) were analyzed. In a cross-sectional study, the expression of the genes associated with Th1 (Ifng, Il12a, Il12b, Nos2), Th2 (Il4, Arg1), Treg (Foxp3, Il10, Tgfb, Ebi3), and Th17 (Il17) in the spleen and thymus was analyzed. In R8 and R12, transiently higher averages of epg and epg/worm in reinfected groups vs PI group were detected at least in the weeks following reinfection. The kinetics of IgG1 levels shows that reinfected groups followed a pattern similar to the one in the PI group, but transiently higher averages of IgG1 levels in reinfected groups vs the PI group were detected in the weeks following reinfection. Epg correlated with IgG1 levels and also with systemic Il10 and thymic Ifng, and Il10 expression levels. These results suggest that epg depends on the Th1 and Treg phenotype and that the determination of the fluke burden by epg is likely to be an overestimation in cases of recent reinfection in low burden situations. A strategy to facilitate the implementation of epg count techniques and the subsequent decision on the appropriate treatment dose for each patient to prevent colic risk is required.