Our data show that the posttransplant presence of persisting or de novo HLA antibodies, especially if C1q binding, is associated with graft loss, even if the antibodies are not specific for mismatched donor HLA.

Genetic susceptibility to tuberculosis includes several unknown yet different loci each contributing to a small extent. Intronic polymorphisms within the interferon-g (IFN-g) gene IFNG Tþ874A and IFNG Gþ2109A correlate with the IFN-g production in vitro, and the frequency of potential high IFN-g producers was previously reported by others to be lower in patients than in controls from Sicily. The aim of this study was to determine whether there is an association between polymorphisms in the IFN-g gene and predisposition to tuberculosis. We analysed two IFNG SNPs (Tþ874A and Gþ2109A) in patients (n ¼ 253) hospitalized in Rijeka (Croatia) and controls (n ¼ 519) from the same area. Onefifth of the controls were healthy contacts of the diseased, and the rest were blood donors. IFNG alleles, their predicted haplotypes or genotypes were not associated with disease susceptibility. Thus, we could not reproduce results from Sicilian case-control study. However, T/Tþ874 (possible high IFN-g producer) and þ874A/A (putative low producer) genotypes were associated with microscopically positive-negative forms of disease. Haplotypes (Tþ874A and Gþ2109A) based on a prediction by software PHASE and subsequent genotype analysis corroborated these findings. Patients had significantly higher frequency of genotypes without T at þ874 (AA/AA; AA/AG and AG/AG) in microscopyor bacterial culture-positive groups compared with their negative counterparts. These data suggest an association with disease severity rather than susceptibility to tuberculosis in Croatian Caucasian population.

Proinflammatory conditions leading to activation of macrophages via interferonc bear an important role in host defence against intracellular bacteria such as Mycobacterium tuberculosis (Mt). Interleukin-17 plays a similar role, as it appears to be also an activator of macrophages. Recently, the TLR-10 was identified as an anti-inflammatory factor that exerts its action via association with the TLR-2 chain at the cell surface of macrophages, the latter being an Mt-binding protein.We have previously found that gene polymorphisms that either inactivate the TLR2 gene product or have a dominant-negative role are associated with tuberculosis (TB) in Croatian population. We have now extended our survey and found that single nucleotide polymorphism (SNP) in TLR10 (rs11096957) is associated with risk for TB. Homozygotes carrying the A allele are associated with predisposition to disease as analysed by the dominant model of inheritance. In contrast, SNPs in the proinflammatory IL17A and IL17F genes (rs2275913 and rs763780, respectively), found previously to correlate with the disease occurrence in Chinese population, were not significantly associated with tuberculosis in the Croatian population.

We analysed frequencies of two single-nucleotide polymorphisms (SNP) in the interferon-g (IFN-g) receptor-1 (IFNGR1) gene promoter (G-611A, T-56C) in tuberculosis patients (n ¼ 244) and compared them with controls (n ¼ 521). These frequencies were not significantly different, whether analysed independently or as haplotypes. Because these SNP affect transcription, the results suggest that the expression of the IFNGR1 gene does not confer susceptibility to disease in patients from Croatia. Further analysis revealed a significant association between the protective (CA) n polymorphism (22 repeats, 192 FA 1 ), located in the fifth intron of the IFNGR1 gene (þ16682), and GT promoter haplotype (À611; À56) that showed the strongest expression capacity. In addition to this cis relationship, the (CA) 22 allele was correlated in trans with an IFN-g SNP (IFNG G þ 2109A), which might affect the transcription of the IFNG gene. These results suggest that a particular combination of IFNG and IFNGR1 SNP might offer a better protection against tuberculosis in this population.

Primary osteoarthritis (OA) is the most common type of a joint disease. It has a polygenic risk inheritance pattern and affects older people. The etiology of this disease is not fully understood. The aim of this study was to investigate the associations between polymorphisms in pro-inflammatory interleukin-17 (IL17A and IL17F) and anti-inflammatory Toll-like Receptor 10 (TLR10) genes with the risk for development of advanced stage hip and knee primary OA in the Croatian population. A total of 500 OA patients and 597 controls were genotyped for IL17A SNP (rs2275913), IL17F SNPs (rs763780 and rs1889570), and TLR10 (rs11096957) genes. The allelic and genotypic frequencies of IL17F SNP (rs763780) showed statistically significant differences in comparisons of controls with hip-but not knee-OA patients. The major allele (T) of rs763780 was associated with the lower risk for developing hip OA (p = 7.9 × 10 , OR = 0.45, 95%CI = 0.27-0.74), whereas the minor allele (C) was associated with susceptibility to hip OA (p = 7.9 × 10 , OR = 2.24, 95%CI = 1.35-3.72). The genotype T/T was associated with the protection to hip OA (p = 3.9 × 10 , OR = 0.41, 95%CI = 0.24-0.70), and, lastly, the genotype T/C was associated with the higher risk to acquiring hip OA (p = 2.6 × 10 , OR = 2.50, 95%CI = 1.47-4.25). TLR10 SNP rs11096957 was found significantly associated with predisposition to hip OA (p = 0.04, OR = 1.41, 95%CI = 1.02-1.94) but not knee OA. Our findings suggest that hip OA in Croatian population might have a different genetic risk regarding the IL17 and TLR10 gene locus than knee OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1684-1693, 2018.