Profiling Response to Tumor Necrosis Factor Inhibitor Treatment in Axial Spondyloarthritis.

OBJECTIVE: Lack of response to tumor necrosis factor inhibitor (TNFi) agents is not uncommon, encountered during the treatment of axial spondyloarthritis (SpA) patients, and it can be classified as primary lack of response (PLR) or secondary lack of response (SLR). The primary aim of this study was to evaluate factors associated with TNFi failure types and their characteristics in axial SpA. METHODS: Adult axial SpA patients who were TNFi naive at the time of baseline evaluation and started receiving their first biologics for active axial disease were identified. Based on the clinical response to the first TNFi, patients were then stratified into 3 groups: PLR, SLR, and responders. Clinical, demographic, and laboratory data were collected and analyzed. RESULTS: There was a total of 249 axial SpA patients in the study (70.7% male, mean ± SD age 37.3 ± 12.4 years), which included PLR (n = 62), SLR (n = 93), and responders (n = 94). PLR patients tended to be older, with a lower HLA-B27 rate, a higher percentage of nonresponder axial SpA patients, and a higher baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score compared to SLR patients or responders. In multiple regression analysis, increasing age, negative HLA-B27, higher baseline BASDAI, and treatment with the soluble TNF receptor protein were the independent predictors of PLR. CONCLUSION: PLR accounted for nearly 40% of the TNFi failures in axial SpA patients. Older age, negative HLA-B27, higher baseline disease activity, and treatment with soluble TNF receptors were the independent predictors of the primary nonresponse to TNFi.

Identification of single nucleotide polymorphism markers associated with resistance to bruchids (Callosobruchus spp.) in wild mungbean (Vigna radiata var. sublobata) and cultivated V. radiata through genotyping by sequencing and quantitative trait locus analysis.

BACKGROUND: Bruchid beetles are an important storage pest of grain legumes. Callosobruchus sp. infect mungbean (Vigna radiata) at low levels in the field, multiply during grain storage and can destroy seed stocks in a few months. Resistance against bruchid beetles has been found in wild mungbean V. radiata var. sublobata TC1966 and in cultivated mungbean line V2802. RESULTS: Bruchid resistance data were obtained from recombinant inbred line populations TC1966 (V. radiata var. sublobata) × NM92 (F12) and V2802 (V. radiata) × NM94 (F7). More than 6,000 single nucleotide polymorphic markers were generated through genotyping by sequencing (GBS) for each of these populations and were used to map bruchid resistance genes. One highly significant quantitative trait locus (QTL) associated with bruchid resistance was mapped to chromosome 5 on genetic maps of both populations, suggesting that TC1966 and V2802 contain the same resistance locus. Co-segregation of all markers associated with resistance indicated the presence of only one major resistance QTL on chromosome 5, while QTL analysis based on physical map positions of the markers suggested the presence of multiple QTLs on different chromosomes. The diagnostic capacity of the identified molecular markers located in the QTL to correctly predict resistance was up to 100 %. CONCLUSIONS: Molecular markers tightly linked to bruchid resistance loci of two different mungbean resistance sources were developed and validated. These markers are highly useful for developing resistant lines.