ABSTRACT
BACKGROUND: To predict primary failure of infliximab (IFX) therapy in Crohn's disease (CD) and to identify patients who maintain long-term effectiveness to IFX is currently not feasible. Some genetic variations are proposed as potential biomarkers. AIM: We assessed a set of single nucleotide polymorphisms (SNPs) in genes related to the IFX mechanism of action and the presence of HLA-DQA1 * 05 allele on the primary response and long-term durability in CD patients. METHODS: A multi-centre cross-sectional study of IFX-exposed adult patients with CD was undertaken. Treatment persistence and time to failure were co-primary endpoints. DNA from the 131 patients was genotyped. Association between SNPs and clinical variables with IFX persistence was assessed. RESULTS: Failure to IFX was documented in 65 (49.6%) out of 131 patients. IFX persistence was associated either with carrying the TT genotype in ADAM17 rs10929587 (ORa=0.2; 95%CI=0.1-0.8; p = 0.021), or the CC genotype in SLCO1C1 rs3794271 (ORa=0.2; 95%CI=0.1-0.7; p = 0.008), according to multivariate logistic regression. In contrast, previous bowel resection increased the risk of IFX failure (ORa=2.8; 95%CI=1.1-7.3; p = 0.025). Cox regression analysis confirmed these findings and also identified IL23R rs10489629-TT (HRa 0.41; 95%CI=0.22-0.75; p = 0.004) and concomitant immunosuppressants (HRa 0.46; 95%CI=0.27-0.77; p = 0.003) as protection from IFX failure. However, no association between HLA-DQA1 * 05 allele and persistence of IFX therapy was found, with similar failure rates among carriers and non-carriers (52.8% vs. 47.4%, respectively; p = 0.544). CONCLUSIONS: SNPs rs10929587-TT in ADAM17, rs10489629-TT in IL23R and rs3794271-CC in SLCO1C1, together with no previous bowel surgery and concomitant immunosuppression, were identified as protection from failure to IFX.
Subject(s)
Crohn Disease , Humans , Adult , Infliximab/therapeutic use , Crohn Disease/drug therapy , Crohn Disease/genetics , Polymorphism, Single Nucleotide/genetics , Gastrointestinal Agents/therapeutic use , Cross-Sectional Studies , Treatment Outcome , ADAM17 Protein/genetics , Receptors, Interleukin/genetics , Receptors, Interleukin/therapeutic useABSTRACT
BACKGROUND: Our objective in this study was to determine the effects of early renal transplantectomy on patients and the production of anti-human leukocyte antigen (anti-HLA) antibodies. METHODS: Between January 2003 and May 2017, we analyzed a group of patients for the presence of specific HLA class I and/or II donor-specific antibodies (DSA), their panel-reactive antibodies (PRA), and the time period in which the antibodies were still detectable after transplantectomy. RESULTS: Anti-HLA antibodies were detected in 60.8% of patients, 60.8% and 52.2% of those patients had anti-class I and anti-class II antibodies, respectively. DSA were detected in 91.7% of the anti-HLA class I patients. Class II DSA were detected all of the patients with anti-HLA class II antibodies. The average (mean ± SD) PRA levels in our patients after transplantectomy was 60 ± 34% in class I and 63 ± 36% in class II. CONCLUSION: Anti-HLA antibodies can be detected well after transplantectomy. Even if the kidney allograft had been transplanted for only a short time, when the intensity of immunosuppression was the highest, many patients developed anti-HLA antibodies. The patients who continued with immunosuppression after transplantectomy did not develop anti-HLA antibodies.
Subject(s)
Antibodies/blood , Antilymphocyte Serum/blood , Immunosuppression Therapy/adverse effects , Kidney Transplantation/adverse effects , Antibodies/immunology , Antilymphocyte Serum/immunology , Female , Graft Rejection/immunology , Graft Rejection/surgery , Histocompatibility Antigens Class I/blood , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/blood , Histocompatibility Antigens Class II/immunology , Humans , Immunosuppression Therapy/methods , Kidney Transplantation/methods , Male , Middle Aged , Reoperation/methods , Thrombosis/immunology , Thrombosis/surgery , Time FactorsABSTRACT
SETTING: In tuberculosis both host protection and most pathogenic mechanisms depend on T lymphocytes. After activation by mycobacterial antigens, T cells both secrete interleukin-2 (IL-2) and express a high affinity receptor for this molecule (IL-2R) on their own surface. A soluble fraction of IL-2 receptor (sIL-2R), released from cell membrane, is detectable in serum and its concentration is known to be elevated in tuberculosis. OBJECTIVE: To ascertain the role of sIL-2R as an indicator of clinical evolution and response to antituberculosis treatment. DESIGN: A prospective study, in which we have measured serum sIL-2R in 52 patients (42 with active and 10 with inactive pulmonary tuberculosis) and in 36 healthy controls. In 20 patients, serum sIL-2R levels were measured serially throughout the treatment. Levels of sIL-2R were correlated to clinical and radiological parameters. RESULTS: Serum sIL-2R was significantly increased in patients with tuberculosis as compared to healthy subjects. Both the radiological findings and the clinical state of patients showed a good correlation with sIL-2R. All patients with normal values of sIL-2R 6 months after starting therapy had a favourable clinical evolution. CONCLUSION: Serum sIL-2R is a useful marker of the clinical state and evolution of patients with pulmonary tuberculosis. The detection of permanently high values beyond 3-6 months of treatment suggests that additional drugs or prolonged administration would be advisable in order to ensure full recovery.
