Human immunology
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Chronic rejection predominantly manifested as bronchiolitis obliterans syndrome (BOS), still remains a major problem affecting long-term outcomes in human lung transplantation (LTx). Donor specific antibodies (DSA) and infiltration of neutrophils in the graft have been associated with the development of BOS. This study determines the role of defensins, produced by neutrophils, and its interaction with α-1-antitrypsin (AAT) towards induction of airway inflammation and fibrosis which are characteristic hallmarks of BOS. ⋯ HNPs mediated SAEC activation was completely abrogated by AAT. In conclusion, our results demonstrates that neutrophil secretory product, α-defensins, stimulate β-defensin production by SAECs causing upregulation of pro-inflammatory and pro-fibrotic signaling molecules. Hence, chronic stimulation of airway epithelial cells by defensins can lead to inflammation and fibrosis the central events in the development of BOS following LTx.
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Sepsis is associated with severe immunosuppression, evidenced by loss and dysfunction of CD3(+) lymphocytes and γδ-TCR(+) T-cells. There is limited data addressing changes in the invariant natural killer T-(iNKT) cell population with sepsis, and whether such changes correlate with clinical outcomes. Specifically, septic geriatric patients have marked mortality. How γδ-TCR(+) T-cells and iNKT-cells are altered in the settings of sepsis and advanced age, and how these changes correlate with mortality are unknown. ⋯ iNKT-cells are increased in sepsis, suggesting that they typify an evolving morbid state. This is most pronounced in geriatric non-survivors, a group demonstrating dysfunctional regulatory iNKT-cell phenotype.
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Meta Analysis
Associations between interleukin 1 polymorphisms and susceptibility to systemic lupus erythematosus: a meta-analysis.
This study determined whether interleukin 1 (IL1) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE). ⋯ This meta-analysis suggests IL1A -889 C/T polymorphism is associated with susceptibility to SLE in Europeans, and that the IL1RN*2 allele is associated with susceptibility to SLE in Europeans and Asians.
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Meta Analysis
Association between CTLA-4 polymorphisms and susceptibility to Celiac disease: a meta-analysis.
The study explored whether cytotoxic T lymphocyte antigen-4 (CTLA-4) polymorphisms confer susceptibility to Celiac disease (CD). ⋯ The CTLA-4 CT60 A/G polymorphism was associated with CD susceptibility, but no association was found between CTLA-4 +49 A/G and -318 C/T polymorphisms and CD in Europeans.
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Although short-term graft survival has been improved by recent desensitization protocols including B cell depletion therapy, little is known about risk factors of chronic antibody-mediated rejection (CAMR) in HLA-incompatible (HLA-I) renal transplantation (RTx). Twenty-six HLA-I RTx with positive donor-specific antibodies (DSA) and negative T cell cytotoxic crossmatches were compared with 88 ABO-incompatible (ABO-I) and 207 ABO-identical/compatible (ABO-Id/C) RTx. The desensitization therapy consisted of mycophenolate mofetil, rituximab and double-filtration plasmapheresis. ⋯ In addition, the remaining DRB ± DQB DSA caused CAMR in 80% of patients, while DQB DSA alone did not. The progress of subclinical CAMR within 1 year could not be circumvented by rituximab. Sustained class II (DRB ± DQB) DSA detection after RTx may pose a potential risk for developing CAMR, but negative change in class I DSA could also elicit CAMR.