Clinical Immunology Communications最新文献

X-linked inhibitor of apoptosis (XIAP) deficiency is a primary immunodeficiency associated with recurrent hemophagocytic lymphohistiocytosis (HLH) episodes. The clinical phenotypes of XIAP deficiency vary, ranging from splenomegaly to life-threatening inflammation. We report a case of XIAP deficiency with unusual late-onset HLH presentation likely triggered by a drug allergy. A previously healthy adolescent boy presented to the hospital with fever and rash seven days after starting antibiotics for a neck abscess. Laboratory evaluation demonstrated cytopenias, elevated liver enzymes, and increased inflammatory markers. Initially, antibiotics were discontinued due to concern for drug rash. He continued to deteriorate clinically and became hypotensive. Additional testing revealed decreased NK cell function, as well as elevated ferritin, triglycerides, and soluble IL-2 receptor. SLAM-Associated Protein (SAP) and XIAP evaluation by flow cytometry demonstrated decreased XIAP expression. Subsequently, genetic testing revealed a known pathogenic mutation in BIRC4 (c.421_422del), confirming the diagnosis of XIAP deficiency.

RNA viruses have been posited as triggers for Juvenile Dermatomyositis (JDM). The COVID-19 pandemic proved a unique opportunity to observe the effect of a novel RNA virus on JDM incidence and phenotype. We found the incidence of JDM increased from average of 6.9 cases per year from 2012 to 2019 to 9 cases per year from 2020 to 2021. We compared markers of disease activity in the patients diagnosed with JDM prior to and during the pandemic and found that patients diagnosed with JDM during the pandemic had significantly lower average NK cell counts 90.75(± 76) vs 163(±120) (P = 0.038) and NK cell percentage 3.63% (±2.3) vs. 6.6% (±4.1), (P = 0.008). Other markers of JDM did not significantly change. This study suggests that COVID-19 may be a viral trigger for JDM in selected cases and that NK cell dysregulation may be of particular interest in future research of virally triggered JDM.

Autoimmune neutropenia (AIN) of early childhood is caused by autoantibodies against antigens on the neutrophil membrane. Human leukocyte antigens (HLA) have previously been associated with AIN. This study investigated HLA-DRB1 and HLA-DQB1 alleles in 160 antibody positive patients and compared with 1000 controls. Increased risk was observed for DRB1*10, DRB1*14, DRB1*16 and DQB1*05, and lower risk for DRB1*04, DRB1*13 and DQB1*03. Haplotypes with higher risk included: DRB1*10/DQB1*05, DRB1*14/DQB1*05 and DRB1*16/DQB1*05, while DRB1*04/DQB1*03, DRB1*07/DQB1*02, and DRB1*13/DQB1*06 were associated with lower risk. Associated HLA-DRB1 and –DQB1 differed between patients positive for anti-HNA-1a-specific antibodies and patients positive for broad reactive anti-FcγRIIIb antibodies. DRB1*01, DRB1*04 and DQB1*03 was only associated for anti-HNA-1a positive, and DRB1*10 was restricted to broad reactive anti-FcγRIIIb positive. Strong association between AIN and HLA-DRB1 and -DQB1 alleles and haplotypes suggested that they play a role in susceptibility or protection. Different associations regarding FcγRIIIb antibody specificities could indicate disease heterogeneity.

Despite the great impact of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2), we still lack techniques that allow us to anticipate the natural history of the disease in order to avoid or shorten the clinical period of the disease. The values of nine cytokines were measured in COVID-19+ patients admitted to the Hospital Universitario Reina Sofía (HURS) using flow cytometry. The cytokines measured are IL-1ß, IL-6, MCP-1, IP-10, IL-10, IL-8, IL-12, IFN-γ and TNF-α. Given the absence of previous studies on cytokine values in healthy patients using the flow cytometry technique, and the low availability of resources in the first waves of COVID-19, a control group was lacking, all resources were employed for monitoring sick patients. However, this study has revealed a greater increase in two specific cytokines, which are also found to be higher than the rest in healthy patients: MCP-1 and IP-10, which are mainly responsible for cytokine storm and post-disease thrombosis.

Host-defense peptides (HDPs) such as human beta-defensin-2 (hBD-2) and cathelicidin (LL37) are essential components of innate immune response against tuberculosis (TB) infection, which could also be assessed for diagnostic potential in spectrum of TB infection. We assessed mRNA and circulating levels of HDPs in pulmonary TB (PTB) patients and their household contacts (HHCs). hBD-2 and LL37 were found to be significantly higher in both PTB and HHCs suggestive of bacterial exposure which was further corroborated by higher levels of HDPs in mantoux positive HHCs (latent TB). Higher levels of HDPs in HHCs may suggest protective host response against infection as indicated by inverse relation of LL37 with disease severity in PTB. Both peptides demonstrated high levels of sensitivity and specificity, although hBD-2 proved to be a better HDP for distinguishing LTBI from active TB at a cutoff of 3904 pg/ml. However, follow-up studies are required to validate these findings.

In the aging population, the longitudinal decrease in the secretion of steroidal and polypeptides growth hormones is directly associated with accumulation of senescent cells in tissues and organs. The cellular hypo-replicative senescence state is caused by metabolic stress and persistent DNA damage, which lead to the activation of the p16^INK4a cell-cycle inhibitor, retinoblastoma and p53 pathways. Aging increases the susceptibility to physical frailty, sarcopenia, diabetes, atherosclerosis, infectious disease and cancer in the older adults. As a consequence of immunosenescence and reduced immunoreactivity of the innate and adaptive systems, seniors have a weak response to vaccination. The high doses of vaccines have been recommended to boost growth and activation of memory T and B cells in non-responsive older individuals, but it is not sufficient for long-term protection. The treatment with recombinant human growth hormone has been shown to regenerate thymus and increase the repertoire of naive T cells CD4+ and CD8+ T cell and B cell subsets in people with age-related diseases, chronic viral infection and immunodeficiencies. This review presents an update on senescence biology and their clinical immunological manifestations in the elderly. We describe possible immune mechanisms by which personalized recombinant growth hormone therapy could act to prolong the effectiveness of the vaccines recommended to older adults.

We analyzed immune response to SARS-CoV-2 vaccination by measuring specific IgG titers and T-cell reactivity to different SARS-CoV-2 peptides in multiple sclerosis patients taking different disease-modifying treatments. Of the 88 patients included, 72 developed any kind of immune response after vaccination. Although DMTs such as fingolimod and anti-CD20+ treatments prevented patients from developing a robust humoral response to the vaccine, most of them were still able to develop a cellular response, which could be crucial for long-term immunity. It is probably advisable that all MS patients take additional/booster doses to increase their humoral and/or cellular immune response to SARS-CoV-2.

The pandemic caused by the SARS-CoV-2 coronavirus has been especially detrimental to patients with end-stage renal disease. History with other vaccines suggests that patients with renal disease may not respond adequately to the SARS-CoV-2 vaccine. The aim of this study is to evaluate the immunity to SARS-CoV-2 mRNA vaccines in renal patients. Post SARS-CoV-2 vaccination first, and after the booster dose, antibodies and cellular immunity were studied in patients on hemodialysis (N = 20), peritoneal dialysis (N = 10) and renal transplantation (N = 10). After the two doses of vaccine, there was an effective immunity in dialysis patients, with 100% seroconversion and 87% detection of cellular immunity (85% in hemodialysis and 90% in peritoneal dialysis). In contrast, in renal transplant recipients there was only 50% seroconversion and cellular immunity was detected in 30% of patients. After the booster dose, all dialysis patients achieved a cellular and antibody immunity, whereas in transplant patients, despite improvement, 20% did not produce antibodies and in 37.5% cellular immunity could not be detected. The mRNA vaccine plus booster performs excellently in dialysis patients, whereas in kidney transplant recipients, despite the booster, complete immunization is not achieved.