Clinical Immunology Communications最新文献

Aim

To review the available evidence on the efficacy and safety profiles of four Interleukin-23 inhibitors in patients with Psoriatic Arthritis.

Methods

Several databases were searched till July 2022. A total of 11 RCTs with at least one treatment arm were included. All articles were in English. The primary outcomes were ACR20, HAQ-DI, PASI90, and TEAEs experienced by the patients.

Results

Compared to other groups, Guselkumab had the strongest association with ACR20 response (RR: 2.14; 95% CI: 1.84-2.49, p < 0.00001), while a mean change in HAQ-DI (MD: -0.24; 95% CI: -0.41- -0.13, p = 0.0001) and PASI90 (RR: 9.81; 95% CI: 3.18-30.22; p <0.01) were most strongly associated with Ustekinumab. TEAEs were significantly present in the Guselkumab group (RR: 1.26; 95% CI: 1.00 - 1.59; p = 0.05).

Conclusion

Although our analysis suggests that IL-23 inhibitors are efficacious at treating psoriatic arthritis, further studies are required for long-term outcomes.

The immunomodulating chemotherapeutic drugs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) have the ablity to pass the placenta during pregnancy and might affect the development of the immune system of exposed infants. In particular rituximab causes a transient and almost complete depletion of CD20 expressing B cells and can remain detectable in the infant several months after birth.

In this case series we report on the clinical and immunological outcomes of 3 infants exposed to R-CHOP during pregnancy because of maternal B-cell lymphoma and review other cases that have been published. We show that R-CHOP in pregnancy has a profound effect on the immune system in the first year of life, including B-cell lymphopenia, hypogammaglobinemia, neutropenia and decreased response to immunization. Immune monitoring of exposed infants is warranted.

Breast cancer has a heavy toll on the world's health, both in terms of morbidity and death. For women aged 35 to 54, it is the primary cause of mortality. In addition, over the preceding 2 decades, the mortality rate has not decreased noticeably. Early diagnosis and detection are still essential for enhancing patient outcomes despite substantial advancements in treatment. Also, possible to use monoclonal antibodies, but they come with a host of drawbacks, including unspecified binding, toxicity, expense, and debated clinical efficacy. Aptamers, which are small nucleic acid molecules that can bind to specific target molecules with high specificity, have instead emerged as potential theranostic treatments for breast cancer. Both for diagnosis and treatment, aptamers can be made to precisely target breast cancer cells or molecules linked to tumor progression. High binding affinity and specificity, low immunogenicity, and ease of modification are just a few of the characteristics that set aptamers apart from other delivery systems and make them desirable options for the delivery of drugs, imaging agents, or both, to breast cancer cells. In this study, we provide a comprehensive overview of the aptamer-based theranostic strategies for treating breast cancer, including aptamer selection, modifications, and imaging and drug delivery applications.

We also discussed the SELEX method for picking aptamers and why they are good breast cancer treatments. The toxicity and weak immunogenicity of some antigens do not affect aptamer selection, unlike antibodies. Compared to antibodies, they are more selective and have higher affinities. Therefore, in the future, these therapies may be used as both main therapies and adjuvants to traditional anti-HER2 therapies. We also discussed the difficulties and potential futures of theranostic approaches based on aptamers for treating breast cancer.

Juvenile dermatomyositis (JDM) is a rare autoimmune disease characterized by chronic inflammation of the skin and muscle vasculature. Loss of nailfold capillary end row loops (ERL) is associated with disease activity. We now present the first report of serious gastrointestinal (GI) events in two JDM patients, both preceded by a precipitous drop in their ERL, which contributes to the consideration of JDM as a member of the vasculitis group of myopathies. These cases demonstrate that the sudden and significant loss of ERL density appears to be a novel and reliable indicator of severe systemic microangiopathy, including gastrointestinal vasculopathy, in selected children with JDM.

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.