Clinical Immunology Communications最新文献

The acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients and is defined by the acute onset of noncardiogenic pulmonary edema, hypoxemia, and the need for mechanical ventilation. ARDS occurs most often in the setting of pneumonia, sepsis, aspiration of gastric contents or severe trauma, and is present in ∼10% of all intensive care unit patients worldwide. Pathologic specimens from patients with ARDS most frequently reveal diffuse alveolar damage, and laboratory studies have demonstrated both alveolar epithelial and lung endothelial injury, resulting in accumulation of protein-rich inflammatory edema fluid in the alveolar space. The current therapeutic regimen is comprised of supportive measures such as lung protective ventilation, restrictive fluid management, paralyzing drugs, and prone positioning. Although vast improvements have been made in ARDS-treatment during the last five decades, mortality among patients with severe ARDS remains at an unacceptable rate of 45%.This article reviews the evolution of the currently used definition, established pathophysiological mechanism, highlights the current best clinical practice to treat ARDS, gives a brief outlook on cutting edge trends in ARDS research and closes with an expert opinion on the subject. The ongoing digital revolution will help to individualize ARDS-treatment and will therefore presumably improve survival and quality of life.

Objectives

Elderly become more susceptible to lower respiratory tract infections, resulting in antibiotic prescriptions. Immunoglobulins (Ig) play an important role in host defense and protection against infections. Therefore, we aimed to investigate whether lower Ig levels are a risk factor for antibiotic use in the general elderly population.

Methods

After exclusion of current antibiotic users, Cox proportional-hazards regression models were performed to investigate the effect of stable serum IgM, IgG and IgA levels on time to first antibiotic prescription within the Rotterdam Study. Regression models were adjusted for age, sex, body mass index, smoking status and diabetes. We introduced quadratic terms and additionally categorized Igs to explore and quantify potential non-linearity of the association. The restricted cubic splines technique was used to plot the natural log of the hazard across Ig level.

Results

In total, 8,639 participants were included (mean age 64 years, 57% female, medium follow-up 3.2 years). No significant association between IgM and time to antibiotic prescription was observed. IgG and IgA levels (in g/L) showed a U-shaped relationship with time to antibiotic prescription (linear IgG HR 0.959, 95% CI 0.930–0.989; quadratic IgG² HR 1.002, 95% CI 1.000–1.003; linear IgA HR 0.949, 95% CI 0.910–0.990; quadratic IgA² HR 1.009, 95% CI 1.004–1.013).

Conclusion

Both low and high IgG and IgA levels were associated with a higher incidence of antibiotic prescriptions in stable middle-aged and older individuals. Increased awareness for the potential increased infection risk when persons have low or high Ig levels, even within the reference ranges, is needed.

Cutaneous T-cell lymphoma (CTCL) serves as an umbrella term for numerous lymphomas that reside in or recirculate through the skin. One such systemic lymphoma is Sézary Syndrome (SS). Although SS is not as common in Skin of Color (SOC), minority patients presenting with the condition do have a different presentation than their White counterparts. In this graphical review, we provide an overview of SS immunopathogenesis and varying presentations. Additionally, a summary of current treatment options is provided, highlighting ongoing clinical trials and opportunities to include SOC patients to promote health equity. SOC patients often have poorer prognosis due to biological differences and health disparities resulting in delayed diagnosis. This exemplifies the potential advantages and promising solutions of precision medicine implementation. To this end, the impact and benefits of precision medicine are summarized.

Mycosis fungoides (MF) is the most common subtype of Cutaneous T-Cell Lymphoma (CTCL). Patients with Skin of Color (SOC) may be disproportionately impacted by MF due to delayed diagnoses, limited research, and treatment differences. In this graphical review, we provide an overview of MF immunopathogenesis and demonstrate how it manifests differently in SOC patients. We also provide our hypothesis for why the disease process can result in a myriad of clinical presentations in SOC patients. Last, we provide a summary of current treatment options, highlighting ongoing clinical trials and opportunities to include SOC patients to promote health equity.

The newly discovered SARS-CoV-2 Omicron (B.1.1.529) variant is the most antigenically unique SARS-CoV-2 variant of concern to date, which is presently prevalent across most of the world. According to a number of studies, the Omicron variant causes a restricted immune response after infection. A critical component of study is determining the efficacy of Omicron-induced immunity and if it is cross-protective against other variants.

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.