Etiological aspects of chronic pathology of the lymphepithelial pharyngeal ring in children at the present stage

The lymphoepithelial pharyngeal ring is located in the entrance gate and is constantly exposed to infectious agents. Currently, chronic pathology of the lymphoepithelial pharyngeal ring remains one of the most common problems in the practice of a pediatric doctor. Hypertrophy of the pharyngeal tonsil, chronic adenoiditis, which occurs in 35.3% of children under the age of 7 years, and chronic tonsillitis, which occurs in 15-63% of cases, are among the most common diseases of childhood. Taking into account the wide range of infectious microbiota that contributes to the development of chronic pathology of the lymphoepithelial pharyngeal ring, the issue of differential diagnosis of the etiology of the disease and the selection of adequate treatment regimens remains relevant. In most cases, at the present stage, the approach to the treatment of patients with chronic inflammation of the lymphoid ring of the pharynx in children is reduced to replacing the surgical method with a conservative one with the appointment of immunocorrective and immunomodulatory drugs. The lack of a positive effect of the ongoing conservative treatment, clinical and laboratory signs of persistent streptococcal infection say us about the need for surgical treatment. At the same time, a group of frequently ill children requires special attention with the development of new regimens of the immunocorrecting and immunomodulating drugs usage.

Andrographolide: A Herbal-Chemosynthetic Approach for Enhancing Immunity, Combating Viral Infections, and Its Implication on Human Health

Plants consistently synthesize and accumulate medically valuable secondary metabolites which can be isolated and clinically tested under in vitro conditions. An advancement with such important phytochemical production has been recognized and utilized as herbal drugs. Bioactive andrographolide (AGL; C20H30O5) isolated from Andrographis paniculate (AP) (Kalmegh) is a diterpenoid lactones having multifunctional medicinal properties including anti-manic, anti-inflammatory, liver, and lung protective. AGL is known for its immunostimulant activity against a variety of microbial infections thereby, regulating classical and alternative macrophage activation, Ag-specific antibody production during immune disorder therapy. In vitro studies with AGL found it to be effective against multiple tumors, neuronal disorders, diabetes, pneumonia, fibrosis, and other diverse therapeutic misadventures. Generally, virus-based diseases like ZIKA, influenza A virus subtype (H1NI), Ebola (EBOV), Dengue (DENV), and coronavirus (COVID-19) epidemics have greatly increased scientific interest and demands to develop more effective and economical immunomodulating drugs with minimal side effects. Trials and in vitro pharmacological studies with AGL and medicinally beneficial herbs might contribute to benefit the human population without using chemical-based synthetic drugs. In this review, we have discussed the possible role of AGL as a promising herbal-chemo remedy during human diseases, viral infections and as an immunity booster.

Disease activity and humoral response in patients with inflammatory rheumatic diseases after two doses of the Pfizer mRNA vaccine against SARS-CoV-2

BackgroundThe registration trials of messenger RNA (mRNA) vaccines against SARS-CoV-2 did not address patients with inflammatory rheumatic diseases (IRD).ObjectiveTo assess the humoral response after two doses of mRNA vaccine against SARS-CoV-2, in patients with IRD treated with immunomodulating drugs and the impact on IRD activity.MethodsConsecutive patients treated at the rheumatology institute, who received their first SARS-CoV-2 (Pfizer) vaccine, were recruited to the study, at their routine visit. They were reassessed 4–6 weeks after receiving the second dose of vaccine, and blood samples were obtained for serology. IRD activity assessment and the vaccine side effects were documented during both visits. IgG antibodies (Abs) against SARS-CoV-2 were detected using the SARS-CoV-2 IgG II Quant (Abbott) assay.ResultsTwo hundred and sixty-four patients with stable disease, (mean(SD) age 57.6 (13.18) years, disease duration 11.06 (7.42) years), were recruited. The immunomodulatory therapy was not modified before or after the vaccination. After the second vaccination, 227 patients (86%) mounted IgG Ab against SARS-CoV-2 (mean (SD) 5830.8 (8937) AU/mL) and 37 patients (14%) did not, 22/37 were treated with B cell-depleting agents. The reported side effects of the vaccine were minor. The rheumatic disease remained stable in all patients.ConclusionsThe vast majority of patients with IRD developed a significant humoral response following the administration of the second dose of the Pfizer mRNA vaccine against SARS-CoV-2 virus. Only minor side effects were reported and no apparent impact on IRD activity was noted.

Vaccines in Children with Inflammatory Bowel Disease: Brief Review

Incidence of inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing worldwide. Children with IBDs have a dysfunctional immune system and they are frequently treated with immunomodulating drugs and biological therapy, which significantly impair immune system functions and lead to an increased risk of infections. Vaccines are essential to prevent at least part of these infections and this explains why strict compliance to the immunization guidelines specifically prepared for IBD patients is strongly recommended. However, several factors might lead to insufficient immunization. In this paper, present knowledge on the use of vaccines in children with IBDs is discussed. Literature review showed that despite a lack of detailed quantification of the risk of infections in children with IBDs, these children might have infections more frequently than age-matched healthy subjects, and at least in some cases, these infections might be even more severe. Fortunately, most of these infections could be prevented when recommended schedules of immunization are carefully followed. Vaccines given to children with IBDs generally have adequate immunogenicity and safety. Attention must be paid to live attenuated vaccines that can be administered only to children without or with mild immune system function impairment. Vaccination of their caregivers is also recommended. Unfortunately, compliance to these recommendations is generally low and multidisciplinary educational programs to improve vaccination coverage must be planned, in order to protect children with IBD from vaccine-preventable diseases.

Bystander Memory T Cells and IMiD/Checkpoint Therapy in Multiple Myeloma: A Dangerous Tango?

In this review article we discuss the role of the memory T cells in multiple myeloma (MM) and how they may influence immune responses in patients that received immunomodulating drugs and check point therapy.

Daratumumab in combination with proteasome inhibitors, rapidly decreases polyclonal immunoglobulins and increases infection risk among relapsed multiple myeloma patients: a single center retrospective study

Background: Daratumumab (Dara) is generally well tolerated, but is associated with increased risk of infection. Methods: We investigated hypogammaglobinemia occurrence in different Dara-based regimens. Multiple myeloma (MM) patients were treated with ⩾2 cycles of Dara-based therapy during 2016–2020, mainly for relapsed/refractory disease. Data on patient characteristics, treatment regimens, polyclonal IgG (poly-IgG) and uninvolved free light chain (Un-FLC) levels during treatment, as well as predictors for hypogammaglobinemia and predictors for infections, were evaluated retrospectively. Results: A total of 84 patients, median age 67.2 years, were included. Dara, mainly as ⩾2 line therapy (88.1%, n = 74), was combined with immunomodulating drugs (IMiDs) (53%), proteasome inhibitors (PIs) (15%), IMiDs-PIs (11%), or dexamethasone only (21%). Median treatment duration was 13 months. Median Poly-IgG levels at 0, 2, and 4 months were 7.1 g/l, 4.5 g/l, and 4 g/l, respectively, and remained low throughout treatment. Lower poly-IgG pre-Dara ( p = 0.001) and Dara-PIs (±IMiDs) regimen were associated with lower poly-IgG levels at 4 months ( p = 0.03). Only patients treated with Dara monotherapy had partial immune reconstitution, reflected by resumption of IgM levels. Most (85%) patients developed ⩾1 infections, mostly grade 1–2 respiratory (76%). A lower poly-IgG level post Dara (RR = 1.137 p = 0.026) predicted increased risk of any infection. Intravenous immunoglobulin (IVIG) was associated with a significant decrease in all infections. Conclusion: Relapsed MM patients treated with Dara, often experience persistent hypogammaglobinemia, irrespective of responsiveness to treatment. Infections, especially respiratory, are frequent and apparently related to low Poly-IgG levels. IVIG should be considered for reducing infections in these patients.

Neurosarcoidosis - an ever-present clinical challenge

Sarcoidosis afflicts the central nervous system more frequently than previously believed. Neurological symptoms are present in roughly a half of patients, and depend of the location in central nervous system. The probability of spontaneous regression is significantly less when compared to other forms of sarcoidosis, which means that the proper diagnosis and treatment is paramount. Even when properly treated, functional defects are not uncommon. Majority of these patients require immunomodulating drugs and continuous follow-up. New immunomodulating drugs, especially biological agents, have shown to be significantly more effective, with fewer side effects, and are important when corticosteroids could not be applied. Less invasive methods, such as cerebrospinal analysis, help greatly in the diagnostics procedure, and require further research and improvement