Background and Aims

At the moment, there are no predictive markers of immune adverse events (IAE), which makes timely diagnosis very difficult. In 2011 criteria for determining Autoimmune-Inflammatory syndrome induced by adjuvants (ASIA) were proposed (Y. Shoenfeld, 2011). This study aims to identify the clinical manifestations of ASIA, as well as to determine the extent to which the influence of trigger factors listed in the “ASIA Questionnaire” are significant.

Methods

We examined patients (n=50) being treated for solid tumors at St. Petersburg City Clinical Oncology Center. Among the patients, 30 took nivolumab, 15-pembrolizumab, and 5-combined immunotherapy. To assess the impact of exogenous and endogenous trigger factors, all patients were interviewed using the “ASIA” standardized questionnaire. Supported by Grant (contract № 14.W03.31.0009 13.02.2017).

Results

The signs of ASIA syndrome were found in 72 % (36/50) of patients. The most frequent clinical manifestations were arthralgia-33% (12/36) and rash - 28% (10/36). The development of thyroiditis was detected in 8% (3/36) of cases, and hepatitis in 6% (2/36). No relationship was found between the development of ASIA and the influence of trigger factors, the previous presence of ASIA symptoms, and the type of drug used.

Conclusions

Our results exceed the frequency of complications according to the literature data, which may be due to a more extensive list of analyzed criteria and subjective assessment of the patient's condition. Development of specific complications corresponds to the results of past studies. It was shown that studied ICI induce ASIA symptoms regardless previous clinical symptoms of autoimmune processes and different types of trigger affection.

Background and Aims

Sarcoidosis and tuberculosis have several similar clinical and pathogenetic characteristics, what makes some researchers consider a common pathogenesis for these diseases. HLA-genotypes are known as a genetic predisposition factor for many diseases and are studied for sarcoidosis and tuberculosis patients. However there is no comparative study of genetic predisposition for sarcoidosis or tuberculosis development.

The aim of this study was to analyze the relationship between HLA genotypes and the development of sarcoidosis and tuberculosis.

Methods

Original (n=19) and review articles (n=14) published in various online databases from 1960 to 2019 were studied. The papers were selected according to key words: sarcoidosis, tuberculosis, HLA-genotype, genetic predisposition.

Results

The study results showed opposite effects of the HLA genotypes associated with a predisposition to the development of sarcoidosis or tuberculosis. It was revealed, the genotypes predisposing to the development of sarcoidosis (HLA-DRB1*03/07/15) have protective properties against the development of tuberculosis. Moreover, genotypes causing its development (HLA-DRB1*04) have a protective effect on the development of sarcoidosis. Some of these results might be explained by the weak affinity of MHC molecules for mycobacterial antigens in patients with HLA-DRB1*04 genotype and the strong affinity of MHC proteins for bacterial antigens in individuals with HLA-DRB1*03: 01 genotype

Conclusions

The HLA system may determine the development of the immune response in contact with mycobacteria. It was shown that HLA-DRB1*04 genotype predispose to tuberculosis development, while the HLA-DRB1*03/07/15 genotypes to sarcoidosis. Determining the HLA genotypes may result in assessing a risk degree for developing tuberculosis or sarcoidosis in the foci of mycobacterial infection.

Background and Aims

Sarcoidosis is one of granulomatous diseases. Granuloma formation is a result of lymphocytes activation. In different studies the changes in B cells and T cells subsets in blood and broncho-alveolar fluid were found. Alteration of B cells and T cells subsets might be the result of T follicular helpers (Tfh) activity. Nowadays there is no data about the role of T follicular helpers in sarcoidosis.

The aim of this study was to determine the peripheral blood Tfh in patients with sarcoidosis.

Methods

In a prospective comparative study conducted in 2016-2018 we analyzed peripheral blood circulating Tfh cell subsets in 34 patients with first diagnosed sarcoidosis and 30 healthy donors using multicolor flow cytometry. The statistical comparisons of data were performed using the Mann–Whitney U test and ROC analysis with GraphPad Prism Version 6.0 (USA).

Results

According to Mann-Whitney U test in sarcoidosis patients in comparison with healthy subjects the level of Tfh1 in effector and central memory was found to be decreased and the level of Tf2, Tfh17 increased (p<0.01). According to the ROC analysis the difference significant for diagnostic purpose wasn`t found (AUC ≤0.7).

Conclusions

In sarcoidosis group were found an increase of Tfh2 and Tfh17 cells, that induce antibody secretion in B cells, and a decrease in Tfh1 cells, that regulate the apoptosis of B cells. This results might be the additional confirmation of autoimmune origin of sarcoidosis.