The Clinical and Immunological Activity Depending on the Presence of Interferon γ in Primary Sjögren’s Syndrome—A Pilot Study

The upregulation of IFN pathways and their stimulated genes is associated with primary Sjögren’s syndrome (pSS). The recent studies also indicate the involvement of interferon γ (IFNγ) in the pathogenesis of pSS. The study aimed to assess the clinical and immunological activity depending on the concentration of IFNγ in the peripheral blood in pSS patients. Methods: The study group consisted of patients over 18 years of age with a confirmed diagnosis of pSS. Based on the collected data, disease activity was assessed using the EULAR Sjögren’s syndrome disease activity index (ESSDAI) and the EULAR Sjögren’s syndrome patient reported index (ESSPRI). Results: Among 40 pSS patients, 33 (82%) showed increased levels of IFNγ. The group with positive IFNγ was younger (43 years) than the group with negative IFNγ (57 years) (p < 0.05). In the positive IFNγ group, the time to diagnosis was shorter (p < 0.05). There was a difference in ESSDAI among patients with and without IFNγ (p < 0.05). There were no differences between the groups in ESSPRI and the presence of cryoglobulins, specific anti-SSA, and anti-SSB antibodies and in C3 and C4 hypocomplementemia. RF occurred in both groups with a similar frequency (p = 0.6), but in patients with IFNγ presence, significantly higher RF titers were observed (34.9 vs. 10.5; p < 0.05). Conclusion: In the group of patients with positive IFNγ, the mean value of RF and ESSDAI was higher. This group was also younger than patients with pSS without IFNγ.

ONTOGENETIC FORMS OF RHEUMATOID ARTHRITIS AND BEHAVIORAL TYPE A

Дебют болезни и поведенческий тип А (ПТА) являются важными характеристиками, определяющими клинические проявления хронических заболеваний. Цель работы - изучение распространенности и роли ПТА у больных ревматоидным артритом (РА) с дебютом заболевания в различные периоды онтогенеза. Обследованы 82 пациента, которые были разделены на группы в зависимости от возраста дебюта РА: в 1-ю вошли пациенты с дебютом РА в репродуктивном возрасте (18-44 года); во 2-ю - с дебютом РА в среднем возрасте (45-59 лет); в 3-ю - с дебютом РА в пожилом возрасте (60-74 года); в 4-ю - с дебютом РА в старческом возрасте (75 лет и старше). Диагностику ПТА проводили с помощью специального опросника. Группа с дебютом в репродуктивном периоде имела наибольшее число больных родственников 1-йи 2-й линии родства c РА, а также наиболее высокую частоту случаев ПТА, которая была ассоциирована с большей выраженностью таких личностных качеств, как амбициозность и враждебность. Данная группа имела наибольшее число анкилозов, а также наибольшую частоту системных поражений. 2-я группа продемонстрировала классические ревматоидные закономерности. 3-я группа с дебютом в пожилом возрасте имела наиболее благоприятную клиническую картину, в том числе наименьшую иммунную активность по уровню ЦИК, ассоциированную с наименьшей выраженностью суставного синдрома, с наименьшим числом эрозий и частотой системных проявлений. 4-я группа с дебютом в старческом возрасте продемонстрировала наиболее высокую воспалительную активность и специфическую иммунную активность по уровню ревматоидного фактора и ЦИК, а также наибольшую клиническую выраженность суставного синдрома. Таким образом, онтогенетический дебют РА определяет его клинико-лабораторные особенности, ассоциирован с наличием и характеристиками ПТА. Disease onset and type A behavioral pattern (TABP) are important characteristics of the clinical manifestations of chronic diseases. The aim of this work is to study the prevalence and role of TABP in patients with rheumatoid arthritis (RA) with the onset of the disease at different periods of ontogenesis. 82 patients were examined, which were divided into groups depending on the age of RA onset. The first group included patients with RA onset at reproductive age (from 18 to 44 years). The second group included patients with the onset of RA in the middle age (from 45 to 59 years). The third group consisted of patients with the onset of RA in old age (from 60 to 74 years). The fourth group consisted of patients with the onset of RA in old age (75 years and older). Diagnosis of TABP was carried out using a special questionnaire. The group with a debut in the reproductive period had the largest number of patients with RA of the 1st and 2nd line of relationship, as well as the highest incidence of TABP, which was associated with a greater expression of such personal qualities as ambition and hostility. This group had the highest number of ankylosis, as well as the highest frequency of systemic lesions. The second group demonstrated classic rheumatoid patterns. The third group with debut in old age had the most favorable clinical picture, incl. the lowest immunological activity in terms of the circulating immune complexes (CICs) level, associated with the lowest severity of articular syndrome, with the lowest number of erosions and the frequency of systemic manifestations. The fourth group with a debut in old age demonstrated the highest inflammatory activity and specific immunological activity in terms of rheumatoid factor and CICs levels, as well as the highest clinical severity of the articular syndrome. Thus, the ontogenetic debut of RA determines its clinical and laboratory features and is associated with the presence and characteristics of TABP.

Clinical Validation of an Immune Quiescence Gene Expression Signature in Kidney Transplantation

Background: Despite advances in immune suppression, kidney allograft rejection and other injuries remain a significant clinical concern, particularly with regards to long-term allograft survival. Evaluation of immune activity can provide information about rejection status and help guide interventions to extend allograft life. Here we describe the validation of a blood gene expression classifier developed to differentiate immune quiescence from both T cell mediated rejection (TCMR) and antibody-mediated rejection (ABMR). Methods: A five-gene classifier (DCAF12, MARCH8, FLT3, IL1R2, and PDCD1) was developed on 56 peripheral blood samples and validated on two sample sets independent of the training cohort. The primary validation set comprised 98 quiescence samples and 18 rejection samples: 7 TCMR, 10 ABMR, and 1 mixed rejection. The second validation set included 8 quiescence and 11 rejections: 7 TCMR, 2 ABMR, and 2 mixed. AlloSure donor derived cell-free DNA was also evaluated. Results: AlloMap Kidney classifier scores in the primary validation set differed significantly between quiescence (median 9.49, IQR 7.68-11.53) and rejection (median 13.09, IQR 11.25-15.28), p < 0.001. In the second validation set, the cohorts were statistically different (p = 0.028) and the medians were similar to the primary validation set. The AUC for discriminating rejection from quiescence was 0.786 for the primary validation and 0.800 for the second validation. AlloMap Kidney results were not significantly correlated with AlloSure, although both were elevated in rejection. The ability to discriminate rejection from quiescence was improved when AlloSure and AlloMap Kidney were used together (AUC 0.894). Conclusion: Validation of AlloMap Kidney demonstrated the ability to differentiate between rejection and immune quiescence using a range of scores. The diagnostic performance suggests that assessment of the mechanisms of immunological activity is complementary to allograft injury information derived from AlloSure dd-cfDNA. Together, these biomarkers offer a more comprehensive assessment of allograft health and immune quiescence.

Extraction, Characterization and Immunological Activity of Polysaccharides from Cynomorium songaricum Rupr.

Cynomorium songaricum Rupr. (CSP) have been used widely in TCM for many years, polysaccharides from CSP are main active component. In our previous research, we found that CSP play a role of immunomodulatory activity in vitro, but its mechanisms and in vivo immunomodulatory activity hadn’t been explored. In present study, we firstly extracted CSP and identified two new fractions CSP-a, CSP-b. To assess the immunomodulatory activity of CSP in vivo, cyclophosphamide (CTX)-induced immunosuppressed mice models were generated and then treated with CSP. The results demonstrated that CSP could improve thymus and spleen indices, phagocytic and clearance index, serum hemolysin, inflammatory cytokines productions in serum. To explore the mechanisms of CSP, CSP-a, CSP-b, RAW264.7 macrophages were used to evaluate the immunomodulatory activity in vitro, the results demonstrated that CSP, CSP-a, CSP-b can induce macrophage proliferation, enhance the phagocytic activity and increase cytokines expression. CSP, CSP-a, CSP-b possessed the immunomodulatory activity by inducing the phosphorylation of MAPKs. This study suggested that CSP may be useful for lessening chemotherapy-induced immunosuppression and proposed the basis for the clinical application of CSP.

ВЛИЯНИЕ ВОЗРАСТА ПЕРВОГО ОТЕЛА КОРОВ ГОЛШТИНСКОЙ ПОРОДЫ НА УРОВЕНЬ ПРОДУКТИВНОСТИ И ФАКТОРЫ ЕСТЕСТВЕННОЙ РЕЗИСТЕНТНОТИ

Исследования проведены в Московском регионе на 2 группах первотелок голштинской породы. В I группу вошли животные, срок отела которых составил 26 мес, во II — первотелки, отел которых прошел в возрасте 31 мес. Изучены показатели молочной продуктивности, воспроизводительные качества и иммунологическая активность клеток крови животных в период лактации. В результате проведенных исследований установлено некоторое превосходство по удою у первотелок с более ранним периодом отела (на 333 кг) и снижение сервис-периода на 41,2 дня. У животных более позднего срока отела на фоне достаточно устойчивого показателя корреляции сегментоядерные нейтрофилы/лимфоциты установлено снижение стабильности работы иммунной системы, что выразилось в увеличении значимых корреляций (до 6) между клеточными факторами иммунитета по сравнению с животными более раннего срока отела, у которых таких корреляций было лишь 4. Усиление корреляции IgG/IgМ до -0,388 (Р≤0,05) свидетельствует о напряженности работы иммунной системы в период лактации у первотелок с более поздним сроком отела. Установлены значимые отрицательные корреляции сегментоядерные нейтрофилы /эозинофилы (r=-0,447 и r=-0,487 (Р≤0,05) соответственно по группам, что может быть связано с усилением фагоцитирующей функции организма животных. Полученные данные могут быть полезны при оценке состояния здоровья коров голштинской породы и оптимизации сроков их первого осеменения. INFLUENCE OF THE AGE OF THE FIRST CALVING OF HOLSTEIN COWS ON THE LEVEL OF PRODUCTIVITY AND FACTORS OF NATURAL RESISTANCE The study was conducted in the Moscow region on 2 groups of Holstein cows. The first group included animals whose calving period was 26 months, and the second group included first-calves, whose calving occurred at the age of 31 months. The indicators of milk productivity and reproductive qualities of animals were studied. Immunological activity of animal blood cells during lactation. As a result of the conducted studies, some superiority in milk yield was established in cows with an earlier calving period (by 333 kg) and a reduction in the period from calving to insemination by 41.2 days. In cows of the later calving period, against the background of a fairly stable index of segmented neutrophils/lymphocytes, a decrease in the stability of the immune system was found, which was expressed in an increase in the number of reliable correlations (up to 6) between cellular immunity factors compared to animals of the earlier calving period, in which there were only 4 such correlations. An increase in the IgG/IdM correlation to (r=-0.388) (P < 0.05) indicates an increase in the intensity of the work of the immune system during lactation in animals with a later calving period. Significant negative correlations of segmental neutrophils /eosinophils were found in the groups (r=-0.447 and r=-0.487 (P < 0.05), respectively), which may be associated with an increase in the phagocytic function of the animal body. The data obtained can be useful in assessing the health status of Holstein cows and optimizing the timing of the first insemination of animals.

AB0309 SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Background:Vaccination of patients with autoimmune diseases with pneumococcal vaccines is necessary to prevent severe respiratory infections in this group of patients. The main issue of immunization of patients with systemic lupus erythematosus (SLE) remains the issue of safety.Objectives:The aim of the study was to study the safety of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with SLE.Methods:The study included 73 patients with a reliable diagnosis of SLE, of which women - 64, men - 9, aged 19 - 68 years. 69 patients received glucocorticoids (GC) 5-30 mg/day, 55- hydroxychloroquine (GCH), 37-cytostatics (CS), 27 – biologics (14 – rituximab (RTM), 11 – belimumab (BLM), 2-BLM and RTM). 1 dose (0.5 ml) of PPV23 was administered subcutaneously. 60 patients were examined within 1 year, 13 - within 2-3 months.Results:Vaccination tolerance was assessed in 73 patients: in 33 (45.2%) - vaccine reactions were absent, in 36 (49.3%) - local reactions of mild and moderate severity were noted (pain, swelling, skin hyperemia at the injection site of the vaccine), lasting from 2 to 7 days, in 1 (1.4%) - general weakness within 1 month, in 2 (2.7%) - mild diarrhea within 1 day. Vaccinal reactions were typical and completely reversible, did not require additional appointments. One patient (1.4%) developed a hyperergic reaction of the Artyus phenomenon type, which was arrested within 7 days by the use of antihistamines and topical GCs. None of the 60 patients, whose follow-up period was 1 year, had no exacerbations of the disease directly related to vaccination (i.e., in the next 2-3 months). Vaccination was carried out both at a low degree of activity (n = 33 (55%)) and remission (n = 6 (10%)), and at an average (n = 12 (20%)) and high (n = 9 (15%))) the degree of SLE activity. The dynamics of the SLE activity index SLEDAI-2k (Me) during the year was as follows: initially - 4 (2; 6), after 2-3 months - 2 (2; 4), after 12 months - 2 (2; 4). During the year, 7 out of 60 patients had a moderate exacerbation of the disease, which was not related to the vaccination in terms of timing: after 3.5-5 months (3), 12 months (4). An exacerbation occurred in 4 - with a decrease in the HA dose, in 1 - after psychological stress, in 1 - against the background of persistently high immunological activity and insufficient therapy, in 1 - without an increase in immunological activity. In 4 out of 7, exacerbation was manifested by skin rashes and articular syndrome, in 1 - by the development of panniculitis, in 2 - by leukopenia. All these symptoms were noted earlier in the period of exacerbation. In all, the exacerbation was quickly stopped by a moderate increase in the HA dose. In 60 patients, the dynamics of immunological markers of SLE was analyzed during the year after vaccination. There was no evidence of a significant increase in the immunological activity of SLE after vaccination with PPV-23. After vaccination, no new autoimmune phenomena have been identified. In the first 3 months. after vaccination, in isolated cases, there was a transient increase / decrease in SLE markers (a-DNA, ANF, C3, C4) with a subsequent return to the initial values, without symptoms of exacerbation of the disease.Conclusion:1. During the year of observation, no exacerbations were observed that were reliably associated with vaccination. 2. Vaccination with PPV-23 is safe for SLE patients during periods of low and moderate activity. If necessary, vaccination is possible at high activity without the development of adverse events. 3. The multidirectional dynamics of the main markers of SLE observed during the year reflects the instability of immunological parameters characteristic of SLE.Disclosure of Interests:None declared

Advantages of osteoarthritis combined treatment with symptomatic slow-acting drugs

The effectiveness of combined drugs, consisting of chondroitin and glucosamine (GA) in the treatment of osteoarthritis (OA) is discussed. Due to their high safety and pleiotropic effects, these drugs can be used in patients with OA (primarily with metabolic and inflammatory phenotypes) and comorbid diseases. The effect of oral chondroitin and GA on the intestinal microbiota is described: regulation of the composition, metabolic and immunological activity of intestinal microbiota. The relationship between the regular administration of chondroitin and GA and decrease in overall mortality and mortality from cardiovascular diseases, as well as the decrease of malignancy development risk is marked.