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The study aimed to determine the presence of a relationship between prenatal exposure to potential risk factors and the development of necrotizing enterocolitis (NEC) in premature infants. Materials and Methods: The clinical data of 99 mother-newborn couples diagnosed with Bell’s stage IIA NEC and a comparable comparison group were studied. The clinical characteristics of the main group with NEC were compared with the control group using the Student’s t-test. To assess the severity of the impact of potential risk factors, the Cochran - Mantel - Hensel method was used with the construction of a logistic regression model. Results. A statistically significant relationship was established between ampicillin prescribed to pregnant women and the occurrence of NEC in newborns. The adjusted odds ratio (OR) of prenatal ampicillin exposure was significantly greater for infants with NEC (OR 2.3, 95% CI 1.1, 4.8, P = 0.003) than for infants in the comparison group. Potential influencing factors (arterial hypertension, chorioamnionitis, artificial feeding and male sex) which also contribute to the development of NEC in newborns during prenatal antibiotic therapy, have been identified.

The aim of this study was to determine whether there is an association between antenatal antibi-otic exposure and the incidence of necrotizing enterocolitis (NEC) in low birth weight infants.Study design: A retrospective case-control study was conducted on all infants with NEC who were born between 201 0 and 2020. Medical histories of all infants diagnosed with NEC ≥ Bella IIA stage and corresponding controls without NEC were examined. Maternal and newborn char-acteristics were compared using the Cochran-Mantel-Haenszel method, and logistic regression models were constructed to account for bias.Results. Clinical data were analyzed for 97 matched pairs. The adjusted odds ratio (OR) for pre-natal ampicillin exposure was significantly higher for infants who developed NEC (OR 2.3, 95% CI 1.1,4.8, P = 0.003) than for children in the control group. Infants who developed NEC were more likely to have a history of intrauterine exposure to ampicillin in the immediate prenatal period than infants who did not develop NEC.

In Russia, for more than 10 years, within the framework of national projects, the activities have been carried out aimed at restructuring of the primary and specialized (including high-tech) medical care, as well as strengthening of primary health care directed at early detection of malignant neoplasms. The study was aimed to evaluate the effectiveness of the patient examination rooms for women in improvement of the adjusted cumulative survival of patients with gynecologic malignancies detected actively in 2005–2015 in the Chelyabinsk Region. Using the Population Based Cancer Registry (PBCR) of the Chelyabinsk Region database, the adjusted cumulative survival calculation for patients with cervical cancer (389), uterine corpus cancer (373) and ovarian cancer (161) detected actively in the patient examination rooms of the Chelyabinsk Region (treatment group), as well as for cervical cancer (395), uterine corpus cancer (380) and ovarian cancer (163) detected in patients who sought medical assistance (control group), was performed for the first time. The staging of cervical cancer detected in the examination rooms in 2010–2017 was characterized by the high proportion of I/II stage tumors compared with the rest of patients’ population of the Chelyabinsk Region (an average of 50.8 and 46.1% respectively). For uterine corpus cancer the average proportion was 85.5 and 82.0% respectively, and for ovarian cancers it was 42.0 and 37.4% respectively. Analysis of the PBCR of the Chelyabinsk Region for a 10-year period revealed the 5-year adjusted cumulative survival improvement in the actively detected cervical cancer patients compared to the control group (62.3 and 55.8%) respectively (p = 0.11). In patients with uterine corpus cancer, it was 82.0% for the main group and 70.4% for the control group (p = 0.001). In ovarian cancer patients, no significant differences in the 5-year adjusted cumulative survival were observed (47.5% in the main group, 43.2% in the control group) (p = 0.49). Thus, the patient examination rooms are the effective model of the cancer secondary prevention available in the Chelyabinsk Region.

ASAS health index (ASAS HI) is a comprehensive tool developed on the basis of the international system of ICF (the International Classification of Functioning, Disability and Health) to quantify the health of patients with spondyloarthritis (SPA), including ankylosing spondylitis (AS). ASAS HI is a questionnaire containing 17 questions, each related to a specific ICF pool (pain, emotions, sleep, sexual function, mobility, self-care and communication). ASAS HI additionally includes 9 questions (ASAS EF Item Set) to assess the impact of environmental factors on the health of the patient with SPA. The aim is a Russian translation and adaptation of the ASAS HI (including ASAS EF Item Set). Material and methods. Translation of ASAS HI and ASAS EF Item Set from English into Russian and its adaptation were carried out in five stages: the stage of direct translation; the stage of synthesis of translations and formation of the Russian version; the stage of reverse translation from Russian into English; the stage of comparison of the original English-language questionnaire with the result of reverse translation and the formation of the final Russian-language version; field test. Results and discussion. Three researchers performed an independent translation of ASAS HI (including ASAS EF Item Set), after which the fourth researcher created and agreed on a single Russian version of the questionnaire. Then two volunteers, for whom English is the main language, performed a reverse translation of ASAS HI from Russian into English (reverse translation). An independent researcher has compared the original and the resulting reverse translated English version of the ASAS HI, and then the three translators performed the joint correction of the text of the three questions, differing in English-language versions. The obtained second Russian-language version of ASAS HI (including ASAS EF Item Set) was tested by 10 patients with SPA: AS – 60%; non-radiological axial spondylitis (NR axSPA) – 40%, men – 60%; mean age – 32±12 years; duration of symptoms – 7.5±2.2 years; BASDAI index – 3.39±3.04; ASAS HI – 6,96±3,35.The average time to fill the questionnaire – 2,2±1,18 min. Patients rated the Russian version of the questionnaire as clear, easy to fill in and comprehensively characterizing health problems related to SPA. The results of testing Russian-speaking patients are comparable with the results obtained in testing 206 patients with SPA from 19 non-English-speaking and 4 English-speaking countries (AS – 65%; men – 59.7%; mean age – 42.4±13.9 years; duration of symptoms – 11.2±11.0 years; BASDAI – 3.8±2.3; ASAS HI – 7.1±4.4; filling time – 2.6±1.6 min). Conclusion. During the study translation and adaptation of the Russian version of ASAS HI, which is a tool for comprehensive assessment of health and function of patients with SPA, including AS were performed.

Etanercept (ETC), a soluble tumor necrosis factor-α (TNF-α) receptor, was registered for the treatment of spondyloarthritis in the Russian Federation in 2009. By now, results of prolonged treatment with this drug have been obtained in patients with ankylosing spondylitis (AS). Objective: to evaluate the efficiency and tolerability of long-term therapy with ETC in patients with AS. Subjects and methods. The follow-up included 60 patients with a documented diagnosis of AS (the 1984 New York criteria) and/or axial spondyloarthritis (the 2009 ASAS criteria), high activity (BASDAI >4), who received long-term (at least a year) regular therapy with subcutaneous ETC 50 mg weekly. Its effect was evaluated using the ASAS criteria. Results and discussion. ETC was the first TNF-α inhibitor used in 29 (48%) patients, including 22 (76%) patients who achieved partial remission; 7 (24%) patients who showed ASAS40 improvement. One patient was observed to have hepatotoxicity (alanine aminotransferase elevation to 72 U/l), therefore the drug was discontinued. 31 (52%) patients were switched to ETC after infliximab (n=24) or adalimumab (n=7) due to their poor tolerance and/or loss of effect. At the same time, ETC became the second anti-TNF-α drug in 21 (35%) patients and the third one in 10 (17%). During the therapy, 21 (68%) patients switched to ETC were noted to have ASAS40 improvement; 9 (29%) patients had partial remission. The insufficient effect of the drug was observed only in one patient (3%), in whom ETC was the third TNF-α inhibitor. The tolerability of ETC was generally satisfactory after switching from anti-TNF-α monoclonal antibodies (mAbs). Three patients developed de novo psoriasis that required therapy discontinuation in one patient; another male patient developed uveitis for the first time. In one female patient with AS associated with Crohn’s disease with loss of mAb effect, ETC became the third anti-TNF-α drug, during therapy with which there was no exacerbation of Crohn’s disease. The drug was well tolerated and highly effective in 8 patients, in whom ETC treatment was initiated at the age of 60 years and older: 6 (75%) achieved partial remission, 2 (25%) had ASAS40 improvement. Nine patients with previous and/or latent tuberculosis had no exacerbation of this disease during ETC therapy. Conclusion. During regular therapy with ETC, more than half of patients (52%) achieved partial remission according to the ASAS criteria, while this was more frequently achieved when the drug was used for the first time (76%) than when mAbs were switched to ETC (29%). Discontinuation of the latter due to adverse events was required only in 2 (3%) patients.

Relevance.Modern inactivated culture vaccines against tick-borne encephalitis (TBE) with at least 70% of the population living in the natural foci of the FE give a high epidemiological effect. Unresolved issues are the simplification of the cumbersome vaccination scheme, the optimal number of revaccinations, the protective titer of antibodies against the Siberian subtype of the TBE virus dominant in Russia.Goalof this work is to study the state of postvaccinal immunity in the population of the highly endemic area of the Trans-Urals.Materials and methods. 1381 blood serum of the population vaccinated from 3 to 13 times with vaccines was studied: unconcentrated culture inactivated from strain No. 205 of the TBE virus produced by «Virion», Tomsk, «EnceVir» produced by «Microgen», Tomsk, produced by Chumakov Federal Scientific Center for Research and Development of Immuneand-Biological Products of Russian.To identify specific antibodies – IgG, IgM, antigen of TBE virus, sets of reagents of ELISA from «Vector-Best» were used. Neutralizing activity of sera was determined by the index of neutralization index with 4 strains of the Siberian subtype of TBE virus.Results.The immune layer among the vaccinated population in 10 districts of the Kurgan region, which differ in epidemiological tension, ranges from 69.9% to 94.6%. The intensity of humoral immunity varied according to IgG titers in ELISA from 1: 100 – 1: 200 to 1: 3200 (rarely 1: 6400). The duration and intensity of immunity depends on the number of vaccinations and the number of missed remote revaccinations. Preservation and intensity of immunity with reliability P = 95%, higher in persons vaccinated 6–10 times compared with the group of vaccinated 3 times. In persons who had 4–8 booster dose of vaccine, the immunity persisted for 15–19–36 years with an IgG titer of not more than 1: 100. The neutralizing activity of the sera of vaccinated individuals with antibody titers from 1:100 to 1: 6400 was studied for the Siberian subtype of BCE. The degree of protection of the vaccinated population against the doses of the virus found in individual mites is determined. From the doses of the virus, 57% of the vaccinated population are most often found in mites, and from the dose of 105– 8%. Recommendations are proposed on the tactics of revaccination of the population, depending on the level of immunity.

Extraskeletal manifestations (ESMs) are commonly observed in ankylosing spondylitis (AS). The available data on the association of ESMs with the inflammatory activity and other clinical parameters of AS are contradictory. Objective : to assess the association of ESMs with the inflammatory activity and other manifestations of AS. Patients and methods . The investigators of the V.A. Nasonova Research Institute of Rheumatology examined a total of 452 patients (363 men and 89 women) diagnosed with AS meeting the New-York criteria (1984). The patients' median age was 31.5 [24; 41] years; median disease onset age, 19.5 [15; 23] years; and disease duration, 11.5 [7; 18] years. HLA B27 was identified in 442 (97.7%) patients. In addition to standard laboratory and instrumental examinations, 172 patients underwent transthoracic echocardiography; Rehberg's test, if indicated; IgA test; histological examination of subcutaneous fat tissue or duodenal mucosa for amyloid; renal ultrasound; colonoscopy; and consultations by an ophthalmologist, a dermatologist, a nephrologist, an urologist, and a gastroenterologist. Uveitis, cardiac involvement (cardiac conduction disturbance, aortic and valvular changes), inflammatory bowel disease (IBD), glomerulonephritis, and psoriasis were considered to be ESMs. The latter were detected in 218 (48%) of the 452 patients; there was uveitis in 140 (30%), cardiac conduction disturbance in 61 (13.4%), psoriasis in 17 (3.7%), IBD in 16 (3.5%), nephritis in 16 (3.5%), and aortic and valvular changes in 71 (41.2%) of the 172 patients. The groups of patients with ESM (n = 218) and without ESM (n=234) were compared with regard to the onset age of AS, the presence of HLA- 27, peripheral arthritis, coxitis, enthesitis, syndesmophytis, fever, anemia, the need for biological agents (BAs) and/or systemic glucocorticoids (GCs), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and erythrocyte sedimentation rate (ESR). Results. The ESM and non-ESM groups were matched for gender, age, duration of AS, and the presence of HLA-В27. No significant differences were found in ESR, BASDAI, and the frequency of coxitis, enthesitis, and syndesmophytis in the spine. The ESM group versus non-ESM group was significantly more frequently observed to have peripheral arthritis in 148 (67.8%) of the 218 patients and in 70 (33.2%) of the 234 patients, respectively (p

The paper gives the definition of remission in axial spondyloarthritides (axSpA), which has been developed by the Spondyloarthritis Study Group of Experts. The work used the Delphi technique. At stage 1, based on the analysis of the data available in the literature and on their own clinical experiences, the experts proposed some variants of the definition of remission and ways of its evaluation in patients with axSpA. At Stage 2, the definitions that had received at least 80% of the votes via anonymous voting were selected and adopted without further discussion. Those that had received an equal number of votes were reconsidered and additionally discussed; then there was repeat voting, by choosing the final definition. As a result of their discussion, the experts formulated the definitions of clinical laboratory and magnetic resonance imaging (MRI) remissions. They proposed the following remissions in axSpA: drug and drug-free, clinical laboratory, and MRI remissions, as well as a remission in the presence and absence of structural changes in the locomotor system, as evidenced by imaging techniques. Criteria for clinical laboratory remission and basic tools for its evaluation that can be used in real clinical practice and researches have been elaborated.

The paper gives recommendations for the drug therapy of axial spondyloarthritides, which have been developed by the Spondyloarthritis Study Group of Experts. The recommendations describe the patient management tactic in the most common clinical situations, which is aimed at maximizing the efficacy and safety of treatment.

Involvement of the aorta and heart valves in ankylosing spondylitis (AS) is a manifestation of the systemic inflammatory process. Data on the frequency, clinical significance, and evolution of these manifestations are controversial. Objective : to estimate the time course of echocardiographic (EchoCG) changes in the aorta and heart valves from the results of a prospective follow-up study of patients with AS. Subjects and methods. In 2008 to 2015, the V.A. Nasonova Research Institute of Rheumatology followed up 45 patients (35 men and 10 women) with documented AS that was consistent with the modified New York criteria and the original EchoCG changes in the aorta and heart valves. All the patients underwent transthoracic echocardiography at baseline and after 1–5 years. At baseline, there was aortic root dilatation (>37 mm) in 15 patients, thickening of the aortic walls and aortic valve (AV) cusps in 21 and 32 patients, respectively, as well as thickening of the mitral valve (MV) cusps in 15, and valve prostheses in 5 patients (2 had AV and MV prostheses). Aortic regurgitation (AR) was recorded in 19 patients (grades 1–2 AR in 15 patients and grades 3–4 in 4 patients); grades 1–2 mitral regurgitation (MR) was seen in 20 patients. Ten patients had subaortic pectinate thickening (SPT) in the aortomitral junction area. Of the 45 patients, 16 took biological agents (BA); 29 received traditional therapy, including 14 patients who used nonsteroidal anti-inflammatory drugs, 11 and 4 patients had sulfasalazine and methotrexate, respectively. Results and discussion. Repeated examinations revealed negative changes in 27 (60%) of the 45 patients. Progressive aortic dilatation (1 to 6 mm) was found in 12 (80%) of the 15 patients; dilatation appeared during follow-up in 2 patients. Fourteen patients were noted to have negative valve changes: the emergence of cusp thickening in the valves (that in AV and MV in 9 and 4 patients, respectively; both in 1 patient). Four patients underwent valve replacement: 3 and 1 patients underwent AV and MV replacements, respectively. Ten of the 19 patients were observed to have AR progression by 2 grades in 2 (10.5%) patients and by one grade in 8 (42.0%) patients. MR progression by one grade was noted in 6 (30.0%) of the 20 people. A negative correlation was found between BA therapy and aortic dilation progression (r = -0.329; p = 0.03). SPT appeared in 3 patients. Of the 10 patients who had a baseline SPT, its reduction (8 to 3.5 mm) was seen in one patient; complete regression was identified in two patients; all received BAs. Thus, pathological changes in the aorta and heart valves in AS are progressive in most patients. SPT may regress, which reflects apparently a reduction in the severity of active inflammation of the aortic root. Active anti-inflammatory treatment may play a protective role in the progression of aortic dilatation.

The paper gives the recommendations for the assessment of disease activity and functional status in patients with ankylosing spondylitis in clinical practice, which have been developed by experts, by taking into account international and Russian experience in managing these patients.

Ankylosing spondylitis (AS) is a systemic inflammatory disease involving not only the skeleton, but also other organs. The data on the frequency and clinical significance of extraskeletal manifestations are contradictory. Objective: to assess the frequency and severity of extraskeletal manifestations (ESMs) of AS in the authors' own clinical practice. Subjects and methods. 452 patients (363 men and 89 women) with AS fulfilling the 1984 relevant New York criteria were examined at the V.A. Nasonova Research Institute of Rheumatology in 2005 and 2014. The patients' median age was 31.5 [24; 41] years; median disease onset age, 19 [15; 23] years; disease duration, 11 [7; 18] years; HLA B27 was identified in 442 (97.7%) patients. In addition to standard laboratory and instrumental examinations, transthoracic echocardiography was performed in 172 patients. Rehberg's test, IgA test, histological examination of subcutaneous fat tissue or duodenal mucosa for amyloid, and renal ultrasound were made if there were urinary abnormalities and elevated creatinine levels. If indicated, there were consultations by an ophthalmologist with an appropriate instrumental examination (with evidence of uveitis in the history), a dermatologist, a nephrologist, an urologist, a gastroenterologist, and a endoscopist. Uveitis, cardiac involvement (conduction disturbance, aortic and valvular changes), inflammatory bowel disease (IBD), glomerulonephritis, and psoriasis were borne in mind as ESMs. The absolute number and percentage of patients having any ESM over the follow-up period were estimated. The number of exacerbations per year and that of complications were taken into account when evaluating uveitis; the magnitude of valvular regurgitation and the presence of prosthetic valves and a pacemaker were considered when assessing cardiac damage; the total body surface area (BSA) and the psoriasis areas and severity index (PASI) were estimated in psoriasis; the presence and stage of chronic kidney disease (CKD) and/or macrohematuria were kept in mind in nephropathy; when evaluating IBD, the Harvey–Bradshaw index (HBI) was determined on the basis of a stool frequency, the presence of blood in the stool, abdominal pain, and general well-being. Results and discussion. ESMs were detected in 218 (48%) of the 452 patients. Uveitis was present in 140 (30%) patients; in one-fourth of them, it relapsed frequently: three or more exacerbations per year and more than 10 during the disease; 41 (29%) patients had uveitis complications accompanied by visual impairment. Cardiac conduction disturbance was revealed in 61 (13%) patients. Five of them underwent pacemaker implantation. 71 (41.2%) patients were found to have aortic and valvular changes, including aortic root dilatation/thickening in 60 (34.8%) patients and aortic/mitral valve leaflet thickening in 63 (36.6%). Grades 3 and 4 valvular regurgitation was noted in 10 (5.8%) patients; valve replacement was carried out in 9 (5.2%) cases. Nephritis was diagnosed in 16 (3.5%) patients, 4 of them had Stage 2 or above of CKD. Psoriasis was present in 17 (3.7%) patients; 2 of them had severe psoriasis (BSA >10%). IBD (ulcerative colitis or Crohn's disease) was diagnosed in 16 (3.5%) patients, including 4 who showed a severe course. 79 (36%) patients were observed to have a concurrence of two or more ESMs; that of uveitis and heart disease was most commonly seen. Conclusion. ESMs are observed in nearly half (48%) of the patients with AS and can be concurrent; the most common ESMs of AS are uveitis, aortic root and heart valve lesions, and cardiac conduction disturbance. ESMs worsen the course and prognosis of AS.

Relapsing uveitis is a serious problem for patients with ankylosing spondylitis (AS). Tumor necrosis factor- α inhibitors significantly reduce the frequency of uveitis attacks in AS patients, but they are not always available. In this connection, it is appropriate to evaluate the effect of traditional disease-modifying antirheumatic drugs on the course of uveitis in AS. Objective: to compare the frequency of uveitis attacks in AS during combined therapy using sulfasalazine (SULF) and nonsteroidal anti-inflammatory drugs (NSAIDs) versus monotherapy with NSAIDs. Subjects and methods. A total of 111 patients with significant AS who had at least one uveitis attack during the disease were examined. 49 subjects received combined therapy including SULF 2 grams daily and NSAIDs for at least 1 year. Six of the 49 patients were noted to have frequently relapsing uveitis (above 3 episodes yearly); 43 had no more than 3 ones per year. The remaining 62 patients took NSAIDs only throughout the follow-up period. Nine of them had an average of 3 uveitis attacks per year; 53 had no more than 3 ones per year. Out of the 49 patients receiving combined therapy with NSAIDs and SULF, 23 took NSAIDs only at least 1 year before SULF use; 10 of them were observed to have frequent relapses in that period and 13 had three or fewer episodes. Results and discussion. The entire group showed an average of 2.06±2.04 uveitis attacks per year during monotherapy with NSAIDs and 1.41±1.83 attacks yearly during combined therapy with NSAIDs and SULF (p = 0.08). Among the patients with less than 3 uveitis attacks per year, the mean number of episodes was significantly fewer during combined therapy than during NSAID monotherapy: 0.99±0.87 and 1.37±0.91, respectively (p = 0.04). Among those with frequently relapsing uveitis (more than 3 attacks per year), the mean number of episodes yearly was not significantly different during NSAID monotherapy and combined therapy: 5.7±2.5 and 5.5±2.7, respectively (p = 0.9). In a subgroup of patients receiving sequentially NSAID monotherapy and combined therapy with NSADs and SULF, 13 patients with three or fewer baseline attacks per year displayed a significant reduction in the frequency of episodes from 1.92±0.96 to 0.4±0.44 (p = 0.00003). During combined therapy versus monotherapy, 10 patients with frequently relapsing uveitis (over 3 episodes yearly) exhibited an insignificant reduction in the number of relapses from 5.9±3.02 to 5.33±1.1 (p = 0.6). Conclusion. Combined therapy with SULF and NSAIDs does not substantially affect the frequency of uveitis episodes in AS patients with frequently relapsing uveitis (above 3 attacks per year), but significantly reduces the number of episodes among patients with its mild course (less than 3 attacks yearly).

The paper gives the draft guidelines elaborated by the Expert Spondyloarthritis Diagnosis and Treatment Group by order of the Association of Rheumatologists of Russia. The guidelines include the essentials of how to use nonsteroidal anti-inflammatory drugs in axial spondyloarthrititides, including ankylosing spondylitis, contain instructions for how long they should be administered, and describe possible patient management tactics in the most common clinical situations and a preferential algorithm for evaluating the efficiency and safety of treatment.

The paper provides guidelines for the use of tumor necrosis factor- α (TNF- α ) inhibitors in the treatment of patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis. It gives data on the efficacy of TNF- α inhibitors in patients with non-radiographic axSpA. By using international and Russian guidelines, the authors lay down indications for this therapy and criteria for evaluation of its efficiency and safety.

At present, there are a number of unsolved problems associated with unawareness of the causes and ways to prevent the inefficacy of tumor necrosis factor-α inhibitors. Objective: to study the causes of secondary inefficacy of infliximab (INF), by analyzing its concentrations and antidrug antibody levels in the serum of ankylosing spondylitis (AS) patients receiving long INF, as well as a possibility to overcome its secondary inefficacy through plasmapheresis. Subjects and methods. 54 patients with active AS (BASDAI > 4) underwent regular long-term (1-to-10-year) treatment with INF 5 mg/kg according to the standard scheme. During the therapy blood samples were taken before a regular INF infusion to quantify the levels of antibodies to the drug and its concentration. According to the efficiency of the drug, two groups were formed: 1) 27 (50%) patients with INF inefficacy (an exacerbation occurred 2–4 weeks after infusion); 2) 27 patients with drug efficacy. The levels of anti-double stranded DNA antibodies and antinuclear factor were estimated in 27 patients to investigate a relationship between the immunogenicity of INF and the presence of autoantibodies in its secondary inefficacy. A plasmapheresis session was carried out in 5 patients before a regular IFN infusion. Results and discussion. Anti-INF antibodies were found in 28 (52%) patients, these being more common in the patients with drug inefficacy than in the others (67 and 37%, respectively; p < 0.05). In the patients with INF inefficacy, anti-INF antibody levels were significantly higher than in those with preserved drug effect (18.33 and 4.67 U/ml, respectively; р < 0.05). Moreover, the serum concentration of INF was not significantly different in these groups (1.6 and 2.96 μg/ml). There was an inverse correlation between INF concentrations and anti-INF antibodies (r = -0.7; p < 0.05). The level of autoantibodies did not correlate with that of anti-INF antibodies. Following plasmapheresis, the level of anti-INF antibodies dropped in all the patients and the concentration of the drug increased in only three of the five patients; in two of them anti-INF antibody levels were initially low (p < 0.05). Plasmapheresis promoted a short-term restoration of INF efficacy no matter what the baseline level of anti-INF antibodies. Conclusion. The secondary inefficacy of INF may be associated with not only the emergence of its neutralizing antibodies and the reduction in serum drug concentration, but also with other yet unknown causes. There is a need for further investigation of the causes of secondary INF insufficiency and methods for its overcoming.

By the end of the first decade of the 21st century, spondyloarthritis studies have accumulated a certain number of terms that are obsolete, but used by physicians in their everyday speech, on the one hand, and a great variety of different definitions, on the other hand. In January 2014, the first organizational meeting of the Expert Group on Spondyloarthritis, Association of Rheumatologists of Russia, decided that its primary task should be to order the terminology used in this area. The authors primarily collected the terms, which had been already used in medical vocabulary, and then divided them into two categories: obsolete definitions and terms to be finalized and unified. This publication gives guidelines for using the medical terms relevant to spondyloarthritis and separately discusses how to correctly write the term sacroiliitis.

Objective. The risk of AS is associated with genomic variants related to antigen presentation and specific cytokine signalling pathways, suggesting the involvement of cellular immunity in disease initiation/progression. The aim of the present study was to explore the repertoire of TCR sequences in healthy donors and AS patients to uncover AS-linked TCR variants. Methods. Using quantitative molecular-barcoded 50-RACE, we performed deep TCR beta repertoire profiling of peripheral blood (PB) and SF samples for 25 AS patients and 108 healthy donors. AS-linked TCR variants were identified using a new computational approach that relies on a probabilistic model of the VDJ rearrangement process. Results. Using the donor-agnostic probabilistic model, we reveal a TCR b motif characteristic for PB of AS patients, represented by eight highly homologous amino acid sequence variants. Some of these variants were previously reported in SF and PB of patients with ReA and in PB of AS patients. We demonstrate that identified AS-linked clones have a CD8(+) phenotype, present at relatively low frequencies in PB, and are significantly enriched in matched SF samples of AS patients. Conclusion. Our results suggest the involvement of a particular antigen-specific subset of CD8+ T cells in AS pathogenesis, confirming and expanding earlier findings. The high similarity of the clonotypes with the ones found in ReA implies common mechanisms for the initiation of the diseases.

Uveitis is a common extraskeletal manifestation of ankylosing spondylitis (AS) occurring in 20–40% of patients. Most authors underline a favorable prognosis for AS-associated uveitis. Objective: to study features of clinical picture and progression of AS-associated uveitis and to estimate the occurrence of its complications. Subjects and methods. Across-sectional study of 140 patients (98 males and 42 females) with AS, who had at least one uveitis attack over the period of disease and was followed up at V.A. Nasonova Research Institute of Rheumatology during 2008–2012. In addition to standard rheumatologic examination all patients were examined by ophthalmologist. Biomicroscopy, ophthalmoscopy, tonometry, computer-assisted perimetry, ultrasonography (B-scanning) of eyes and, if needed, fluorescein angiography and electrophysiological examination of retina were performed. Localization of uveitis, presence of complications affecting vision, total number of uveitis attacks by the moment of examination, mean number of uveitis attacks per year, correlation between the frequency of attacks and complications, presence of other extraskeletal manifestations and peripheral arthritis were assessed. The total number of uveitis attacks was defined from patients' interviews and respective medical documentation. Mean number of uveitis attacks was calculated as ratio of total number of uveitis attacks to the duration of disease for each patient. In the case of more than two attacks per year uveitis progression was considered refractory. Results. Mean duration of the disease was 17.7±11.03 years. In 19 patients (14%) AS manifested before and in 121 (86%) – after the age of 16 years. HLA-B27 was revealed in 135 (96%) patients, peripheral arthritis – in 43 (30%), whereas other extraskeletal manifestations – in 46 (32%). Early onset of uveitis in first 10 years of the disease was recorded in 81 (58%) patients, after10 years – in 21 (15%). Uveitis was the first clinical symptom of AS in 37 (26.4%) patients. 33 (24%) patients had more than 10 uveitis attacks during the disease, 17 (12%) – more than two attacks per year, whereas 18 (13%) had chronic uveitis. 118 (84%) had localized iridocyclitis, 12 (8%) – panuveitis, 2 (1%) – localized posterior uveitis. 122 (87%) patients had unilateral uveitis, 18 (13%) – bilateral, whereas 45 (36%) – alternating eye lesions (OD-OS). Uveitis complicated with vision impairment was observed in 41 (29%) patients: synechia in 26 (18%), vitreous degeneration – in 20 (14%), cataract – in 32 (23%), glaucoma – in 13 (9%), maculopathy – in 6 (4%), ribbon-like retinal degeneration – in 6 (4%), partial optic nerve atrophy – in 3 (2%). Authors revealed direct correlation between frequency of uveitis attacks and occurrence of synechia, cataract, glaucoma, vitreous degeneration. Conclusion. AS-associated uveitis is predominantly characterized by unilateral iridocyclitis (84%) and the onset in the first 10 years of disease (84.4%); 25% of cases were remarkable for frequent relapses: more than two attacks per year and more than 10 during the period of disease. One third of patients demonstrated vision impairments, and its progression correlated with the frequency of uveitis attacks.

Ankylosing spondylitis (AS) belongs to a group of autoimmune diseases affecting the axial skeleton. Beside the hla-b*27 allele, several other human genes that control the variety processes of immune homeostasis are considered to be associated with AS manifestation in different human populations. Among strong associated non-MHC genes erap 1 encoding the endoplasmic reticulum aminopeptidase 1 isoform was recently identified by single nucleotide polymorphisms (SNPs) meta analysis. In our study we inspected the genetic association of five non-synonymous coding SNPs from erapl with AS in Caucasians. We implemented the SSP-PCR system for precise genotyping of 87 hla-b*27 positive AS patients and 77 hla-b*27 healthy donors from the Russian population. Considerable differences in allele’s frequencies within patients vs control cohort were shown for 3 of 5 SNPs under investigation. Using the EM-algorhitm we reconstructed 3-marker haplotypes that distinguish with high probability two cohorts due to differences in the haplotypes frequencies. In such a way both the sensitive, CCT, haplotype and the protective, TTC, one were predicted. To verify the calculation we determined genuine frequencies of 5-marker haplotypes in AS cohort by haplotyping of individual cDNA samples using improved SSP-PCR primer set. We demonstrated that the frequencies of in silica reconstucted haplotypes and the frequencies of experimentally detected haplotypes are in a good agreement. Frequency of the risk haplotype CCT (rs17482078/10050860/2287987) detected within AS cohort reaches 88%, as well as the frequency calculated by EM-algorhitm.

A work classification of ankylosing spondylitis is presented including such novel concepts as the stage of the disease (instead of sacroiliitis), extra-axial and extra-skeletal manifestations. Modern approaches to the evaluation of disease activity are described Extensive explanations of these notions are presented together with the recommendations on formulation of diagnosis. The advent of new and more eficacious methods of visualization as well as more sensitive and specific criteria for inflammatory nature of back pain are considered The authors modified the traditional criteria for ankylosing spondylitis and developed their version to be verified in clinical practice in this country.

Objective. To analyze and compare clinical, radiological and ultrasonic signs of coxitis in pts with ankylosing spondylitis (AS). Material and methods. 35 pts with AS and clinical signs of coxitis were included. Median age was 26 years, AS duration 9 years, coxitis duration 5 years. 17 pts with AS without clinical signs of coxitis constituted control group. Pain on visual analog scale, hip joint mobility, radiological changes and ultrasonic signs of exudation were assessed. Results. Among the pts with AS prevailed those with the beginning of the disease before 20 years of age (77%). 71% of pts had bilateral coxitis. In 40% of pts coxitis signs during the first years were inconstant. Most frequent radiological signs of coxitis were narrowing of joint space (91,9%), femoral head or/and acetabulum cysts (77,4%), femoral head osteophytes (67,7%). Femoral head deformity (8,1%), partial bone anchylosis (6,5%), marginal bone erosions (3%) acetabulum protrusion (1,6%) were rare signs. Exudation was present in 84% of damaged hip joints. Bone destruction was significantly more frequent in pts with longer duration of AS and coxitis and was associated with more prominent functional disability and higher frequency of exudation. Hip joint exudation frequency and its volume did not influence pain intensity. Radiological changes were revealed in 12 hip joints of 7 pts of control group.

First autologous hematopoietic SCT for ankylosing spondylitis: a case report and clues to understanding the therapy