Chirality-Helicity of Cumulenes: A Non-Scalar Charge Density Derived Perspective

We investigate the presence of helical character and chirality using a vector-based charge density perspective instead of energetic or structural measures. The vector-based perspective of the chemical bonding, constructed using the most preferred direction of charge density accumulation, finds the presence of induced symmetry-breaking for α,ω-disubstituted [4]cumulenes as the end groups are torsioned. The stress tensor trajectories Tσ(s) are used to provide the additional symmetry-breaking required to quantify the degree and nature of the chirality and helical character. We find an absence of chirality for [4]cumulene but a very significant degree of axiality as demonstrated by the purely axial form of the Tσ(s) indicating a lack of helical character. The S-1,5-dimethyl-[4]cumulene contains a very low degree of chiral character but significant axiality(helicity) resulting in a weakly helical morphology of the corresponding Tσ(s). The (-)S(-), (+)S(-) and (+)S(+) conformations of S-1,5-diamino-[4]cumulene contain very significant degrees of both chirality and helical character resulting in helical morphology of the corresponding Tσ(s). The chirality assignments are in agreement with the Cahn–Ingold–Prelog (CIP) classifications for the (-)S(-), (+)S(-) and (+)S(+) conformations of S-1,5-diamino-[4]cumulene. We discuss the consequences for the Tσ(s) in locating chiral character in these molecules in future experiment investigations.

Ultrasound-Verified Peripheral Arthritis in Patients with HLA-B*35 Positive Spondyloarthritis

Background: We aimed to investigate possible association between the HLA-B*35 allele and peripheral arthritis, tenosynovitis and enthesitis. Methods: Ultrasound of peripheral joints and tendons was performed in 72 HLA-B*35 positive patients with preliminary diagnosis of undifferentiated axial form of spondyloarthitis and joint and tendon pain. Patients with other known types of axial and peripheral spondyloarthritis were excluded as well as patients with other known types of arthritis. Results: Pathological changes were found in the joints of 33 (46%) patients and on the tendons in 13 (18%) patients. The most common ultrasound findings were joint effusion and synovial proliferation with positive power Doppler signal grade 1. The most common ultrasound finding in patients with painful tendons was tenosynovitis. A higher disease activity and an increased incidence of elevated CRP (≥5 mg/L) were more often observed in the group with positive ultrasound findings. Conclusion: In this study, we showed that the HLA-B*35 allele could be a potential risk factor for developing peripheral arthritis, but not for tenosynovits and enthesitis in patients with the undifferentiated axial form of spondyloarthritis. This result may influence the follow up of these patients, especially since it gives us an opportunity to consider the use of different types of DMARDs in the treatment of these patients.

Expansion of myeloid-derived suppressor cells in the peripheral blood of patients with ankylosing spondylitis

Expansion of myeloid-derived suppressor cells (MDSCs) due to impaired differentiation of myeloid progenitor cells under conditions of inflammation was described in a number of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes mellitus. Studying the role of MDSCs in ankylosing spondylitis is an important issue, given that increased concentration of proinflammatory mediators in this pathology can also cause myelopoiesis disorders. The aim of present work was to study the quantitative content of MDSC subpopulations in patients with different clinical phenotypes and activity of AS. 37 patients, including 10 patients without peripheral skeletal lesions (axial form) and 27 patients with simultaneous lesions of spine and peripheral joints (peripheral form) were recruited into the study. The control group consisted of 32 age/sex-related healthy donors. Evaluation of granulocytic (LinHLA-DRCD33+CD66b+; G-MDSC), monocytic (CD14+HLA-DRlow/-; M-MDSC) and early-stage MDSCs (LinHLA-DRCD33+CD66b- ; E-MDSC) was performed using corresponding antibodies (BD Biosciences, USA) in the population of peripheral blood mononuclear cells by flow cytometry. In general, the AS patients were characterized by an increased relative and absolute amount of M-MDSC (p = 0.00002 and p = 0.00003, respectively) and G-MDSC (p = 0.0002 and p = 0.0006, respectively). Patient gender, age, and HLA-B27 expression did not significantly affect the content of these cells in peripheral blood. An increase in the median values of M-MDSC was detected both in patients with axial (Ме 5.0 (3.2-6.3) versus 2.4 (1.7-3.5) %; p = 0.001) and peripheral form (Ме 5.0 (3.0-7.0) versus 2.4 (1.7-3.5) %; p = 0.0002) AS. At the same time, the G-MDSC expansion was observed only in patients with involvement of peripheral joints (Ме 0.16 (0.07-0.3) % versus 0.05 (0.04-0.09) %; p = 0.0001). The relative contents of E-MDSC, M-MDSC and G-MDSC in the axial form of AS was in direct correlation with the activity of the disease (R = 0.58, p = 0.02; R = 0.73, p = 0.08 and R = 0.65 p = 0.04, respectively). This relationship was not observed in peripheral form of AS. The data obtained suggest a potential involvement of MDSCs in pathogenesis and phenotypic heterogeneity of AS. Simultaneously, the revealed direct correlation between the MDSC contents and the disease activity suggests a decrease in suppressive activity and/or appearance of pro-inflammatory activity in MDSC, thus requiring further research in the field.

Uveitis – Possible adverse reaction to secukinumab in a patient with rehabilitation treatment for ankylosing spondylitis (case report)

Introduction. Ankylosing spondylitis (AS) is a chronic inflammatory disease that predominantly affects the spine, but also peripheral joints, the major characteristic of the disease being the early involvement of the sacroiliac joint. The most common extra skeletal manifestations are ocular disorders and appear to 25-30% of the patients, being more frequent to HLA B27 positive patients. Episodes of previous acute uveitis, known as iridocyclitis, may precede or may occur during or after inflammatory joint manifestations. Materials and Methods. We present a 41-year-old patient diagnosed 11 years ago with Ankylosing spondylitis, on its axial form, without extra-articular manifestations, periodically treated with anti-inflammatory drugs and balneary treatment, but with inefficient clinic and biological response. Since November 2019, his treatment with Secukinumab, started to improve the clinic and paraclinical symptoms. Secukinumab is a fully human monoclonal antibody, the first care that selectively targets IL-17A, an essential cytokine treatment that produces inflammation, and bone remodeling, characteristic of AS. Results. In January 2020, the patient presents increased pain and redness in the right eye area, subsequently diagnosed as anterior acute uveitis. Conclusions. This anterior acute uveitis, may be an extra-articular manifestation in the context of the natural evolution of the disease insufficiently controlled by the recently introduced therapy, or it may be an adverse reaction to Secukinumab, being known that the optic malfunction is a less common side effect. Keywords: Ankylosing Spondylitis, Uveitis, Secukinumab, extra-articular manifestations, rehabilitation, treatment,

AB0635 HOW ARE NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAID) PRESCRIBED IN AXIAL SPONDYLOARTHRITIS?

Background:For decades, NSAID have been used as the first-line drugs to treat axial spondyloarthritis (ax-SpA). However, the NSAID prescription strategy is not clearly detailed and it varies from one clinician to another.Objectives:The aim of this study was to assess the NSAID prescription modalities adopted in ax-SpA and the differences between these modalities.Methods:This is a descriptive study including 200 cases of ax-SpA fulfilling the ASAS 2009 criteria and diagnosed between January 2000 and October 2019. The demographic and clinical features of the ax-SpA were collected and the modalities of prescription of NSAID were retrospectively assessed.Results:Our population consists of 138 men and 62 women with a mean age of 43,3 ± 11,2 years. The HLA B-27 antigen was present in 50,8% of cases. The ax-SpA was a pure axial form in 67% of patients, associated with peripheral arthritis, enthesitis and dactylitis in 19%, 21,5% and 1,5% respectively.One hundred eighty patients (90%) had been treated with NSAIDs. The NSAIDs used were: the Diclofenac (57.5%), Indomethacin (37.5%), Piroxicam (36%), clecoxib (34%), Naproxen (29.5%) and ketoprofen (13%). Seventy-three patients (36.5%) had used at least 3 NSAIDs.Among the 180 patients treated with NSAID, 88 patients (48,8%) were treated with conventional synthetic DMARDs (csDMARDs) in association with NSAID: Salazopyrine (43,3%) and Methotrexate (13,3%). Seventy-one patients (39,4%) had necessitated the use of anti-TNF alpha.NSAIDs were used continuously in 115 patients (63.8%) and the maximum dose of NSAIDs was used in 78 patients (43.3%). By comparing patients who used maximum doses of NSAIDs and those who used NSAID continuously with other patients, we noticed that the use of biological treatments was more frequent in those groups (p = 0,01 and p=0,004 respectively).In addition, while comparing the group of patients co-treated with csDMARDs with other patients treated with NSAID on monotherapy, we noted that this group of patients had more arthritis (p<0,0001), enthesitis (p=0,02), psoriasis (p=0,04) and necessitated more biological treatments (p=0,01).Conclusion:Our results suggest that maximal doses and/or continuous prescription of NSAID were mainly used if there was no response to that treatment. The csDMARDs were more prescribed if there were peripheral manifestations or psoriatic arthritis and those forms were also more candidates to biological treatments.References:[1]Wang R, et al. Arthritis Rheumatol Hoboken NJ. 2019;Disclosure of Interests:None declared