Treatment algorithms for systemic sclerosis have not been completely developed. Effectivity of medications are usually used in clinical practice has a low level of evidence. Therefore, it is necessary to find a new treatment approaches for this nosological form. In the paper described clinical case of olokizumab treatment in a patient with diffuse systemic sclerosis with interstitial lung disease, polyserositis, severe microcirculatory alterations.
Idiopathic recurrent pericarditis (IRP) and adult-onset Still's disease (AOSD) are polygenic autoinflammatory diseases, in the pathogenesis of which pro-inflammatory cytokines from the interleukin-1 superfamily play a central role.Aim. To compare serum concentrations of proinflammatory cytokines and glycosylated ferritin (GF) in patients with IRP and AOSD during an exacerbation.Material and methods. The study included 15 patients with AOSD, 15 — IRP. The diagnosis of AOSD was established using the Yamaguchi criteria (1992). IRP was diagnosed in accordance with the 2015 European Society of Cardiology on the diagnosis and management of pericardial diseases. Blood sampling from all patients was carried out during the recurrence period prior to the anti-inflammatory therapy initiation. The serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18), procalcitonin, total ferritin and GF was assessed. The results obtained were compared with levels of biochemical parameters, high-sensitivity C-reactive protein (CRP), as well as with white blood cell (WBC) and neutrophil counts.Results. The median age in the AOSD group was 28 years, and the IRP — 55 years. An increase WBC count >10*109/L was detected in 10 and 9 patients in the AOSD and IRP groups, respectively. The concentration of CRP was increased in all patients and did not differ in the study groups (p=0,836).The highest values of ferritin and GF levels were found in the AOSD group (1416 ng/ml vs 408 ng/ml, p=0,008) and (12% vs 33,9%, p=0,067), respectively. In both groups, increased concentrations of IL-6 and IL-18 were determined. In the AOSD group, the concentration of IL-18 was higher than in the IRP group (2114 pg/ml vs 161,5 pg/ml, p<0,001). IL-6 concentrations in the study groups did not differ (33,9 pg/ml vs 24,9 pg/ml, p=0,4). IL-1β serum concentration in all subjects corresponded to normal values.Correlation analysis in the AOSD group revealed a direct relationship between the IL-18 and ferritin concentrations (rs=0,73, p=0,03).Conclusion. The study established a similar pattern of changes in inflammatory biomarkers in patients with AOSD and IRI. The most informative marker of inflammation was IL-18.
Proliferation and hyperactivation of B-lymphocytes in the salivary glands is a feature of primary Sjцgren's syndrome (pSS). Detection in saliva of proteins synthesized by B-lymphocytes may be important in the diagnosis of this disease.Objective: to evaluate the diagnostic value of measuring the concentration of immunoglobulin free light chains (FLC) in saliva in patients with pSS.Material and methods. The cross-sectional study included 24 patients with pSS over the age of 18 years. PSS was diagnosed according to the 2016 ACR/EULAR classification criteria. The control group consisted of 11 healthy volunteers. Blood-salivary glands histohematic barrier permeability ratio for albumin, FLC was measured. Quantitative determination of FLC and in blood and saliva was performed by enzyme immunoassay. An immunohistochemical study of biopsies of minor salivary glands (MSG) was carried out with a quantitative assessment of CD3+, CD4+, CD8+, CD20+, CD21+, CD68+, CD138+ cells. The Mann–Whitney U-test was used to compare quantitative traits. Identification of diagnostic thresholds for the concentration of FLC in saliva for the diagnosis of pSS was carried out using the ROC analysis method. An operating characteristic curve was plotted, the area under the curve, indicators of diagnostic specificity, diagnostic sensitivity, and diagnostic accuracy were calculated.Results and discussion. The obtained values corresponded to the low permeability of the histohematic barrier of the salivary glands for albumin and FLC in patients with pSS and healthy individuals. The median concentrations of FLC ê and ë in the saliva of patients with pSS and healthy volunteers were 1.08 [0.58; 1.91], 1.038 [0.55; 2.03] mg/l and 0.36 [0.32; 0.54], 0.35 [0.21; 0.52] mg/l, respectively. The concentration of FLC in the saliva of patients with pSS was statistically significantly higher than in the control group (p<0.01). The amount of FLC ê and ë in saliva correlated with the rate of unstimulated saliva flow: rs=-0.483 (p=0.02), rs=-0.491 (p=0.017), respectively.A relationship was found between the concentration of ê-chains in saliva and the specific number of CD138+ cells: rs=0.733 (p=0.025). Statistically significant correlations between the concentration of ë-chains and the number of mononuclear cells in the MSG have not been established.Based on the results of ROC analysis, diagnostic thresholds for FLC concentrations in the saliva of patients with pSS were determined. Concentrations of ê- and ë-type FLC in saliva of 0.56 and 0.68 mg/l correspond to area under the curve values of 0.84 (95% confidence interval, CI 0.69–0.98) and 0.83 (95% CI 0.71–0.97), sensitivity 79.2% (95% CI 59.5–90.8) and 75% (95% CI 55.1–88), specificity 81.8% (95% CI 52.3–96.8) and 90.9% (95% CI 62.3–99.5), respectively.Salivary FLC concentrations were compared in patients with pSS receiving and not receiving glucocorticoids (GC). The groups did not differ in a statistically significant way in terms of clinical and laboratory parameters. The median daily dose of GC was 10 [5; 10] mg in prednisolone equivalent. There were no significant differences between the concentrations of saliva FLC in patients of these groups.Conclusion. Salivary-fixed FLCs are most likely produced by cells localized in the stroma of the salivary glands. Determination of the concentration of FLC in saliva can be proposed as a diagnostic test for the pSS. The concentration of free ê-chains in saliva can be considered as a surrogate marker of benign B-cell proliferation in the MSG. Therapy with low and medium doses of GC in pSS does not affect the concentration of FLC in saliva.
Background:Adult onset Stills disease (AOSD) and Idiopathic recurrent pericarditis (IRP) are currently considered auto-inflammatory diseases. Common features of these disorders are symptoms such as fever, leukocytosis, serositis, increased acute phase reactants.Diagnosis of IRP is based on ESC 2015 diagnostic criteria, while AOSD is defined according to 3 sets of classification criteria. A detailed study shows that modern criteria for these nosologies overlap and do not allow distinguishing one from the other.Objectives:We have not found any data on the comparison of the two groups in the literature. We compared the two groups of patients according to several parameters, such as clinical features, laboratory testing, genetic analysis to identify common patterns.Methods:We enrolled 22 newly identified subjects (13 patients with AOSD, 9 patients with IRP) to our prospective, monocenter study. The mean age of patients with AOSD was 31 [22; 39], the mean age of patients with IRP was 46 [35;54]. Blood sampling in all patients was performed in the flare.We quantified the serum levels of ferritin and its glycosylated fraction in both groups. Mutations of the MEFV, TNFRSF1A genes were studied. As more sensitive imaging methods for lymphadenopathy and serositis, we performed the following instrumental studies for all patients: transthoracic echocardiography, ultrasound of the abdominal cavity and pelvis, chest high-resolution computed tomography.Results:One subject with a heterozygous missense variant was found in exon2 of the MEFV gene (E148Q) in the IRP group. The patient was excluded from our study. Elevated white blood cell (WBC) count and C-reactive protein (CRP) were observed in all patients in 2 groups, however, the level of WBC greater than 10,000/mm3was found only in 10 patients from the AOSD group and 5 – from the IRP. Elevated ferritin level in both groups was detected. The number of subjects with high level of ferritin in the AOSD group reached 12 (n=13), in the IRP group – 7 (n=8).The ferritin level appeared to be more significant in the AOSD group compared to the IRP group (1521 ng/ml vs 408 ng/ml p=0.0159) Figure 1.In turn, lower glycosylated ferritin was recorded in 9 patients with AOSD (n=13), and 7 – with IRP (n=8). We have demonstrated a more significant decrease of glycosylated ferritin level in patients with AOSD in comparison to patients with IRP, which amounted (11% vs 37% p = 0.0286) reference value (38.6%-84.7%). Figure 1.Abnormal liver function tests were found in the majority of patients with AOSD and IRP (61% vs 75%).We have also shown that, if the patient had pericardial effusion, the fluid was present in the pleural cavity, regardless of the group.The number of AOSD patients with polyserositis was 5 (n=13).Other symptoms are presented in Table 1Table 1Symptom and signAOSD (n=13)IRP (n=8)CRP mg/L, mean, %123 [69;164], 100%151[65; 226], 100%Pericarditis38%100%Pleuritis38%100%Leukocytosis ≥10,000/mm377%62%Abnormal liver function tests61%75%Fever >39 °C100%100%Rush77%0 %Arthralgia100%75%Arthritis, lasting 2 weeks or longer100%12.5%Sore throat54%0%Recent lymphadenopathy85%25%Hepatomegaly or splenomegaly54%62%Elevated ferritin92%87%Glycosylated ferritin ≤20%69%25%Conclusion:The level of ferritin in the IRP group was lower, which can be explained by a less generalized process, the absence of such symptoms as arthritis, rash, splenomegaly.Diagnostic and classification criteria of both disorders do not allow distinguishing between the diseases.There might be no differences between the diseases; further research (on more representative groups) is needed. We consider the comparison of the gene-expression analysis in these patients to be of great importance.Disclosure of Interests:None declared
Background:Primary Sjogren’s syndrome (pSS) is frequent nosological forms among the diffuse connective tissue diseases. Histological examination of the minor salivary gland (MSG) is important diagnostic method. The currently established histological criteria for pSS indicates 61.2-93.7% sensitivity and 61.2-100% specificity respectively, which makes the search for additional hallmark highly relevant. Immunohistochemical study of MSG is the most appropriate for this purpose.Objectives:To study of the qualitative and quantitative compositions of cellular subpopulations minor salivary gland mononuclear foci as additional histological criteria of pSS.Methods:The study included 56 patients with a definite diagnosis of pSS according to the criteria of ACR\EULAR 2016. The control group consisted of 19 healthy volunteers. The biopsy of the minor salivary gland was performed for all the subjects, followed by an immunohistochemical study to evaluate the expression of CD3, CD4, CD8, CD20, CD21, CD68, CD138. A statistical analysis of the data obtained during the study was carried out using the SPSS 23 statistical software for Windows (IBM, United States of America). Diagnostic threshold for each biomarker was determined by ROC analysis. Operating characteristic curve, area under the curve (AUC), specificity, sensitivity, diagnostic accuracy (DT), diagnostic thresholds (DP), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were also calculated. The construction of classification models, including several markers, was performed using linear discriminant analysis.Results:The largest AUC were observed in CD3 - 0.795 [95% confidence interval (CI) 0.697 - 0.893] and CD20 - 0.796 (95% CI 0.698 - 0.894), which at the specified DP corresponded to the sensitivity of 67.9% (95% CI 54.04 - 79.71) and 71.4% (95% CI 57.79 - 82.7), specificity of 95% (95% CI 73.97 - 99.87) and 95% (95% CI 73.97 - 99.87).The CD21 marker was detected only in the PSS group. AUC for this biomarker was 0.652 (95% CI 0.525 - 0.778), sensitivity - 30.4% (95% CI 18,78 - 44.1), specificity - 100% (95% CI 82,35 - 100).Using the method of discriminative analysis, we designed classification models that included various combinations of the markers under study. The combination of the decimal logarithms CD3 and CD68 had AUC 0.873 (95% CI 0.794 - 0.953), sensitivity - 76.8% (95% CI 63.58 - 87.02), specificity - 95% (95% CI 73.97 – 99.87).Conclusion:CD3 and CD20 can be considered as additional histological criteria for pSS. CD21 was observed only in patients with pSS. The combined quantitative assessment of CD3 and CD68 had a greater diagnostic value compared to CD3 and CD68 separately. Disclosure of Interests:None declared
Background:Patients with primary Sjogren’s syndrome (pSS) exhibit biological signs of B cell activation such as serum polyclonal hypergammaglobulinaemia, increased levels of free light chains (FLC) and positivity for autoantibodies. B-cells may comprise up to 50% cells of lymphocytic infiltrates in salivary glands of patents with the disease. For that reasons measuring saliva B-cells products might have diagnostic value in pSS.Objectives:To evaluate relationships between saliva free light chains concentration and clinical, immunological, histological parameters in patient with pSS.Methods:Saliva and blood FLC concentrations were measured in patient with pSS (n = 24) and healthy volunteers (n = 11). Patients fulfilled the ACR/EULAR 2016 criteria of pSS. Saliva collected during assessment unstimulated salivary flow was used for analysis. Quantitative assessment of CD3+, CD4+, CD8+, CD20+, CD21+, CD68+, CD138+ cells was performed in minor salivary glands of 9 patient by immunohistochemistry. Cells quantity was calculated in 4 mm2 (area of section).Results:FLC concentration in saliva of pSS patients was higher than in healthy volunteers (p<0,01). Medians of saliva κ - and λ – free light chains concentrations in patients and healthy persons were 1,08 mg/L [25-;75- percentiles 0,58;1,91], 1,038 mg/L [0,55;2,03] and 0,36 mg/L [0,32; 0,54], 0,35 mg/L [0,21; 0,52] respectively. Median of saliva κ: λ chains ratio in pSS patient was 0,94 [0,6;1,5]. The ratio didn’t differ from healthy persons (p=0,24). Saliva κ – and λ – free light chain concentrations in patient with pSS correlated with patients age (rs= 0,51, p=0,033 and rs=0,43, p= 0,011, respectively) and unstimulated salivary flow (rs= -0,48, p=0,02 and rs=-0,49, p= 0,017, respectively). Concentration of κ – free light chain correlated with number of CD138+-cells (rs= 0,733, p=0,025). Interesting that saliva λ – free light chain concentration didn’t correlate with quantity of plasmatic cells.Conclusion:Measuring saliva FLC concentration might be offered as diagnostic marker of pSS. Concentration κ – free light chain can directly mirror the glands quantity of plasmatic cells.References:[1]Nocturne, Gaëtane; Mariette, Xavier (2018): B cells in the pathogenesis of primary Sjögren syndrome. In Nature reviews. Rheumatology 14 (3), pp. 133–145. DOI: 10.1038/nrrheum.2018.1.Disclosure of Interests:None declared
BackgroundSystemic lupus erythematosus (SLE) and primary Sjogren’s syndrome (pSS) are chronic autoimmune diseases with complex pathogenesis. T-lymphosytes are known to be prime effectors of autoimmune diseases, while B-lymphosytes play a key role as sources of antibodies and antigen presenting cells. Considering the implications of T- and B-cells in the pathophysiology of SLE ans pSS, the assessment of their distribution in the blood could be helpful in the complex process of determining a precise diagnosis.ObjectivesThe study aimed to compare composition of peripheral blood T- and B-cell subsets and investigate their diagnostic utility in patients with SLE and pSS.MethodsThe study was performed with 37 patients suffering from SLE, 57 patients with pSS, and 49 apparently healthy volunteers (HVs). The diagnosis of SLE was performed according to the 2019 EULAR – ACR classification criteria, the diagnosis of pSS- according to the 2016 EULAR – ACR criteria. 11 patients in pSS group met the criteria for both pSS and SLE. The relative distribution and percentage of T- and B-cell subsets were evaluated by flow cytometry. T helper (Th) and cytotoxic T-cell subsets (Tcyt) were identified by using CD3, CD4, and CD8 antibodies. Regulatory T cells (Tregs) were characterized by the expression of CD3, CD4, and high IL-2R alpha chain (CD25high) levels. All peripheral blood B-cells were identified by using CD19 antibody, detection of subpopulations of B cells based on expression of IgD, CD38, CD27. The absolute and relative values of B-lymphocyte subpopulations were evaluated using three main classifications: based on IgD / CD38 expression (classification Bm1-Bm5), co-expression of IgD / CD27 and CD38 / CD27. The statistical analysis of data was performed with STATISTICA Version 12.0 Inc. Method of discriminant analysis was performed to evaluate diagnostic utility of relative values of T- and B-cell subsets.ResultsIn the discriminant model the top significance was documented while assessing the percentage of naive B-cells (Bm1, IgDdimCD38low), germinal center B-cells (Bm 3+Bm4, IgDlowCD38hi), naive B-cells (IgDdimCD27low), unswitched memory B-cells (IgDdimCD27dim), naive mature B-cells (CD27dimCD38low), transient B-cells (CD27lowCD38hi), all T-cells (CD3hi), Tregs (CD3hiCD4hiCD25hi), Tcyt (CD3hiCD8hi) and Th (CD3hiCD4hi), model percent correct was 78%, p <0,05. The discriminant function was either f1 for distinguishing HVs versus ill patients SLE and pSS (all participants are accounted) or f2 for SLE versus pSS (only participants with disease are accounted). During ROC analysis, performed for the differential diagnosis of healthy and sick patients, this discriminant model had a sensitivity of 86,5% and a specificity of 72,8%, the area under the curve (AUC) 0.94, p <0.001. Among the group of ill patients, the differential diagnosis between SLE and pSS had a sensitivity of 69,6% and specificity of 64,8%, AUC 0.87, p <0.001. Graphic representation of the discriminant analysis is performed on Figure 1. The group of patients, meeting the criteria for both pSS and SLE, is between the main groups.Figure 1.Graphic distribution of SLE, pSS and pSS+SLE patients, as well as HVs analyzed by discriminant analysis.ConclusionT- and B-cell peripheral blood subsets might provide an additional diagnostic tool for distinction SLE, pSS and HVs. Differential diagnosis between pSS and SLE is difficult, because this diseases may coexist.References[1]Guillermo Carvajal Alegria, Pierre Gazeau1, Sophie Hillion et al. Could Lymphocyte Profiling be Useful to Diagnose Systemic Autoimmune Diseases? Clinic Rev Allerg Immunol (2017) 53:219–236[2]Sandra Gofinet Pasoto, Victor Adriano de Oliveira Martins, Eloisa Bonfa. Sjögren’s syndrome and systemic lupus erythematosus: links and risks. Open Access Rheumatol. 2019; 11: 33–45.Disclosure of InterestsNone declared
Adult-onset Still’s disease (AOSD) is a rare complex autoinflammatory disease of unknown etiology. The main problem, practitioners have been facing with when researching AOSD, is the lack of developed approaches to assessing the activity of the disease. Traditionally used standard markers of inflammation do not always reflect the real activity of AOSD, especially when a patient is already receiving anti-inflammatory therapy. The article presents original data on the study of biomarkers: interleukin-1 beta (IL-1b), interleukin-6 (IL-6), interleukin-18 (IL-18), ferritin, glycosylated ferritin, calprotectin, procalcitonin compared with C-reactive protein, leukocyte and neutrophil counts in patients with moderate and high activity of AOSD. The relationship between inflammatory biomarkers and the Pouchot systemic score was evaluated to identify promising laboratory indicators of disease activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.