Vaccination against respiratory tract pathogens in primary immune deficiency patients receiving immunoglobulin replacement therapy.

Introduction: Inborn errors of immunity (IEI) increase morbidity and mortality risks, particularly from respiratory tract infections. Hence, vaccination becomes pivotal for IEI patients. This study aims to examine the vaccination and respiratory tract infection rates in a diverse IEI patient cohort undergoing immunoglobulin replacement therapy (IGRT). Materials and Methods: We retrospectively evaluated IEI patients on IGRT at a tertiary care center. Data on vaccinations and respiratory infections were extracted from medical records. Result: : The study included 33 patients (mean age= 37.7 ± 11.4 years; 17 male). The most common clinical phenotype in our cohort was primary antibody deficiencies (90.9%). Only two patients had a genetic diagnosis, both of whom were brothers diagnosed with Wiskott-Aldrich syndrome (WAS). Almost half (48.5%) of our patients had bronchiectasis and 81.8% were on prophylactic antibiotics. All patients with IEI included in the study were regularly receiving IGRT. The vaccination rate of patients against respiratory tract infections was 42.4%, 57.6%, and 78.8% for influenza, pneumococcus, and COVID-19, respectively. Only one patient (7.1%) who received the influenza vaccine developed an upper respiratory tract infection. However, viral panel analysis could not be performed for this patient as they did not present to the hospital. The COVID-19 vaccination rate was notably higher than that of other vaccines, likely due to increased awareness during the pandemic, aided by public advisories and media influence. Conclusions: We observed higher vaccination rates for the COVID-19 vaccine compared to other vaccines (influenza and pneumococcal vaccines). Although we observed the potential impact of social and governmental influence in increasing vaccination rates, it is crucial to acknowledge that vaccination decisions in IEI patients must be individualized.

The role of vitamin D receptor gene polymorphisms in the pathogenesis of Behçet's disease: A case-control study in Turkish population.

BACKGROUND: Behçet's disease (BD) is an inflammatory disorder characterized by oral aphthous lesions, uveitis, and genital ulcerations. The vitamin D receptor (VDR) has a crucial role in the pathogenesis of this disease because it mediates the functions of vitamin D in the immune system. Alterations of VDR expression related to polymorphic alleles of the VDR gene may play a pathogenic role in BD and BD's clinical presentations. METHODS: 150 BD patients and 150 healthy controls were included and genotyping was carried out by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: Significant differences between patients and controls in rs1544410, rs2228570, and rs731236 genotypes were observed (respectively, p = 0.04, p = 0.007, p = 0.012). The clinical characteristics of BD patients were evaluated and patients with ocular lesions had a higher percentage of rs1544410 A alleles (p = 0.004), and patients with oral aphthous lesions, a positive pathergy tests, and arthritis had more rs2228570 C alleles than patients without these clinical findings (respectively, p < 0.001, p = 0.021, p = 0.045). CONCLUSION: VDR gene polymorphisms may possibly have a role in the pathogenesis of BD through their effects on VDR expression and may be associated with the increased risk of several clinical findings.

The relationship of serum vitamin D receptor levels with disease activity and clinical parameters in patients with ankylosing spondylitis.

OBJECTIVES: The aim of this study was to investigate the relationship between serum vitamin D receptor (SVDR) levels and disease activity parameters in patients with ankylosing spondylitis (AS). PATIENTS AND METHODS: Between July 2016 and January 2017, a total of 62 patients (51 males, 11 females; mean age 36.5±12.8 years; range, 23 to 49 years) with AS and 32 healthy volunteers (25 males, 7 females; mean age 41.57±13.6 years; range, 26 to 48 years) were included in the study. The SVDR levels were measured using the enzyme-linked immunosorbent assay. Erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) levels were recorded. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were used to assess disease activity. RESULTS: Although there was no significant difference between the patient and control groups (p=0.66), SVDR levels were significantly elevated in patients with active AS (BASDAI score ≥4) (p=0.01). The SVDR levels significantly increased in AS patients with peripheral joint involvement and enthesitis (p=0.01, p=0.05, respectively). The SVDR levels significantly elevated in patients treated with non-steroidal anti- inflammatory drugs, compared to those treated with biological agents and control group (p=0.01, p=0.03, respectively). The SVDR levels were positively correlated with the BASDAI, CRP and ESR in the patient group (p=0.01, r=0.751; p=0.01, r=0.75; p=0.01, r=0.81, respectively). CONCLUSION: Our study results suggest that serum SVDR levels are associated with the disease activity and clinical parameters in patients with AS. Based on these findings, SVDR level may be used as a marker of disease activity in AS.

The importance of serum interleukin-20 levels in patients with Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a complex multisystemic disease with an unknown origin, which presents with aphthous and genital ulcers, cutaneous lesions, arthritis, ocular lesions, and defects in the gastrointestinal and central nervous systems. OBJECTIVES: In this study, we examined the relationship between serum interleukin-20 (IL-20) levels and disease activity in BD patients. MATERIAL AND METHODS: A total of 45 BD patients diagnosed according to the BD diagnosis criteria determined by the International Study Group for Behçet's Disease were included in the study. Out of 45 patients, 17 had inactive BD and 28 had active BD. The control group consisted of 25 healthy subjects. The IL-20 levels of all the groups were detected and compared with each other. Serum IL-20, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were examined. RESULTS: The IL-20 levels of the active BD patient group were significantly higher than in the control group (p < 0.001) and in the inactive BD patient group (p < 0.001). No statistically significant difference was detected between the IL-20 levels of the control group and the inactive BD patient group (p = 0.2). CONCLUSIONS: Higher IL-20 levels in active BD patients, when compared to inactive BD patients and healthy controls indicate that the disease is an inflammatory one and IL-20 plays a role in the disease pathogenesis. Moreover, it can be concluded that IL-20 might have a role in the complex process of the settlement and activation of the disease.

Investigating the role of IL-33 in the pathogenesis of Behçet's Disease.

OBJECTIVES: Behçet's disease (BD) is an inflammatory disease, characterized by oral aphthous lesions, recurrent uveitis, skin lesions, and genital ulcerations. Increased release of several cytokines may play a role in the inflammatory stages of BD. IL-33, a member of the IL-1 cytokine superfamily, plays an important role in inflammation. We analyzed serum IL-33 concentration in BD patients to assess its possible role in the pathophysiology of this disease. METHODS: The study included 54 BD patients, 31 with active BD and 23 with inactive BD as well as 18 matched healthy controls. Serum IL-33 levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean serum IL-33 levels were 4.84 ± 2.81 pg/ml in the BD patients (6.16 ± 2.94 pg/ml in the active stage and 2.86 ± 0.54 pg/ml in the inactive stage) and 2.88 ± 0.42 pg/ml in the healthy controls. Serum IL-33 levels were significantly higher in patients with BD compared with the healthy controls (p < 0.01). In active Behçet patients with arthritis the mean serum IL-33 level was higher but this finding was not statistically significant (p = 0.122). CONCLUSION: IL-33 may play a significant role of in the pathogenesis of BD.

Effect of Long-Term TNF-α Inhibition with Infliximab on Left Ventricular Torsion in Patients with Rheumatoid Arthritis.

INTRODUCTION: We evaluated the impact of tumor necrosis factor alpha (TNF-α) inhibition on left ventricular torsion (LVtor) in patients with rheumatoid arthritis (RA) using speckle-tracking echocardiography (STE). METHODS: Thirty-eight RA patients without cardiovascular disease and 30 healthy subjects were enrolled in the study. Twenty patients received infliximab, a monoclonal antibody against TNF-α, and 18 patients received increasing doses of prednisolone for 180 days. Global systolic longitudinal strain (G-LS), global systolic radial strain (G-RS) and global systolic circumferential strain (G-CS) were determined by STE. LV basal and apical rotations from the base and apex were obtained and used for calculation of LVtor. Pre-treatment LVtor levels were compared with LVtor levels after therapy in both treatment groups. RESULTS: RA patients had lower G-LS (-16.5 ± 2.9; p<0.01), G-RS (37.6 ± 1.5; p<0.01) and higher GCS (-23.6 ± 3.5; p=0.04) compared with control subjects (-20.0 ± 2.8, 40.7 ± 4.8, -22.4 ± 2.5, respectively; p<0.01). LVtor levels were significantly higher in RA patients compared to controls (16.4 ± 2.7 vs. 15.1 ± 2.5; p=0.04), which might be attributed to higher values of apical rotation (9.7 ± 2.4 vs. 8.8 ± 2.3; p=0.01). Patients treated with infliximab experienced a significant decrease in LVtor (p=0.04), and a significant increase in G-LS (p<0.01) and G-RS (p<0.01). No significant changes were observed among patients treated with prednisolone. Percentage changes in LVtor were correlated with percent changes in C-reactive protein CRP (r=0.58; p<0.01), disease activity score (r=0.78; p<0.01), and G-LS (r=-0.40; p=0.04) in patients treated with infliximab. CONCLUSIONS: RA is characterized by increased LVtor. Long term TNF-α inhibition improves LV longitudinal and radial systolic deformation and decreases LVtor.

Chronic inhibition of tumor necrosis factor-α with infliximab improves myocardial deformation in parallel with aortic elasticity in rheumatoid arthritis.

OBJECTIVES: This study investigated the effects of infliximab, a monoclonal antibody against TNFα, on myocardial deformation and aortic elasticity in patients with rheumatoid arthritis (RA), and the association of aortic elasticity with myocardial deformation. STUDY DESIGN: 38 female rheumatoid arthritis (RA) patients and 30 healthy controls were included in the study. Twenty patients received infliximab and 18 patients received prednisolone. Left ventricular (LV) longitudinal, circumferential and radial strain, systolic strain rate and early diastolic strain rate using speckle-tracking echocardiography, and aortic elasticity using M-mode echocardiography were assessed at baseline and post-treatment. RESULTS: LV systolic longitudinal basal-, mid-, and apical strain, systolic mid- and apical strain rate, basal-, mid- and apical early strain rate, circumferential systolic apical strain and systolic strain rate were reduced in RA patients compared to controls. Compared to baseline, infliximab treatment increased aortic strain, aortic distensibility and decreased aortic ß index. No significant aortic elastic changes were observed with prednisolone treatment. Longitudinal basal- and apical strain, basal-, mid- and apical systolic and diastolic strain rates, circumferential basal systolic strain, radial mid- and apical strain and apical strain rate were increased following infliximab treatment. Infliximab treatment improves aortic elasticity in parallel to myocardial deformation, but no significant association was observed following prednisolone treatment. CONCLUSION: Myocardial deformation is impaired in RA patients and is related to aortic stiffness. Chronic inhibition of TNFα improves LV deformation in association with aortic elasticity.

Infliximab, an anti-TNF-alpha agent, improves left atrial abnormalities in patients with rheumatoid arthritis: preliminary results.

BACKGROUND: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. In the current prospective study, we addressed the impact of RA on left atrial (LA) function and electrical remodelling. Further, we tried to demonstrate the effects of infliximab, an anti-TNF-alpha agent, on echocardiographical LA abnormality in RA patients with preserved left ventricular (LV) ejection fraction. METHODS: We compared 38 female RA patients without clinical evidence of heart disease and 30 female controls without RA and clinical evidence of heart disease. Further, we compared RA patients receiving infliximab and increasing doses of prednisolone over a three-month period. At baseline and post treatment, this study assessed (1) LA and LV parameters using conventional and speckle tracking echocardiography (STE), and (2) electrocardiographic P-wave changes. RESULTS: The values of C-reactive protein (CRP), isovolumic relaxation time (IVRT), A wave, and deceleration time (DT) were significantly higher in RA patients compared to the control group (p < 0.05), whereas E/E' and E/A values were found to be lower (p < 0.05) in RA patients. E/E' values were lower in prednisolone- compared to infliximab-treated patients (p < 0.05). After three months of infliximab and prednisolone treatment, CRP and disease activity score (DAS 28) values decreased in both groups (p < 0.05), and Duke activity status index (DASI) increased (p < 0.05). Maximal left atrial volume index (LAVImax), pre-contraction left atrial volume index (LAVIpreA) and maximum P wave (Pmax) of the RA patients were higher compared to the control group (p < 0.05), whereas LA global strain was found to be lower (p < 0.05). There was no difference in Pmax values between groups before and after the treatment period. E/E', LAVImax and LAVIpreA values of infliximab-treated patients decreased and LA global strain increased after three months of therapy compared to baseline (p < 0.05). At baseline in both treatment groups, E/E' and LA global late diastolic strain rate were lower in prednisolone-compared to infliximab-treated patients (p < 0.05). CONCLUSION: There was echocardiographic LA abnormality in these RA patients. In this patient group there was also a meaningful increase in maximum P wave assessed by electrocardiography. Infliximab therapy for a period of three months improved LA abnormality.

Impact of rheumatoid arthritis in Turkey: a questionnaire study.

OBJECTIVES: Unmet needs of rheumatoid arthritis (RA) patients regarding physician/patient communication, treatment preferences and quality of life issues were investigated in a Turkish survey study. METHODS: The study was conducted with the contribution of 33 rheumatologists, and included 519 RA patients. The study population included patients who had been on biologic therapy for >6 months and were still receiving biologic therapy (BT group), and those who were biologic naive, but found eligible for biologic treatment (NBT group). Of the RA patients, 35.5% initially had a visit to an internal disease specialist, 25.5% to a physical therapy and rehabilitation specialist, and 12.2% to a rheumatology specialist for their RA complaints. The diagnosis of RA was made by a rheumatologist in 48.2% of patients. RESULTS: The majority of RA patients (86.3%) visit their doctor within 15-week intervals. Most of the physician-patient communication focused on disease symptoms (99.0%) and impact of the disease on quality of life (61.8%). The proportion of RA patients who perceived their health status as good/very good/excellent was higher in the BT group than in the NBT group (74.3% vs. 51.5%, p<0.001). However, of those RA patients in the NBT group, only 24.8% have been recommended to start a biologic treatment by their doctors. With respect to dose frequency options, once-monthly injections were preferred (80%) to a bi-weekly injection schedule (8%). CONCLUSIONS: In conclusion, RA patients receiving biologic therapy reported higher rates of improved symptoms and better quality of life and seemed to be more satisfied with their treatment in our study.

The cost of care of rheumatoid arthritis and ankylosing spondylitis patients in tertiary care rheumatology units in Turkey.

OBJECTIVES: To determine the direct and indirect costs due to rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients in Turkey. METHODS: An expert panel was convened to estimate the direct and indirect costs of care of patients with RA and AS in Turkey. The panel was composed of 22 experts chosen from all national tertiary care rheumatology units (n=53). To calculate direct costs, the medical management of RA and AS patients was estimated using 'cost-of-illness' methodology. To measure indirect costs, the number of days of sick leave, the extent of disability, and the levels of early retirement and early death were also evaluated. Lost productivity costs were calculated using the 'human capital approach', based on the minimum wage. RESULTS: The total annual direct costs were 2,917.03 Euros per RA patient and 3,565.9 Euros for each AS patient. The direct costs were thus substantial, but the indirect costs were much higher because of extensive morbidity and mortality rates. The total annual indirect costs were 7,058.99 Euros per RA patient and 6,989.81 for each AS patient. Thus, the total cost for each RA patient was 9,976.01 Euros and that for an AS patient 10,555.72 Euros, in Turkey. CONCLUSIONS: From the societal perspective, both RA and AS have become burden in Turkey. The cost of lost productivity is higher than the medical cost. Another important conclusion is that indirect costs constitute 70% and 66% of total costs in patients with RA and AS, respectively.

Serum adiponectin levels in patients with familial Mediterranean fever.

Familial mediterranean fever (FMF) is a systemic disorder characterized by recurrent attacks of fever and polyserositis. In FMF, several pro-inflammatory cytokines have been found to be elevated during the attacks. In recent years, it is shown that some proteins originated from adipose tissue play important role in inflammatory process. One of them, adiponectin decreases the expression of adhesion molecules and inhibits the attachment of active macrophages to the endothelial surface, so that it acts antiinflammatory effect. In this study, we analyzed the possible role of serum adiponectin in the pathogenesis of FMF. Thirty five patients with FMF and 13 healthy controls (5 female,8 male; mean age 22.3 ± 4.2 years) were enrolled in this study. Fifteen patients were in active stage (6 female, 9 male, mean age; 22.4 ± 4.1 years, mean disease duration 6.1±2.3 years) and 20 patients were in inactive stage (6 female,14 male, mean age;22.6 ±4.2 years, mean disease duration; 5.7 ± 1.6 years). Serum adiponectin and IL-6 levels were determined by ELISA. The mean serum adiponectin levels were 5.3 ±1.6 ng/ml in healthy controls, 55.3 ± 21.8 ng/ml in active FMF patients and 17.1 ± 4.7 ng/ml in inactive FMF patients. The mean serum IL-6 levels were 1.9 ± 0.4 ng/ml in healthy controls, 4.7 ± 1.1 ng/ml in active FMF patients and 2.9 ± 1.3 ng/ml in inactive FMF patients. Serum adiponectin levels in patients with FMF were significantly higher than in healthy controls (p<0.001). Serum adiponectin levels were significantly high both in active FMF patients and in inactive FMF patients compared with healthy control (p<0.001, p<0.001 respectively). Serum IL-6 levels were significantly higher both in patients with active and inactive disease as compared with healthy controls (p<0.01 and p<0.05 respectively). In serum adiponectin levels were correlated with high levels of serum IL-6 in the active and inactive patients. Serum adiponectin and IL-6 levels were during both active and inactive stages in patents with FMF.

Plasma ghrelin levels in patients with Familial Mediterranean Fever.

Familial mediterranean fever (FMF) is a familial disease characterized by recurrent episodes of febrile serositis, peritonitis, arthritis and pleuritis. Many studies have been performed is an attempt to understand the basis of the inflammatory attacts in FMF. Ghrelin, a recently described orexigene peptide is predominantly produced by stomach. Ghrelin also exerts multiple regulatory effects on immune system. It has reported that grelin has anti-inflammatory effects. There is currently no published evidence demonstrating a role for anti-inflammatory effects of ghrelin in FMF. For this reason, we investigated the role of plasma ghrelin levels in patients with FMF. Thirty seven patients with FMF and 10 healthy controls (5 female, 5 male; mean age 35.4 +/- 5.6 years) were enrolled in this study. Twenty-one patients were in active stage (10 female, 11 male, mean age; 31.0 +/- 5.4 years, mean disease duration 7.2 +/- 3.3 years) and 16 patients were in inactive stage (7 female,9 male, mean age; 33.0 +/- 6.0 years, mean disease duration; 8.7 +/- 3.2 years). Plasma ghrelin levels were determined by EIA. The mean plasma ghrelin levels were 158.4 +/- 52.9 pg/ml in patients with FMF and 56.7 +/- 7.5 pg/ml in healthy controls. The mean plasma ghrelin levels were 190.5 +/- 49.4 pg/ml in the active patients and 116.2 +/- 11.7 pg/ml in the inactive patients. Plasma ghrelin levels were significantly high in patients with FMF compared to healthy controls (p<0.001). Plasma ghrelin levels were significantly high in the active patients compared to in the inactive patients and healthy controls (p<0.001 and p<0.001 respectively). There was significantly difference between in active and inactive patients with FMF (p<0.001). As a results; Plasma ghrelin levels were high both in active and inactive patients with FMF. It is showed that ghrelin may play significant role of the pathogenesis of FMF.

Diagnostic utility of anti-cyclic citrullinated peptide and anti-modified citrullinated vimentin antibodies in rheumatoid arthritis.

Several autoantibodies found in RA are directed to epitopes in citrullinated proteins. One of them is anti modified citrullinated vimentin (Anti-MCV). We tested the value a newly developed ELISA for the detection of antibodies against a genetically modified citrullinated vimentin (anti-MCV) in comparison with an anti-CCP based ELISA system for the diagnosis of RA. Thirty-five patients with RA (mean age; 42.6 +/- 10.87 years, mean disease duration; 9.37 +/- 3.98 years) were enrolled in this study. Twenty -five ankylosing spondylitis (mean age; 35.88 +/- 6.64 years, mean disease duration; 10.25 +/- 4.61 years), and 19 healthy subjects (mean age; 40.26 +/- 5.11 years) served as controls. Anti-CCP antibodies and Anti-MCV antibodies were measured using ELISA. In all RA patients, mean anti- CCP level was 69.07 +/- 90.43 U/ml and anti-MCV level was 665.77 +/- 1040.19 U/ml. In patients with AS, the mean anti-CCP level was 10.7 +/- 5.22 U/ml and anti-MCV level was 40.54 +/- 20.15 U/ml. In healthy controls, the mean anti-CCP level was 11.11 +/- 7.65 U/ml, anti-MCV level was 23.12 +/- 12.04 U/ml. In patients with active RA, the mean serum anti-CCP level was 100.54 +/- 98.07 U/ml and anti-MCV level was 998.74 +/- 1154.93 U/ml. In patients with inactive RA, the mean serum anti-CCP level was 8.77 +/- 1.55 U/ml and anti-MCV level was 27.59 +/- 23.10 U/ml. According to these results; In patients with RA, the mean serum anti-MCV and anti-CCP levels were significantly high compared to patients with AS and healthy controls (p=0.002, p=0.001, p=0.002, p=0.001 respectively). The mean serum anti-MCV and anti- CCP levels were significantly higher in active patients with RA than in inactive patients with RA patients (p=0.001 and p=0.001 respectively). In inactive patients with RA, the mean serum anti-MCV and anti-CCP levels were similar in patients with AS and patients (p=0.484, p=0.308, p=0.09 and p=0.222 respectively). The mean serum anti-MCV levels were correlated with DAS 28 (r=0.531, p=0.001), VAS score (r=0.332, p=0.01), ESR (r=0.458, p=0.001), serum CRP levels (r=0.568, p=0.01), serum RF levels (r=0.529, p=0.001), swollen joints number (r=0.525, p=0.001) and tender joints number (r=0.638, p=0.001). As a result; measurement of serum anti-MCV levels is useful for diagnosis of RA and combined use of anti-MCV and RF may be more useful prognostic factor than either method alone, RF and anti-CCP.

In vitro nonspecific mitogenic response of T-cell subsets in acute and chronic brucellosis.

The aim of the present study was to determine the cellular immune response on the course of brucellosis by investigating the proliferation response of T-cell subsets to phytohemagglutinin (PHA), that is, nonspecific mitogen in the patients with acute and chronic brucellosis. The study was performed in 19 patients with untreated brucellosis (acute, n = 11; chronic, n = 8) and 19 healthy controls. Standard tube agglutination and Coombs tests for brucellosis were performed. CD4+ and CD8+ T cell were investigated by the flow cytometry and sorting methods in all of cases. After these cells were cultured and stimulated with PHA, [H3]-thymidine uptake and stimulation indices (SIs) were established. In all of the patients with brucellosis, CD4+ SIs and CD8+ SIs were found to be 1.40 +/- 0.63 and 1.45 +/- 0.42, respectively, and in the controls CD4+ SIs and CD8+ SIs were 1.59 +/- 0.36 and 1.64 +/- 0.37, respectively. In acute cases, CD4+ SIs were 1.71 +/- 0.64 and CD8+ SIs were 1.54 +/- 0.45. CD4+ SIs were 0.97 +/- 0.25 and CD8+ SIs were 1.32 +/- 0.37 in chronic cases. Although in acute cases CD4+ SIs and CD8+ SIs were not different from those in the control group, CD4+ SIs of chronic brucellosis cases were found to be significantly low as compared with those of acute brucellosis cases and the controls (P < 0.01). CD8+ SIs of acute and chronic brucellosis cases were not found to be different from those in the controls. Brucella agglutination titers of the patients with acute and chronic brucellosis were not found related with CD4 SIs and CD8 SIs. The findings of significantly low results of CD4+ T-cell proliferative responses of chronic brucellosis to PHA as compared with control and acute brucellosis cases remind that the development of chronic infection might be a result of T-helper proliferation defect.