Nihal Mete Gökmen

Cigarette smoking in primary Sjögren’s syndrome: positive association only with ANA positivity

Smoking is well known to contribute to the pathogenesis and severity of some systemic autoimmune rheumatic diseases and especially to the production of certain autoantibodies. Primary Sjögren’s syndrome (pSS) is an autoimmune disease, affecting primarily the exocrine glands. It may also cause extraglandular involvement in some cases. In this study, we aimed to determine the frequency of smoking habits in our cohort of pSS patients and to investigate whether the frequencies of autoantibody positivity and extraglandular involvement were significantly different between patients with and without smoking. In this cross-sectional study, 207 patients with pSS (F/M 203/4), fulfilling the United States-European Consensus Criteria, and 602 healthy controls (F/M 534/68) were included. Patients and controls were classified into five groups: never smokers, current smokers, former smokers; ever smokers, and passive smokers. The χ2 and Kruskal–Wallis tests were used for statistical analysis; a p value of less than 0.05 was accepted as statistically significant. While the frequency of current smokers was significantly lower in the pSS group compared with the healthy controls (11.6 vs 22.3%), the frequencies of former smokers (30.4 vs 11.8%), ever smokers (42.0 vs 34.1%), and passive smokers (47.3 vs 37.5%) were significantly higher in the pSS group compared with the healthy controls. In pSS patients, only antinuclear antibody (ANA) positivity was significantly associated with smoking habits, while there was no significant association with other autoantibodies or with the presence of extraglandular involvement. We found that in pSS patients smoking was significantly associated only with ANA positivity. Unlike the deleterious effects of smoking upon disease severity and anti-cyclic citrullinated protein (CCP) antibody production in rheumatoid arthritis, we could not find any association of smoking with extraglandular involvement and/or anti-Ro/anti-La antibody positivity in pSS. These results are indeed in line with the limited number of previous studies reported in the literature. Further studies with higher numbers of pSS patients are required to confirm the seemingly negative association of smoking with pSS.

Desensitization Effect of Preseasonal Seven-Injection Allergoid Immunotherapy with Olive Pollen on Basophil Activation: The Efficacy of Olive Pollen-Specific Preseasonal Allergoid Immunotherapy on Basophils

Background: It has previously been demonstrated that subcutaneous immunotherapy with allergoids positively affects clinical and immunological parameters even after 7 preseasonal injections. However, its effect on basophil activation remains unclear. We investigated the effect of preseasonal allergoid immunotherapy on basophils and concomitantly assessed its clinical and immunological efficacy in olive pollen-monosensitized patients. Methods: This study enrolled 437 consecutive patients with respiratory allergy and positive skin prick tests (SPTs); 212 (48.5%) patients were sensitized to olive pollen, and 33 (7.5%) patients were sensitized to olive pollen only. Of these patients, 23 received preseasonal immunotherapy with an olive pollen allergoid. The olive pollen-specific basophil activation, the titrated nasal provocation test, the nasal symptom score, and olive pollen-specific IgE, IgG1 and IgG4 levels were evaluated before immunotherapy and 8 months after the end of immunotherapy in the follow-up visit. Results: In comparison to baseline evaluation, 7 preseasonal injections of an allergoid resulted in a significant decrease in the percentage of basophils expressing CD63 (29 vs. 7%, respectively, p < 0.0001) and a significant increase in the titrated nasal provocative dose (1/10 vs. 1/1, respectively, p < 0.01). SPT induration diameters caused by an olive pollen extract decreased (12 mm at baseline vs. 5.5 mm at follow-up, p < 0.005), as did nasal symptom score (7 at baseline vs. 3 at follow-up, p < 0.01). Olive pollen-specific IgE (17.5 vs. 50 kU/l, p < 0.012), IgG1 (0.16 vs. 2.9 µg/ml, p < 0.0001) and IgG4 (0.07 vs. 1.92 µg/ml, p < 0.0001) levels significantly increased. Conclusions: Immunotherapy with 7 preseasonal injections of an olive pollen allergoid decreases olive pollen-specific basophil activation over 8 months, an effect observed in vitro and in vivo.

Phagocytic and oxidative burst activity of neutrophils in patients with spinal cord injury.

OBJECTIVE To evaluate phagocytic activity and neutrophil oxidative burst functions in patients with spinal cord injury (SCI) because alterations in neutrophil metabolic activity can be one of the causes of immune mechanism damage contributing to repeated bacterial infections. DESIGN A controlled and cross-sectional study. SETTING Departments of physical medicine and rehabilitation and immunology. PARTICIPANTS Patients with SCI (N=34) and 28 healthy controls. INTERVENTIONS Phagocytosis and oxidative burst in whole-blood neutrophils were assessed by flow cytometry. The percentage of phagocytizing cells after in vitro incubation with Escherichia coli, phagocytic activity (mean intensity of fluorescence [MIF]) and the percentage of neutrophiloxidative burst, and the MIF value of the production of reactive oxygen intermediates (ROIs) were analyzed. In addition, clinical assessment including the level of injury, American Spinal Injury Association scores, and functional status were carried out. MAIN OUTCOME MEASURES Not applicable. RESULTS Although the percentage of E. coli phagocytizing neutrophils was not different between groups, the MIF value of absorbed E. coli was significantly lower in patients with SCI than in controls (P<.05). The MIF value of ROI production by neutrophils with both stimulator of phorbol 12-myristate 13-acetate and E. coli was significantly higher in patients with SCI (P<.05). CONCLUSIONS In patients with SCI, decreased phagocytic activity of neutrophils may be a result of a regulatory mechanism to minimize the deleterious effects of increased neutrophil burst activity.

The Turkish Hereditary Angioedema Pilot Study (TURHAPS): The First Turkish Series of Hereditary Angioedema

Background: No published data presently exist concerning hereditary angioedema (HAE) in Turkey. The aim of the study was to initiate a preliminary multicentric evaluation about HAE and to determine the genetic properties of Turkish patients. Methods: Based on records drawn from four medical centers we identified a total of 70 subjects, belonging to 60 unrelated families, fulfilling clinical and laboratory criteria for diagnosis of HAE with C1 inhibitor deficiency. Ten type I patients, and their first-degree relatives, underwent genetic analysis for HAE. Results: The majority of patients were female (60%), the mean age was 37.7 ± 14.1 years. The mean age at the time of first angioedema symptom was 12.5 ± 9.2 years. Mean time lag between first symptom and diagnosis was 26 ± 14.4 years. All but 3 subjects had HAE type I. Family history of angioedema was present in 75.7% of the cases. Cutaneous swelling was reported by 87.1% of the patients, facial edema by 65%, abdominal symptoms by 74.3% and approximately one half (55.7%) had experienced one or more laryngeal attack. Genetic analysis of 10 families demonstrated that 5 carried a mutation that had never been previously described. Conclusion: We found that the clinical features of Turkish HAE patients were consistent with previously described patterns of this rare disease. The most noteworthy feature identified in the study was a significantly long duration between the first symptom appearance and final diagnosis. Our detection of different mutations in 10 patients confirms the allelic heterogeneity of the disease.

Risk factors for a poor hematopoietic stem cell mobilization

Poor mobilization is an important problem in autologous stem cell transplantation. We retrospectively reviewed the data of 165 mobilized patients to identify possible risk factors for a poor stem cell mobilization. 27 patients (16.4%) were categorized as poorly mobilized. The poor mobilization ratio differed according to diagnosis (lymphoma: 25.4%, acute leukemia: 15.4%, amyloidosis: 14.3%, and multiple myeloma: 9.6%). Being diagnosed as lymphoma (odds ratio [OR]=6.02, p=0.001), advanced age (OR=1.05, p=0.007) and increased weight (OR=1.03, p=0.03) were found as possible risk factors. Being diagnosed as lymphoma was shown to be the most important risk factor for a poor mobilization. Leukapheresis staff should be aware of the increased risk of a poor mobilization in lymphoma patients and remobilization methods should be considered from the beginning.

Necrotizing Fasciitis in Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, progressive, and life-threatening hematopoietic stem cell disorder characterized by complement-mediated intravascular hemolysis and a prothrombotic state. Patients with PNH might have slightly increased risk of infections due to complement-associated defects subsequent to CD59 deficiency. Here, we report a rare case of a 65-year-old male patient with necrotic ulcers on both legs, where the recognition of pancytopenia and microthrombi led to the diagnosis of PNH based on FLAER (FLuorescent AERolysin) flow cytometric analysis. He was subsequently started on eculizumab therapy, with starting and maintenance doses set as per drug labelling. Progression of the patients leg ulcers during follow-up, with fulminant tissue destruction, purulent discharge, and necrotic patches, led to a later diagnosis of necrotizing fasciitis due to Pseudomonas aeruginosa and Klebsiella pneumonia infection. Courses of broad-spectrum antibiotics, surgical debridement, and superficial skin grafting were applied with successful effect during ongoing eculizumab therapy. This case highlights the point that it is important to maintain treatment of underlying disorders such as PNH in the presence of life-threatening infections like NF.

The difference in lactate dehydrogenase activity between pre- and post-mobilization periods is a good indicator of successful stem cell mobilization.

Predicting poor stem cell mobilization may prevent the costs and complications associated with remobilization. We retrospectively reviewed the relationship between serum lactate dehydrogenase (sLDH) activity and peripheral blood CD34 (PBCD34) cell counts in 46 granulocyte colony stimulating factor (G-CSF) induced mobilization cycles with or without chemotherapy. A significant correlation between post-mobilization (pre-apheresis) sLDH activity and PBCD34 count was found (r(s)=0.43, p=0.007). A strong correlation was shown between the pre- and post-mobilization sLDH activity difference and PBCD34 count (r(s)=0.55, p=0.001). With respect to sLDH activity differences; (a) all patients with a difference of >300 U/L, (b) 71% of patients with a difference of 100-300 U/L, and (c) 44% of patients with a difference of <100 U/L were considered to have good mobilizations. The sLDH activity difference between pre- and post-mobilization is a good indicator of successful mobilization. According to our results, the success of mobilization can be predicted based on sLDH activity differences; (i) good mobilization if the difference is >300 U/L, (ii) intermediate risk if the difference is 100-300U/L, and (iii) high risk if the difference is <100 U/L.

CD31 expression on peripheral blood stem cells predicts both early neutrophil and platelet engraftments

No detailed information currently exists about the immune phenotypic profiles of peripheral blood stem cells (PBSCs) obtained by different mobilization regimens. The effects of these profiles on the outcome of transplantation are largely unknown. In this prospective study, the surface immune phenotypic features (CD11a, CD18, CD31, CD38, CD44, CD62e, CD62L, CD90, CD117, CD135 and CD184 expression) of sorted PBSCs that had been mobilized by growth factor with (group I and group II) or without (group III) disease-specific chemotherapies were investigated. The immune phenotypic features on mobilized PBSCs in groups I, II and III were not significantly different. The CD31 (platelet endothelial cell adhesion molecule-1) positivity ratio on PBSCs inversely correlated with both the duration of neutrophil (r=-0.32, p=0.03) and platelet (r=-0.36, p=0.02) engraftment. No relationship was found between the engraftment (neutrophil and platelet) durations and CD184 (chemokine receptor CXC motif receptor 4 [CXCR4]) expression on PBSCs. We demonstrated that the surface immune phenotypic profiles on PBSCs obtained by several mobilization regimens were not different. To our knowledge, this is the first study to demonstrate that CD31 expression on human PBSCs may positively affect both neutrophil and platelet engraftment. Contrary to our expectations, CD184 (CXCR4) expression on PBSCs has no effect on neutrophil or platelet engraftment. Considered together, our results suggest that additional surface antigens (such as CD31) may be more effective in the homing process.

Misleading Allergens in the Diagnosis of Latex Allergy: Profilin and Cross-Reactive Carbohydrate Determinants

Background: It has been suggested that latex-specific IgE analysis may lead to false-positive results, especially in patients with pollen allergy. In the present study, the reasons underlying clinically irrelevant latex-specific IgE positivity were investigated. Methods: Thirty patients with latex allergy (group 1), 89 patients sensitised to aeroallergens (group 2a), and 98 healthy individuals without allergy (group 2b) were enrolled. Participants from all 3 groups were subjected to skin prick tests with aeroallergens including latex, latex-specific IgE analysis (ImmunoCAP), and nasal provocation test with latex. All cases demonstrating positive latex-specific IgE also underwent specific IgE tests (ImmunoCAP) with latex profilin, birch pollen profilin, peach lipid transfer protein, and pineapple bromelain as cross-reactive carbohydrate determinants. Results: Comparison of the atopic and healthy control groups showed that the rate of positive latex-specific IgE was significantly higher in group 2a. Latex profilin-, birch pollen profilin-, and bromelain-specific IgE were remarkably higher in group 2a. Conclusion: False positivity to latex-specific IgE in ImmunoCAP analysis may be observed in approximately 19% of patients with pollen allergy. Profilins and bromelain are the main contributors to clinically irrelevant positive latex-specific IgE.

Deletions in SERPING1 Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity

Background: How genotype affects phenotype in hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) has not been totally clarified. In this study, we investigated the relationship between different types of mutations and various phenotypic characteristics. Methods: Clinical data from 81 patients from 47 families were recorded. Complement proteins were analyzed from 61 untreated patients. The coding exons and the exon-intron boundaries of the SERPING1 gene were sequenced, and deletion/duplication analysis with multiple ligation dependent probe amplification was performed. The relationship of complement protein with the mutation type was analyzed by using generalized estimating equations. Results: Thirty-five different mutations (15 novel and 2/15 homozygous) were identified. There was no causative mutation in 6 patients (7.4%). Patients with deletion and large deletion had the lowest (5.05%, 0–18.7; 5.8%, 0–16.5%, respectively), and the none mutation group had the highest C1 inhibitor function (23.3%, 11–78%, p < 0.001). C1 inhibitor function levels decreased as the age of the disease progressed (r = –0.352, p = 0.005). Lower C1 inhibitor function levels caused severer disease (r = –0.404, p = 0.001) and more frequent annual attacks (r = –0.289, p = 0.024). In the off-attack period, C1q levels were lower than normal in 9.8% of the patients. Conclusion: Deletion mutations may represent the most unfavorable effect on C1 inhibitor function. The earlier disease onset age could be a sign for lower C1 inhibitor function levels in adult life. C1q levels could also be low in C1-INH-HAE patients, as in acquired angioedema. Lower C1 inhibitor function can predict disease severity and may have negative impacts on the course of C1-INH-HAE.