Immunogenicity of Infliximab Among Patients With Behçet Syndrome: A Controlled Study.

Background: Immunogenicity of tumor necrosis factor alpha inhibitors (TNFis) has been recognized as an important problem that may cause loss of efficacy and adverse events such as infusion reactions. TNFis are being increasingly used among patients with Behçet syndrome (BS) and scarce data exist on this topic. Objective: We aimed to investigate the prevalence of anti-infliximab (IFX) antibodies in patients with Behçet syndrome together with suitable controls. Methods: We collected serum samples from 66 consecutive Behçet syndrome patients (51 M, 15 F, mean age 37 ± 9 years) who were treated with IFX. Additionally, similarly treated 27 rheumatoid arthritis, 53 ankylosing spondylitis, 25 Crohn's disease patients, and 31 healthy subjects were included as controls. Samples were collected just before an infusion, stored at -80°C until analysis, and serum IFX trough levels and anti-IFX antibodies were measured by ELISA. We used a cut-off value of 1 µg/ml for serum IFX trough level, extrapolating from rheumatoid arthritis studies. Results: Anti-IFX antibodies were detected in four (6%) Behçet syndrome, five (18.5%) rheumatoid arthritis, three (12%) Crohn's disease, and one (2%) ankylosing spondylitis patient. The median serum IFX trough level was significantly lower in patients with anti-IFX antibodies compared to those without antibodies [2.32 (IQR: 0.6-3.6) vs. 3.35 (IQR: 1.63-5.6); p = 0.019]. The serum IFX trough level was lower than the cut-off value in 6/13 (46%) patients with anti-IFX antibodies and in 25/158 (16%) patients without anti-IFX antibodies (p = 0.015). Among the four Behçet syndrome patients with anti-IFX antibodies, two experienced relapses and two had infusion reactions. Conclusions: Immunogenicity does not seem to be a frequent problem in Behçet syndrome patients treated with IFX, but may be associated with relapses and infusion reactions, when present.

Recurrent Sertoli-Leydig cell tumor of ovary in 8-year-old girl.

Sertoli-Leydig cell tumors are rare sex cord-stromal neoplasms that account for <0.2% of ovarian tumors. These tumors with a retiform pattern pose difficult diagnostic problems, with the majority of being misinterpreted as serous papillary cystadenocarcinoma and endodermal sinus tumor. We report an 8-year-old female patient presented to our institution with a huge mass and pain in the lower abdomen and recurrence in the 10th months following the first operation. Only four cases of Sertoli-Leydig cell tumors have been reported under age of the eight years in the literature so far. It is difficult to define the stage and the morphology of Sertoli-Leydig cell tumors with retiform pattern in children and chemotherapy or radiotherapy administration is contraversial. However, fertility sparing surgeries should be considered as a first treatment choice on the time of the diagnosis and the recurrence.

Antineutrophil cytoplasmic antibody frequency in chronic hepatitis B patients.

BACKGROUND: Chronic hepatitis B (CHB) is a viral disease, common across the world, and associated with several extraintestinal manifestations including vasculitis. Antineutrophil cytoplasmic antibodies (ANCAs) are sensitive and specific markers for vasculitides. There is limited data available in the literature on whether ANCA formation is stimulated by CHB infection. In the present study we aimed to identify the frequency of ANCA in CHB patients. METHODS: A total of 174 subjects were included in the study (87 CHB patients, 87 control subjects). Perinuclear-ANCA (P-ANCA), cytoplasmic-ANCA (C-ANCA), myeloperoxidase ANCA (MPO-ANCA), and proteinase 3-ANCA (PR3-ANCA) were studied. IFA was used for P-ANCA and C-ANCA assays, and ELISA was used for MPO-ANCA and PR3-ANCA assays. RESULTS: ANCA positivity was high in both groups (31% in the CHB group and 26% among controls). There were no significant differences between the groups for P-ANCA and MPO-ANCA (P = 0.6 and P = 0.6, resp.). Frequency of borderline positive C-ANCA and all positive PR3-ANCA (positive + borderline positive) was significantly higher in the CHB group (P = 0.009 and P = 0.005, resp.). CONCLUSIONS: In the present study, the frequency of ANCA was high in both groups. The CHB group had a relatively higher frequency of ANCA positivity compared to controls. Borderline positive C-ANCA and positive PR3-ANCA were significantly higher in the CHB group. These results suggest that ANCA may have a high prevalence in Turkey. Patients with CHB should be evaluated particularly for C-ANCA and PR3-ANCA in the presence of vasculitic complaints and lesions.

Quantiferon-TB Gold in tube assay for the screening of tuberculosis before and during treatment with tumor necrosis factor alpha antagonists.

INTRODUCTION: The usefulness of interferon-gamma (IFN-γ) release assays for tuberculosis screening before tumor necrosis factor-alpha (TNF-α) antagonists and for monitoring during treatment is a contraversial issue. The aims of this study were to determine whether TNF-α antagonists affect the results of the Quantiferon-TB Gold in-tube assay (QTF); to assess how QTF performs in comparison with the tuberculin skin test (TST) in rheumatoid arthritis (RA) patients who are about to start treatment with TNF-α antagonists, RA patients who are not candidates for treatment with TNF-α antagonists, rheumatology patients with confirmed current or past tuberculosis infection, and healthy controls, and to determine the specificity of the QTF test to differentiate leprosy patients, another group of patients infected with mycobacteria. METHODS: The 38 RA patients who were prescribed TNF-α antagonists, 40 RA patients who were not considered for TNF-α antagonist use, 30 rheumatology patients with a history or new diagnosis of tuberculosis, 23 leprosy patients, and 41 healthy controls were studied. QTF and TST were done on the same day, and both were repeated after a mean of 3.6 ± 0.2 months in patients who used TNF-α antagonists. RESULTS: Treatment with TNF-α antagonists did not cause a significant change in the QTF or TST positivity rate (34% versus 42%; P = 0.64; and 24% versus 37%; P = 0.22). Patients with leprosy had a trend for a higher mean IFN-γ level (7.3 ± 8.0) and QTF positivity (61%) than did the other groups; however, the difference was not significant (P = 0.09 and P = 0.43). CONCLUSIONS: Treatment with TNF-α antagonists does not seem to affect the QTF test to an appreciable degree. The higher IFN-γ levels in leprosy patients deserves further attention.

The effects of provocation by foods with raised IgG antibodies and additives on the course of Crohn's disease: a pilot study.

BACKGROUND/AIMS: This study was designed to assess the role of foods with raised IgG antibodies and additives on the symptoms and inflammation of Crohn's disease. METHODS: Eight patients with Crohn's disease in remission were studied. They followed a strict diet during phase I. Then, provocations with two, three-day periods (phases II and III) followed: in phase II, pure forms of foods with high IgG antibodies and in phase III, off-the-shelf forms of those foods were added. Stool samples were collected for fecal calprotectin assay. Blood samples were taken on the 11th and 17th days for highly sensitive C-reactive protein, ferritin, erythrocyte sedimentation rate, white blood cells, and platelets. Patients kept a diet-symptom diary. RESULTS: Increased Crohn's disease activity index scores were found statistically significant (p=0.012) between pre- and during the provocation weeks. There were significant increases according to Harvey-Bradshaw Index when the highest values during the phases I, II (p=0.027) and I, III (p=0.027) were compared. The increases in highly sensitive C-reactive protein (p=0.025) and white blood cells (p= 0.036) were found statistically significant. Fecal calprotectin levels showed day-to-day variability. When compared, the levels of fecal calprotectin increased in all patients on the last day of the restriction (10th day) and the first day of the provocation (11th day) with the exception of one patient. CONCLUSIONS: Foods with raised IgG antibody levels and food additives can provoke the symptoms and may stimulate the inflammation in patients with Crohn's disease. Addition of a proper diet with restriction of those foods may be beneficial in the medical treatment.

A comparison of antineutrophil cytoplasmic antibody prevalence in patients treated and untreated for hyperthyroidism.

We aimed to compare the prevalence of antineutrophil cytoplasmic antibody (ANCA) and its subgroups between on-treatment (with anti-thyroid drugs; propylthiouracil, methimazole) and untreated patients with hyperthyroidism in our unit. Overall 78 consecutive patients were enrolled in the study; 45 patients were on-treatment (female/male 31:14) and 33 were newly diagnosed (female/male 20:13). We have studied ANCA, perinuclear-ANCA (p-ANCA), cytoplasmic-ANCA (c-ANCA), myeloperoxidase-ANCA (mpo-ANCA), and proteinase 3-ANCA (pr3-ANCA) in sera of all the patients. The data about clinical status, laboratory tests, and physical examination and mean duration of treatment in treated group were recorded. There was no statistically significant difference between the two groups for ANCA, c-ANCA, and pr3-ANCA (P=0.13, P=0.07, and P=0.63 respectively). p-ANCA and mpo-ANCA prevalences were significantly higher in on-treatment group than in untreated group (P=0.04 and P=0.01, respectively). The mean duration of treatment was 17 months in on-treatment group. The use of antithyroid drugs (propylthiouracil, methimazole) seems to be correlated with increased prevalence of ANCA. These drugs may especially increase p-ANCA and mpo-ANCA positivity.

Intima-media thickening in patients with familial Mediterranean fever.

OBJECTIVE: The aim of this study was to assess the frequency of atherosclerotic plaques and intima-media thickness (IMT) in patients with FMF and suitable controls. METHODS: We studied 100 (46 males, 54 females; mean age: 40 +/- 6 years) patients with FMF. Also 94 (15 males, 79 females; mean age: 41 +/- 7 years) patients with SLE and 103 (44 males, 59 females; mean age: 40 +/- 5 years) apparently healthy volunteers were included as the control groups. Subclinical atherosclerosis was assessed by investigating atherosclerotic plaques and measuring IMT from carotid and common femoral arteries using B-mode ultrasonography (USG). Traditional atherosclerotic risk factors were also assessed. RESULTS: Both FMF and SLE patients had significantly higher carotid (C-IMT) and femoral artery IMT (F-IMT) compared with healthy controls. This was also true after adjustment for atherosclerotic risk factors. Only patients with SLE were found to have higher frequency of atherosclerotic plaques in the carotid and in the carotid and/or femoral artery. When all atherosclerotic risk factors were adjusted, again only patients with SLE were found to have risk for atherosclerotic plaques. In FMF, whereas the presence of atherosclerotic plaques was only associated significantly with diabetes mellitus; C-IMT was correlated with age, BMI and fasting glucose; and F-IMT with age and BMI. CONCLUSIONS: Increased atherosclerosis defined as the presence of plaques was not observed in patients with FMF. The significance of increased C- and F-IMT among patients with FMF must be further assessed.