Ali Inal

Study of Autoimmunity in Klinefelter's Syndrome and Idiopathic Hypogonadotropic Hypogonadism

Sex hormones play an important role in determining the progression and severity of autoimmune diseases, but the in vivo mechanisms underlying this relation are poorly understood. The main objective of current study has been to compare the changes in neuroendocrine immune features and autoantibody profile in male patients with hypogonadotropic and hypergonadotropic hypogonadism, and to determine the relationships between sex hormones and immunologic parameters. Thirty-seven male patients with Klinefelters syndrome and 35 men with idiopathic hypogonadotropic hypogonadism who had no history of previous hormonal therapy and 30 healthy men were recruited in the study. Serum autoantibody profile, sex hormones, and immunologic parameters were studied. In conclusion, our findings suggest that both humoral and cellular immunity is enhanced in male hypogonadism. Klinefelters syndrome patients also had increased frequency of antiextractable nuclear antibodies and anticardiolipin antibodies positivity compared to idiopathic hypogonadotropic hypogonadism patients. It is possible that testosterone deficiency and increased levels of estradiol are primary responsible factors for this enhanced autoantibody production in Klinefelters syndrome patients.

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.

Evidence of chronic Chlamydia pneumoniae infection in patients with Behçet's disease.

Behc¸ets disease is a chronic vasculitis of unknown aetiology. Particular viral and bacterial pathogens have long been suspected of playing a role in the pathogenesis of the disease. Chlamydia pneumoniae is an intracellular bacterium capable of causing chronic infections. Some reports have suggested that the microorganism might be involved in the pathogenesis of vasculitis. The purpose of the present study was to investigate a possible correlation between C. pneumoniae infection and Behc¸ets disease. For this purpose, 90 consecutive patients with Behc¸ets disease and 50 healthy controls were enrolled. Immunoglobulin A (IgA) and IgG antibodies to C. pneumoniae were determined by 2 different techniques, namely indirect fluorescent antibody assay (IFA) and enzyme linked immunosorbent assay (ELISA). IgA antibodies to C. pneumoniae were detected in 17 (18.9%) patients with Behc¸ets disease and in 1 (2%) healthy control by IFA. By ELISA 27 patients (30.0%) and 6 controls (12.0%) had C. pneumoniae IgA. A significant difference was observed for IgA seropositivity between the 2 groups. Although IgG seropositivity between the 2 groups did not differ significantly, the number of individuals with IgG titres of ≥1:1000 was significantly higher in the patient group (43.1%) compared with the control group (13.9%). These finding provide serological evidence of chronic C. pneumoniae infection in association with Behc¸ets disease.

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.

Anticardiolipin Antibodies in Children with Helicobacter pylori Infection.

Anticardiolipin (aCL) antibodies are associated with thrombosis and have an important role in the etiology of diseases such as stroke and myocardial infarction whose etiologies were based on thrombosis. H. pylori has been proposed to be responsible for the pathophysiology of some diseases including stroke, myocardial infarction, thrombosis, and autoimmune diseases. From this point of view, we hypothesized a possible relationship between H. pylori infection and aCL antibodies and initially aimed to determine the prevalence of aCL antibody positivity in children with H. pylori infection.

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.