Association of the angiotensinogen M235T and angiotensin-converting enzyme insertion/deletion gene polymorphisms in Turkish type 2 diabetic patients with and without nephropathy

OBJECTIVE: Recent studies have suggested an association between a deletion variant of the angiotensin-converting enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for the development and progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS: We investigated the relationship of the ACE insertion/deletion (I/D) and AGT M235T gene polymorphisms in Turkish patients with type 2 diabetes mellitus (DM) with and without diabetic nephropathy. A total of 102 individuals were screened for the presence of the ACE I/D and AGT M235T polymorphism: 46 individuals who had type 2 DM with diabetic nephropathy and, as controls, 56 individuals who had type 2 DM without diabetic nephropathy. Gene polymorphisms were determined by the specific melting temperature (T(m)) values of the resulting amplicons after real-time online polymerase chain reaction and melting curve analysis. RESULTS: The frequencies of the ACE DD, ID, and II genotypes were 34.8%, 37.0%, and 28.3%, respectively, among type 2 diabetic patients with nephropathy, and 33.9%, 42.9%, 23.2%, respectively (P=.788), in the control subjects without diabetic nephropathy. On the other hand, the frequencies of the AGT MM, MT, and TT genotypes among the same groups were 26.1%, 52.2%, 21.7% and 26.8%, 57.1%, 16.1%, respectively (P=.758). CONCLUSIONS: There were no differences in the frequencies of the AGT M235T and ACE I/D genotypes between Turkish patients with type 2 DM with and without nephropathy.     

The Prevalances and Patient Characteristics of Primary Immunodeficiency Diseases in Turkey—Two Centers Study

Purpose

Primary immunodeficiency diseases (PIDs) are inherited disorders of the immune system resulting in increased susceptibility to unusual infections and predisposition to autoimmunity and malignancies. The European Society for Immunodeficiencies (ESID) has developed an internet-based database for clinical and research data on patients with PID. This study aimed to provide a minimum estimate of the prevalence of each disorder and to determine the clinical characteristics and outcomes of patients with PID in Turkey.

Methods

Clinical features of 1435 patients with primary immunodeficiency disorders are registered in ESID Online Patient Registry by the Pediatric Immunology Departments of the Medical Faculties of Uludag University and Ege University Between 2004 and 2010. These two centers are the major contributors reporting PID patients to ESID database from Turkey.

Results

Predominantly antibody immunodeficiency (73.5 %) was the most common category followed by autoinflammatory disorders (13.3 %), other well defined immunodeficiencies (5.5 %), congenital defects of phagocyte number, function or both 3.5 %), combined T and B cell immunodeficiencies (2 %), defects in innate immunity (1 %), and diseases of immune dysregulation (0.7 %). Patients between 0 and 18 years of age constitued 94 % of total and the mean age was 9.2?±?6 years. The consanguinity rate within the registered patients was 14.3 % (188 of 1130 patients). The prevalance of all PID cases ascertained from the registry was 30.5/100.000. The major cause of the mortality was severe infection which was seen in forty-two of seventy five deceased patients. The highest mortality was observed in patients with severe combined immunodeficiencies and ataxia-telangiectasia.

Conclusion

Promoting the awareness of PID among the medical professionals and the general public is required if premature death and serious morbidity occurs due to late diagnosis of the wider spectrum of PID are to be avoided.     

Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries

Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rβ1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought.     

Decreased ratio of CD4/CD8 lymphocytes might be predictive for successful interferon alpha and lamivudine combined therapy in childhood chronic hepatitis B infection: A preliminary study

BACKGROUND: In the development of chronic hepatitis with hepatitis B virus infection and in response to therapy, the immune status of the infected host plays a critical role. In this study, immunological variables were assessed in patients before interferon alpha and lamivudine therapy to determine if any pretreatment immunological parameter could be an indicator of response to therapy in childhood chronic hepatitis B infection. METHODS: Forty-four patients with chronic hepatitis B virus infection, aged 9.0 +/- 3.9 years, were enrolled in the study. The pretreatment clinical features, biochemical test results, histological activity indexes and immunological parameters were evaluated. All patients received interferon alpha for 6 months and lamivudine for 52 weeks. Four patients who could not be followed up were excluded from the study. The other 40 patients have been followed for a mean period of 27.5 +/- 9.7 months after therapy discontinuation. RESULTS: Seventeen patients showed loss of hepatitis B early antigen (HBeAg) with appearance of anti-HBe (42.5%) and six of those who responded also showed loss of hepatitis B surface antigen (HBsAg) with the presence of anti-HBs (15%). Except elevated aspartate aminotransferase levels, there was no significantly correlation between response and sex, age, pretreatment duration of disease and histological activity indexes. Pretreatment immunoglobulins (Ig), IgG subclasses, complement C3, C4 and secretory IgA levels were also not found to be significantly related to response. The evaluation of lymphocyte subsets showed that therapy responders had significantly reduced pretreatment ratios of CD4/CD8+ lymphocytes due to prominent increased percentages of CD8+ cells. The other cellular immunity parameters and some cell surface adhesion molecules were similar in both groups. CONCLUSION: This study emphasizes the importance of increased pretreatment CD8+ lymphocyte percentages leading to a significant decrease in CD4/CD8 ratio in chronic hepatitis B virus infection of childhood as an immunological factor predicting response to treatment.     

Evaluation of t-PA, PAI-2, IL-1beta and PGE(2) in gingival crevicular fluid of rheumatoid arthritis patients with periodontal disease

AIMS: This study was undertaken to compare periodontal conditions, gingival crevicular fluid (GCF) levels of tissue-type plasminogen activator (t-PA), its inhibitor plasminogen activator inhibitor-2 (PAI-2), interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)) in rheumatoid arthritis (RA) patients and control groups. METHODS: Twenty-three RA patients, 17 systemically healthy patients with periodontal disease (PD), and 17 systemically and periodontally healthy subjects were recruited. GCF samples were obtained from two single-rooted teeth. Full-mouth clinical periodontal measurements were recorded at six sites/tooth. GCF samples were analysed using relevant ELISA kits. Data were tested statistically by appropriate tests. RESULTS: Total amounts of t-PA, PAI-2 and PGE(2) in GCF samples of the healthy control group were significantly lower than the other groups (p<0.05). The RA group exhibited a higher total amount of t-PA in GCF samples than the PD group (p<0.05). PAI-2, IL-1beta and PGE(2) total amounts were similar in RA and PD groups (p>0.05). CONCLUSION: The coexistence of RA and periodontitis does not seem to affect clinical periodontal findings or systemic markers of RA. Similar inflammatory mediator levels in RA and PD groups, despite the long-term usage of corticosteroids, non-steroidal anti-inflammatory drugs, suggest that RA patients may have a propensity to overproduce these inflammatory mediators.     

Hyper-immunoglobulin M syndrome type 3 with normal CD40 cell surface expression

Mutations of the CD40 gene have been found in patients with autosomal recessive hyper-immunoglobulin M (HIGM) syndrome type 3. Five patients from four unrelated families with CD40 mutation have been reported so far. Clinical manifestations include recurrent sinopulmonary infections, Pneumocystis carinii pneumonia and Cryptosporidium parvum infection. Affected patients typically have very low levels of IgG and IgA and normal or high levels of IgM. Flow cytometry analysis of these five patients demonstrated that peripheral blood B lymphocytes lacked expression of surface CD40. Herein, we present two siblings from second-degree consanguineous Turkish parents with homozygous CD40 deletion of four nucleotides including the stop codon resulting presumably to a longer protein. Clinical and immunological profile of these patients is similar to the already reported HIGM3 patients except normal CD40 expression on B lymphocytes. This observation emphasizes the requirement of CD40 mutation analysis for definite diagnosis of HIGM3 despite normal flow cytometric expression of CD40, particularly if the immunological and clinical profile is suggestive for HIGM3.     

Serum immunoglobulins, IgG subclasses, isohemagglutinins and complement-3 levels in patients with thalassemia major

Serum IgG, IgM, IgA, IgG subclasses (IgG1, G2, G3, G4), isohemagglutinins and complement-3 concentrations were measured in 23 beta-thalassemic patients suffering from recurrent infections. No significant abnormalities were found in these humoral immunity investigations, both in splenectomized and non-splenectomized patients. On the other hand, iron overload or repeated blood transfusions were not found to down-regulate the humoral immune system of thalassemic patients.     

New laboratory findings in Turkish patients with transient hypogammaglobulinemia of infancy

Transient hypogammaglobulinemia (THI) of infancy is a common primary immunodeficiency usually resolves by 3 years of age. In this study, clinical, immunological data and outcome of 101 retrospectively diagnosed THI patients were evaluated. Majority of them suffered from recurrent respiratory infections (70.3%). Initial IgG, IgM and IgA levels were 446.7±121.5, 67.5±32.8, and 25.6±16.8 mg/dl, respectively. Patients who had lower IgG levels on admission reached normal IgG levels earlier than others. Infants who were retarded to reach age-related normal levels for IgM and IgA were found to have higher CD3+CD8+ T cells on admission. During immunoglobulin abnormalities, mean lymphocyte subset percentages and absolute counts were normal. Mean percentage of CD19+CD27+ memory B cells was 3.4±1.4% which is not significantly different from healthy children. Most of the children had protective antibody responses to tetanus (87%) and Haemophilus influenzae type B (85.7%) vaccines. Patients with low anti-tetanus responses had higher initial natural killer (NK) cell percentages probably due to recurrent viral infections or relative dominance of innate responses. Follow-up of patients with initially high NK were found to have longer duration of deficiency hence these patients' recoveries were delayed. During follow-up, 91/101 (90.1%) children produced normali levels of IgG at the end of 29.2 ± 15.2 months. The results of this study indicate that some children will achieve normal levels of IgG within 30 months of age, and some will remain IgG subclass or IgA deficient. Determination of increased NK percentages in patients with non-protective vaccine response and normal percentages of memory B cells are noteworthy novel findings.