Could immune cells be associated with nephropathy in Fabry disease patients?

BACKGROUND: In Fabry Disease (FD), although the primary factor initiating kidney damage is glycosphingolipid accumulation, secondary conditions such as increased inflammation and fibrosis may cause this damage to progress. These processes may be induced by immune cells. Therefore, we aimed to investigate the peripheral lymphocyte subgroup analysis of the patients with FD and compare these results with healthy individuals. In addition, we performed T, B, NK, and plasma cell analyses in kidney biopsy materials and compared these kidney biopsy results with the biopsy results of patients whose kidney functions were impaired after 4 years of regular ERT. MATERIALS AND METHODS: 18 FD and 16 healthy individuals were included in the study. T-B lymphocyte and NK-cell populations were determined. We performed kidney biopsies (KBx) on 13 patients with FD prior to ERT. Of these, 4 patients had rebiopsy after 4 years of regular ERT. Immunohistochemical staining was performed to define immune cell infiltration. RESULTS: There was no statistically significant difference in terms of total, helper and cytotoxic T-lymphocyte and CD3-CD16+CD56+ natural killer (NK)-cell count (p = 0.20; p = 0.12; p = 0.76; p = 0.75, respectively).According to KBx findings prior to ERT, all patients had interstitial fibrosis (IF), podocyte vacuoles (PV), and podocyte inclusion (PI), CD3, CD4, CD8, CD16, and CD56 positivity at different levels. None of the patients had CD19, CD20, and CD138 positivity at the first biopsies. When we compared the first and the second KBx results of the two progressors, we also demonstrated that CD3+4+T-cells infiltration remained the same, whereas CD8+T cells, CD16+ and 56+NK-cells infiltration were significantly decreased. In contrast, CD20+B cells and CD138+plasma cell infiltration were significantly increased despite 4 years of ERT (15 fold and sixfold, respectively). The CD20+B and CD138+ plasma cells and IF were positively correlated with proteinuria. CONCLUSIONS: The progression of FD nephropathy and proteinuria is increased despite a long-term ERT. Immune cells, primarily B and plasma cells, might cause these unwanted consequences.

CD3G gene defects in familial autoimmune thyroiditis.

The patients with CD3γ deficiency can present with different clinical findings despite having the same homozygous mutation. We report three new CD3gamma-deficient siblings from a consanguineous family with a combined T-B+NK+ immunodeficiency and their variable clinical and cellular phenotypes despite the same homozygous mutation of the CD3G gene (c.80-1G>C). We also re-evaluate a previously reported non-consanguineous family with two CD3gamma-deficient siblings with the same mutation. The median age at diagnosis was 11 years (14 months-20 years). We found all five patients to display autoimmunity: autoimmune thyroiditis (n = 5), autoimmune haemolytic anaemia (n = 2), immune thrombocytopenia (n = 1), autoimmune hepatitis (n = 1), minimal change nephrotic syndrome (n = 1), vitiligo (n = 1) and positive antinuclear antibodies (n = 3) as well as high IgE (n = 2) and atopic eczema (n = 2). While CD3(+) TCRαß+T cell percentages were low in all patients, only one had lymphopenia and 3 had CD3(+) T cell lymphopenia. Strikingly, we report frequent and multiple autoimmunity in tested heterozygous carriers in both families (n = 6; in 67%), and frequent autoimmunity in family members not available for testing (n = 5, in 80%). The results suggest that CD3G should be studied as a candidate gene for autoimmunity and that CD3gamma deficiency should be considered among other primary immunodeficiencies with predominantly autoimmune manifestations.

Association of Tourette syndrome and obsessive-compulsive disorder with allergic diseases in children and adolescents: a preliminary study.

OBJECTIVES: To investigate the rate of allergic diseases including asthma, allergic rhinitis and eczema in children and adolescents diagnosed with obsessive-compulsive disorder (OCD) (n:26) and/or Tourette syndrome (TS) (n:32) [OCD plus TS, n:13] compared to control subjects (n:35) [total, n:80]. PATIENTS AND METHODS: The symptoms of any allergic disease were assessed using the ISAAC questionnaire form. Allergy diagnoses were made by a pediatric allergy specialist. Skin prick tests were applied, and IgE levels and eosinophil counts were measured. RESULTS: While only one-fifth of the control subjects had allergic diseases, more than half of the children with TS and/or OCD had comorbid allergic diseases. Positive skin prick tests were greater in OCD patients compared to control subjects. There were no significant differences between the groups in terms of eosinophil counts or IgE levels. Among the allergic diseases, while allergic rhinitis was diagnosed at significantly higher rates in TS patients, eczema was significantly higher in OCD patients compared to control subjects. CONCLUSIONS: This preliminary study shows an association between allergic diseases and TS and/or OCD. The results revealing differences in associations between types of allergic disease (rhinitis or eczema) and neuropsychiatric disorder (tic disorder or OCD) need to be investigated in further studies with higher numbers of participants, and immune markers should be examined.

The prevalences of allergic diseases in rural and urban areas are similar

Background: In this study, we aimed to detect the influence of environmental and socioeconomic factors for asthma, allergic rhinitis, and eczema among children aged 6-18 years. Method: Two each of schools located in urban and in rural areas were included in the study. Children in these schools were asked to respond to 32 questions in total, including demographic and socioeconomic features and the questions of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire form. Results: The average age of children included in the study was 11.5 ± 3.3 years, and the ratio ofboys (55.4%) to girls (44.6%) was 1.2/1. The prevalence of asthma was found as 11.5%, allergic rhinitis as 22.1%, and eczema as 10.7%. Asthma (21.9%), allergic rhinitis (44.3%) and eczema (19.8%) were more frequent in cases which had family history of atopy (p < 0.001). Although there were differences between regions regarding income and educational levels, number of persons in the household, duration of breast feeding, and dietary habits, these variants were found inconclusive for the development of asthma. The risk of progression to asthma and atopic diseases decreased as age increased and the educational level of the father increased. Conclusion: According to our results, atopic diseases can be considered frequent in Konya, history of atopy in the family is the most predictive factor and the effects of rural or urban factors are not obvious in atopic disease development (AU)

The prevalences of allergic diseases in rural and urban areas are similar.

BACKGROUND: In this study, we aimed to detect the influence of environmental and socioeconomic factors for asthma, allergic rhinitis, and eczema among children aged 6-18 years. METHOD: Two each of schools located in urban and in rural areas were included in the study. Children in these schools were asked to respond to 32 questions in total, including demographic and socioeconomic features and the questions of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire form. RESULTS: The average age of children included in the study was 11.5 ± 3.3 years, and the ratio of boys (55.4%) to girls (44.6%) was 1.2/1. The prevalence of asthma was found as 11.5%, allergic rhinitis as 22.1%, and eczema as 10.7%. Asthma (21.9%), allergic rhinitis (44.3%) and eczema (19.8%) were more frequent in cases which had family history of atopy (p < 0.001). Although there were differences between regions regarding income and educational levels, number of persons in the household, duration of breast feeding, and dietary habits, these variants were found inconclusive for the development of asthma. The risk of progression to asthma and atopic diseases decreased as age increased and the educational level of the father increased. CONCLUSION: According to our results, atopic diseases can be considered frequent in Konya, history of atopy in the family is the most predictive factor and the effects of rural or urban factors are not obvious in atopic disease development.