Prevalence of antibodies to ganglioside and Hep 2 in Gaucher, Niemann - Pick type C and Sanfilippo diseases.

Lysosomal Storage Diseases (LSDs) are rare genetic diseases, the majority of which are caused by specific lysosomal enzyme deficiencies and all are characterized by malfunctioning lysosomes. Lysosomes are key regulators of many different cellular processes and are vital for the function of the immune system. Several studies have shown the coexistence of LSDs and immune abnormalities. In this study, we investigated the presence of autoantibodies in the plasma of patients with Gaucher disease (GD; n = 6), Sanfilippo Syndrome B (SFB; n = 8) and Niemann - Pick type C disease (NPC; n = 5) before and following Miglustat treatment (n = 3). All were examined for antibodies to antigens of Hep-2 cells and antiganglioside antibodies (AGSA). No autoantibodies were detected in GD patients. 3/8 SFB patients showed only AGSA (2/3 IgM / IgG; 1/3 IgG), 3/8 only anti-Sm E/F and 2/8 showed both IgM / IgG or IgG AGSA and anti-Sm E/F. 3/5 NPC patients showed AGSA (2/3 IgM and IgG, 1/3 IgM) and one anti-Sm E/F and IgM AGSA. Following treatment one patient with no AGSA developed IgM AGSA and two with both IgG and IgM showed only IgG AGSA. In our study, investigating similar numbers of patients, autoantibodies were observed in NPC and SFB patients but not in GD patients. Our findings suggest that, independently of the development of an autoimmune disease in patients with LSDs, there seems to be an autoimmune activation that differs in different disorders. Further studies including more patients, also at different stages of disease and treatment, are needed in order to get further insight into the immune irregularities associated with different LSDs and their significance.

Primary immunodeficiency diseases: a 30-year patient registry from the referral center for primary immunodeficiencies in Greece.

Primary Immunodeficiencies (PID) represent a group of heterogeneous immune diseases with important biological significance. We reviewed the records of children diagnosed with PID in the Referral Center for PID in our country in order to describe the epidemiological, clinical and laboratory characteristics of immunodeficient patients. During a 30-year period, 147 patients (101 males, 68.7 %), with a mean age of 6.5 years at the time of diagnosis, were diagnosed with PID. The most prevalent diagnoses of PID were: "Combined Immunodeficiency" in 46 (31.3 %) patients, "Well-defined immunodeficiency syndrome" in 35 (23.1 %) patients, "Predominantly antibody deficiency" in 30 (20.4 %) patients and "Congenital defect of phagocyte function or both" in 28 (19 %) patients. There was a higher prevalence of males with "Combined immunodeficiency" (p < 0.033) and "Predominantly antibody deficiency" (p < 0.02) compared to females. The median age of children at the onset of symptoms and at the time of diagnosis was 0.5y (IQR: 0.1-2.5) and 2y (IQR: 0.6-7.2), respectively. The median diagnostic delay was 0.9y (IQR: 0.2-4.8). This period was shorter for patients with "Combined immunodeficiency" [median 0.3y (IQR: 0.1-1)], and longer for those with "Predominantly antibody deficiency" [median 3.2y (IQR: 0.2-5.9) or "Disease of immune dysregulation" [median 3.2y (IQR: 0.1-6.6)]. Comparing the rates in our population with those of the European Registry (ESID), the rates of "Combined immunodeficiencies", "Well-defined syndromes" and "Congenital birth defects and/or function of phagocytes" were significantly higher in this study (p <0,001). PID registry analysis improves knowledge in the field of Immunology and enhances awareness, early detection, diagnosis, and management of this rare but significant group of diseases.

Flow cytometric analysis of the CD4+ TCR Vß repertoire in the peripheral blood of children with type 1 diabetes mellitus, systemic lupus erythematosus and age-matched healthy controls.

BACKGROUND: Data regarding the quantitative expression of TCR Vß subpopulations in children with autoimmune diseases provided interesting and sometimes conflicting results. The aim of the present study was to assess by comparative flow cytometric analysis the peripheral blood CD4+ TCR Vß repertoire of children with an organ-specific autoimmune disorder, such as type 1 diabetes mellitus (T1DM), in comparison to children with a systemic autoimmune disease, such as Systemic Lupus Erythematosus (SLE) in comparison to healthy age-matched controls of the same ethnic origin. The CD4+ TCR Vß repertoire was analysed by flow cytometry in three groups of participants: a) fifteen newly diagnosed children with T1DM (mean age: 9.2 ± 4.78 years old), b) nine newly diagnosed children with SLE, positive for ANA and anti-dsDNA, prior to treatment (mean age: 12.8 ±1.76 years old) and c) 31 healthy age-matched controls (mean age: 6.58 ± 3.65 years old), all of Hellenic origin. RESULTS: CD4 + TCR Vß abnormalities (± 3SD of controls) were observed mainly in SLE patients. Statistical analysis revealed that the CD4 + Vß4 chain was significantly increased in patients with T1DM (p < 0.001), whereas CD4 + Vß16 one was significantly increased in SLE patients (p < 0.001) compared to controls. CONCLUSIONS: CD4 + Vß4 and CD4 + Vß16 chains could be possibly involved in the cascade of events precipitating the pathogenesis of T1DM and SLE in children, respectively.

Factors for thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with an autoimmune reaction to thyroid antigens including thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg). AIMS: We determined in children with T1DM the relationship of positive anti-thyroid antibodies to potential risk factors, including, age, gender, duration of diabetes, and glutamic acid decarboxylase antibodies (anti-GAD). MATERIALS AND METHODS: We studied 144 children and adolescents with T1DM. Their age was 12.3 +/- 4.6 (mean +/- SD) years, and duration of diabetes was 4.6 +/- 3.8 years. Anti-thyroid antibodies were determined using a luminescence method and anti-GAD using an enzyme-linked immunosorbent assay. RESULTS: The prevalence rates of anti-thyroid antibodies among the children with T1DM in our study were: anti-TPO (17.4%), anti-Tg (11.1%), and of both anti-thyroid antibodies (10.4%). The presence of serum anti-thyroid antibodies was positively associated with age (16.6 years in those with positive tests versus 12.0 years in those with negative tests, P = 0.027), duration of diabetes (7.4 versus 4.3 years, P = 0.031), and serum TSH (Thyroid-stimulating hormone) levels (4.8 versus 2.3 microIU/mL, P = 0.002). The presence of both anti-thyroid antibodies was associated with female sex (boys: 4/75 (5.3%), girls: 11/69 (15.9%), chi-square = 6.44, P = 0.04). Subclinical autoimmune thyroiditis (SAIT) was present in 55.5% of the patients with thyroid antibody-positivity and was positively associated with age (16.6 versus 12.0 years, P = 0.001) and diabetes duration (7.6 versus 4.2 years, P = 0.001). Multiple logistic regression analysis revealed that the development of anti-thyroid antibodies was predicted by: 1) the presence of anti-GAD (odds ratio (OR) 1.45, 95% confidence interval (CI) 1.09-1.92), 2) the presence of a second anti-thyroid antibody (OR 134.4, 95% CI 7.7-2350.3), and 3) older age (OR 22.9, 95% CI 1.13-463.2). CONCLUSIONS: Thyroid autoimmunity was associated with female gender, increasing age, long diabetes duration, the persistence of anti-GAD, and with TSH elevation, indicating subclinical hypothyroidism.

Screening for associated autoimmunity in children and adolescents with type 1 diabetes mellitus (T1DM).

BACKGROUND/AIMS: Type 1 diabetes (T1DM) is associated with autoimmune thyroid, celiac, autoimmune gastric and Addison's disease. Our aim was to investigate the prevalence of associated autoantibodies in relation to the demographic and beta-cell autoantibody status (anti-GAD). METHODS: Antibodies against thyroid peroxidase (anti-TPO), thyroglobulin (anti-Tg), tissue transglutaminase (anti-tTG IgA), parietal cells (APCA) and adrenal tissue (AAA) were measured in 144 children with T1DM with a mean +/- SD age of 12.3 +/- 4.6 years and a diabetes duration of 4.6 +/- 3.8 years. RESULTS: The prevalence of antibody positivity among our patients was: anti-GAD 53.2%, anti-thyroid (anti-TPO 17.4%, anti-Tg 11.1%); anti-tTG IgA 7.6%, APCA 4.0%, and AAA 0%. Among the children with positive anti-thyroid antibodies, 60% developed autoimmune thyroiditis, while among those anti-tTG IgA positive, 62.5% developed biopsy-confirmed celiac disease. Female gender was more frequent among anti-tTG IgA-positive patients (OR 4.47, p = 0.068), while increasing age was associated with anti-Tg positivity (OR 22.9, p = 0.041). The presence of anti-thyroid antibodies was associated with the presence of anti-GAD (OR 1.45, p = 0.01) and parietal cell antibodies (OR 4.98, p = 0.09). CONCLUSION: Among T1DM patients, the prevalence rates of anti-thyroid and parietal cell antibodies increased with age and diabetes duration. As the presence of anti-GAD was associated with gastric and thyroid autoimmunity, it could serve as marker for the development of additional autoimmunity in adolescents with diabetes.