Primary Immunodeficiency Syndrome in Spain: First Report of the National Registry in Children and Adults

The Spanish Registry for Primary Immunodeficiency Diseases (REDIP) was organized in 1993. One thousand sixty-nine cases of primary immunodeficiency diseases (PID) were registered in patients diagnosed between January 1980 and December 1995. PID diagnosis was made according to the World Health Organization criteria. The most frequent disorders were IgA deficiency (n = 394) and common variable immunodeficiency (n = 213), followed by severe combined immunodeficiency (n = 61), C1 inhibitor deficiency (n = 52), X-Iinked agammaglobulinemia (n = 49), IgG subclass deficiency (n = 48), and chronic granulomatous disease (n = 32). A comparative study between REDIP and data recently obtained from the European registry (ESID Report, 1995) revealed important differences between phagocytic disorders and complement deficiencies reported in both registries, 4.9 vs 8.7 and 6.0 vs 3.6, while percentages of predominantly antibody deficiencies and T cell and combined deficiencies concurred with those reported in the European registry, 69.3 vs 64.7 and 14.7 vs 20.2, respectively. The heterogeneous nature of the geographical distribution of cases submitted may indicate underdiagnosis of PID in some country areas; surprisingly, the interval between the onset of clinical symptoms and diagnosis was significant, even in immunodeficiency diseases, such as IgA deficiency, which are easy to diagnose.     

Changes in IL-10 and specific antibodies associated to successful Dermatophagoides pteronyssinus immunotherapy in children during the first year of treatment

BackgroundAllergen-specific immunotherapy (SIT) is a long-term treatment of respiratory allergy.ObjectiveTo look for early predictors of the effectiveness of Dermatophagoides pteronyssinus SIT.MethodsA prospective multi-centre study was carried out in Spain. Children with D. pteronyssinus rhinitis or asthma were invited to participate. The study was divided into times: T0 (recruitment); T1 (inclusion); T2 a-f (immunotherapy times) and T3 (the end of study). Efficacy of SIT was assessed by clinical scores, visual analogue scales (VAS) and lung function tests. We performed D. pteronyssinus skin tests at T1 and T3, and determined specific serum IgE, IgG4 and IL-10 at T1, T2f and T3.Data were analysed using Mann–Whitney and Kruskal–Wallis tests, compared using Wilcoxon and Chi-square tests, and correlated to Spearman test. All tests had a significance level of 0.05.ResultsThirty-eight children completed the study. At T1 all had rhinitis and 34 also had asthma. At T3, 30 patients had improved, six experienced no changes and two worsened. Improvement was associated to FEV1/FVC and VAS improvement; to a reduction in D. pteronyssinus skin prick test; to a progressive increase in serum levels of D. pteronyssinus IgE, and D. pteronyssinus, Der p1 and Der p2 IgG4. IL-10 levels showed an early increase at T2f (the end of initial build-up immunotherapy phase), and then a reduction at T3 (the end of a year of immunotherapy).Improvement associated to an early increase in IL-10 and was correlated with VAS and specific IgG4 evolution.     

Vacuolating megalencephalic leukoencephalopathy with subcortical cysts: functional studies of novel variants in MLC1

Nine new unrelated patients presenting vacuolating myelinopathy with subcortical cysts were identified and analyzed for variations in the MLC1 gene. We detected 12 mutations (p.Leu37fs, p.Met80Val, p.Leu83Phe, p.Pro92Ser, p.Ser93Leu, p.Ile108fs, p.Gly130Arg, p.Cys171fs, p.Glu202Lys, p.Ser269Tyr, p.Ala275Asn, and p.Leu310_311insLeu) of which nine were novel. In one patient we did not detect mutations. Using a heterologous system, three new missense variants (p.Glu202Lys, p.Ser269Tyr, and p.Ala275Asn) and a single leucine insertion (p.Leu310insLeu)--lying in a stretch of seven leucines--were functionally assayed by determining total protein levels and mutant protein expression at the plasma membrane. No correlation was observed between mutation, clinical features, and plasma membrane expression of mutant protein.