Síndrome de hiper-IgM en miembros de 2 familias Chilenas no relacionadas: análisis genético- molecular / Hyper-IgM syndrome in members of two unrelated Chilean families: molecular and mutation analysis

BACKGROUND: Hyper-IgM syndronie (HIGM) is a rare primary immunodeficiency used to describe a heterogeneous group of disorders characterized by recurrey bacterial infrctions, normal or elevated serum IgM levels and low or absent serum IgG, IgA and IgE. AIM: To make definitive diagnosis, detect mutations in carriers and perform genetic counseling in patients with HIGM. PATIENTS AND METHODS: We studied the expression of CD40L, CD40 and made a mutation analysis of the CD40L gene in 3 males of 2 unrelated Chilean families diagnosed as a possible syndrome of hyper-IgM and 3 relatives. RESULTS: We identified a deletion frameshift in the exon 2 (delA225) of the extracellular domain of GD40L gene in one patient and verified the carrier stains of his mother and sister. The other patients showed a low expression of GD40L in activated T cells (65.3% ammd 65.5%) and a normal expressiomi of CD40. No alterations were found in the single strand conformation polymorphism analysis of the CD40L. CONCLUSIONS: These result allowed us to make a definite diagnosis of HIGM1 of a patient, detect female carriers and suggest a HIGM of recessive inheritance with normal CD40 expression in the patients of the second family.

Estudio del polimorfismos de receptores Fcylla en pacientes chilenos con lupus erimatoso sistémico / Polymorphisms of Fcylla receptors in chilean patients with systemic lupus erythematosus

Background: Polymorphisms of Fc receptors for IgG (FcgR) have been proposed as a genetic factor that influences susceptibility for systemic lupus erythematosus (SLE). Human FcgRIIa has 2 codominantly expressed alleles, H131 and R131, which differ at amino acid position 131 in the second extracelular domain (histidine or arginine respectively) and differ substantially in their ability to bind human IgG2. The H131 allele binds IgG2 efficiently, whereas R131 binds it poorly. Because IgG2 is a poor activator of the classical complement pathway, the H131 is essential for the disposal of IgG2 immune complexes. Aim: To determine the distribution of FcgRIIA genes in a cohort of Chilean SLE patients, with or without a history of lupus nephritis. Patients and methods: We studied 52 Chilean SLE patients fulfilling the 1982 American College of Rheumatology (ACR) criteria, 20 of whom had a history of nephritis, and 44 ethnically matched disease-free controls. FcgRIIa allotypes were genotyped by PCR. Results: No significant association was observed between the low affinity FcgRII receptor (FcgRIIa-R131) and the presence of SLE or lupus nephritis. However, genotype frequencies in SLE patients but not in controls, departed from the proportions predicted by the Hardy-Weinberg equilibrium, suggesting this locus might be related to the disease. Conclusions: Our results suggest that in Chilean patients with SLE, as well as in many other populations, the R131 allotype is not a major factor predisposing to the development of SLE or lupus nephritis