[AIRE gene mutation in polyglandular syndrome type 1]. / Mutación del gen AIRE en el síndrome poliglandular tipo I.

Autoimmune polyglandular syndrome type 1 (APS-1) is an autosomal recessive disorder characterized by chronic mucocutaneous candidiasis, autoimmune hypoparathyroidism, and primary adrenal insufficiency. It has recently been associated with mutations of a single gene found on chromosome 21, designated AutoImmune Regulator (AIRE). We report two patients with APS-1 referred to our hospital for evaluation. The first patient was an 11-year-old girl with hypoparathyroidism, infectious or immunological malabsorption, and autoimmune hepatitis. Hypoparathyroidism associated with other processes with a probable autoimmune origin suggested APS-1. Genetic study was performed revealing deletion of 13 base pairs in exon 8 of the AIRE gene. The second patient was a 17-year-old girl with autoimmune hepatitis, hypoparathyroidism, mucocutaneous candidiasis, nail dystrophy, and obliterating bronchiolitis with a probable autoimmune origin. We suspected APS-1 and genetic study was performed. The only finding was an AIRE gene polymorphism. In conclusion, the presence of a single disease criterion is sufficient to suspect APS-1 and to indicate genetic study. Further studies are required to confirm the involvement of other genes in the development of this disease.

Autoantibodies in patients with IgA and IgG2 deficiencies.

Patients with primary immunodeficiencies have a high incidence of autoantibodies, mainly of no clinical significance. It has recently been suggested that patients with a combined IgA-IgG2 deficiency have more autoantibodies than those patients with isolated deficiencies. We have studied 42 patients with selective IgA deficiency, nine with isolated IgG2 deficiency and 13 with combined IgA-IgG2 deficiency, and have found that the combined IgA-IgG2 deficiency has no influence on autoantibody prevalence, except for anti-IgA antibodies. The presence of chronic respiratory infections (a clinical feature commonly associated with both selective IgA and IgG2 deficiencies) is unrelated to the prevalence of autoantibodies. The most frequent autoantibodies found are anti-IgA and anti-cardiolipin. Most of the autoantibodies have been found to be devoid of actual clinical significance. Only three patients had overt autoimmune disease.

[Usefulness of intracoronary therapy with progenitor cells in patients with dilated cardiomyopathy: Bridge or alternative to heart transplantation?]. / Utilidad de la terapia intracoronaria con células progenitoras en pacientes con miocardiopatía dilatada: ¿puente o alternativa al trasplante cardiaco?

INTRODUCTION AND OBJECTIVES: Some paediatric publications have recently raised the value of intracoronary therapy with autologous bone marrow-derived progenitor cells (APCs) in children with dilated cardiomyopathy (DCM) and heart failure. We describe the usefulness of this treatment in two infants with severe DCM and heart failure, who had been transferred to our hospital for cardiac transplant evaluation. PATIENTS AND METHODS: The first patient was a 3 months old male weighing 4 kg. The second was a 4 months old male weighing 5 kg. At the time of admission, both were in poor clinical condition (NYHA IV), with severe dilation and systolic dysfunction (ejection fraction [EF]<30%) of the left ventricle and marked elevation of NT-proBNP, requiring treatment with mechanical ventilation and inotropic iv infusion. After mobilization with G-CSF for 4 days, APCs were obtained from peripheral blood by leukocytapheresis, administering them by a slow intracoronary bolus injection using a stop-flow technique (6.15x106 CD34-positive cells/Kg in the first patient, and 10.55x106 CD34-positive cells/Kg in the second). RESULTS: Since the first week after the procedure, clinical status of patients improved and echocardiography showed a decrease in left ventricular dilation. A month later, there was a significant improvement in EF (> 40%) and NT-proBNP levels, subsequently maintained throughout the follow-up. However, four months later in the first patient, the left ventricle dilated again and its function slightly worsened, but without any significant impact in his clinical status. CONCLUSIONS: Intracoronary therapy with APCs can be an alternative in children, especially infants, with DCM and heart failure. It can reduce the waiting list mortality, improve clinical status and provide more time on the waiting list to receive a suitable organ, or even to make transplantation unnecessary.

Antiperinuclear factor: a useful test for the diagnosis of rheumatoid arthritis.

The objective of this study was to determine: (1) the diagnostic value of antiperinuclear factor (APF), (2) the types of immunoglobulins involved in the reaction and (3) the presence of the antibody in paired samples of serum and synovial fluid (SF). We studied 408 serum samples from the following: healthy controls (n = 68), patients with rheumatoid arthritis RA; n = 160, 106 RF-positive and 54 RF-negative and patients with other rheumatic diseases (n = 180). We examined paired serum and SF samples in 27 patients (8 with RA and 19 with other rheumatic conditions). APF was determined by an indirect immunofluorescence assay. A group of 30 APF-positive serum samples was incubated with fluorescent-labelled antisera against IgG, IgM and IgA independently. APF was positive in 55.7% of patients with RF-positive RA, in 35.2% of patients with RF-negative RA, in 11.1% of patients with other rheumatic diseases and in 5.9% of healthy controls. Statistical differences were found between RF-positive RA and the other three groups (P = 0.02, P = 0.0001, P = 0.0001, respectively) and between RF-negative RA and the groups of other rheumatic diseases (P = 0.0001) and healthy controls (P = 0.005). The specificity of the test for RA was 90.2%. APF was present in three SF samples from RA patients (37.5%). The reaction was mediated by immunoglobulins of the IgG class in 100% of those tested, and, in addition, 30% were of IgA and 6.7% of IgM classes. We concluded that APF is a good diagnostic test that could be included in the classification criteria of RA, it can be present in SF and it is predominantly an antibody of the IgG class.

Antiperinuclear factor as a prognostic marker in rheumatoid arthritis.

OBJECTIVE: Antiperinuclear factor (APF) is an autoantibody detected in >50% of patients with rheumatoid arthritis (RA); it shows a specificity of roughly 90%. We investigated the possible role of APF as a prognostic marker in RA. METHODS: A series of 103 patients with RA who fulfilled the 1987 American College of Rheumatology criteria (88 women and 15 men; mean age 55.5 yrs, mean disease duration 9 yrs) were prospectively followed. Sixteen variables were assessed in each patient at inclusion and over a 3 year period. APF was determined by indirect immunofluorescence assay using human buccal mucosal cells as substrate. APF assays were done at entry and at the end of followup without knowledge of the clinical status of the patients. Mann-Whitney U, chi-squared tests, variance analysis, and kappa index were used for statistical analysis. RESULTS: Eighty of 103 patients completed followup. APF was detected in 40 of 80. At inclusion, APF correlated with the visual analog scale (VAS) of pain (p = 0.02). However, patients who showed APF positivity at entry had a less favorable course than APF negative individuals, as shown by a worse VAS of well being (p = 0.01), Ritchie index (p = 0.01), number of painful joints (p = 0.03), grip strength (p = 0.01), C-reactive protein (p = 0.04), and Health Assessment Questionnaire score (p = 0.03) at the end of the study. In addition, APF positive patients showed a worse radiological course (p = 0.03). CONCLUSION: Our results suggest APF is a possible marker of poor prognosis in RA.

[New indications for gamma globulins]. / Nuevas indicaciones de las gammaglobulinas.

Intravenous immunoglobulin (IV Ig) has been shown its therapeutic value in primary immunodeficiency diseases associated with a profound impairement of IgG-mediated antibody production. In recent years its range of indications has been extended to some secondary immunodeficiency disorders such as chronic lymphocytic leukemia and children with symptomatic HIV infection IV Ig is also of value in cytomegalovirus infection in transplant recipients. The use of IV Ig in some immunoregulatory disorders, namely immune thrombocytopenic purpura and Kawasaki syndrome has also been proved. Preliminary studies suggests a benefit in myasthenia gravis, Guillain-Barré syndrome, polymyositis, chronic demyelinating diseases and steroid dependent asthma. Little is known about the mechanism of action of IV Ig in these immunoregulatory disorders. In sum, IV Ig has a few proved indications and many potential ones. Carefully controlled clinical trials are needed to determine the effectiveness of IV Ig in these conditions.