Biomedical subjects
Alejandro Malbran
Publications and source records attributed to Alejandro Malbran.
[Chronic urticaria with alterations of the thyroid function and thyroid peroxidase antibodies].
Chronic urticaria is a frequent pathology, characterized by the presence of hives and/or angioedema lasting longer than 6 weeks. In an important number of patients it behaves as an autoimmune illness, frequently associated with alterations in thyroid function and thyroid antibodies. We herein describe a consecutive series of 70 patients with a diagnosis of chronic urticaria. Seven (10%) had a diagnosis of thyroid illness previous to their first consultation. Thyroid function and thyroid antibodies were studied in the remaining 63 patients by measuring the level of serum thyrotropin and the titer of peroxidase antibodies. Abnormal thyrotropin levels were detected in 11 (17%) patients, who in conjunction with the 7 patients with previous thyroid illness, add up to 18 (26%) with altered thyroid function. From 61 patients who were tested for thyroid peroxidase antibodies, 22 (36%) were positive. Of 57 patients without a diagnosis of previous thyroid disease, in whom both the levels of serum thyrotropin and the presence of thyroid peroxidase antibodies had been studied, 24 (42%) presented at least one altered study. Given the high percentage of thyroid alterations in our series of patients, it seems clinically relevant to study the thyroid function and the presence of thyroid peroxidase antibodies in patients with chronic urticaria.
Treatment of primary Epstein-Barr virus infection in patients with X-linked lymphoproliferative disease using B-cell-directed therapy.
X-linked lymphoproliferative disease (XLP) is a congenital immunodeficiency that is characterized by an abnormal immune response to primary Epstein-Barr virus (EBV) infection. After EBV exposure, affected patients often develop fulminant infectious mononucleosis (FIM), a life-threatening condition marked by the uncontrolled expansion and activation of T and B lymphocytes and macrophages. We hypothesized that the rapid elimination of B cells immediately following EBV exposure might reduce the severity of primary EBV infection in patients with XLP. To test this possibility, we administered the anti-CD20 antibody rituximab to 2 patients who presented with acute infection. Following treatment, both patients exhibited a complete resolution of symptoms and no longer demonstrated detectable EBV DNA within circulating lymphocytes. Moreover, neither patient has developed FIM or lymphoma in more than 2 years of follow-up. These data suggest that the pre-emptive use of B-cell-directed therapy may reduce the morbidity and mortality of primary EBV infection in XLP-affected individuals.
Loss of circulating CD27+ memory B cells and CCR4+ T cells occurring in association with elevated EBV loads in XLP patients surviving primary EBV infection.
Detailed longitudinal studies of patients with X-linked lymphoproliferative disease (XLP) may increase our understanding of the immunologic defects that contribute to the development of lymphoma and hypogammaglobulinemia in XLP. We describe progressive changes observed in immunoglobulin concentrations, lymphocyte subsets, and Epstein-Barr virus (EBV) loads occurring in a 2-year period in a newly infected, but otherwise healthy, carrier (patient 9). We compare these findings with those observed in the patient's brother, who had hypogammaglobulinemia and XLP (patient 4). Immunoglobulin G (IgG), IgM, and IgA concentrations increased in patient 9 during acute EBV infection, but thereafter they decreased steadily to concentrations consistent with hypogammaglobulinemia, reaching a plateau 5 months after infection. In both patients, CD19+ B-lymphocyte rates remained lower than 3%, with a contraction of the B-cell memory compartment (CD27+ CD19+/CD19+) to 20% (normal range, 32%-56%). T-lymphocyte subpopulations showed a reduction in CD4+ T-cell counts and a permanent CD8+ T-cell expansion. Interestingly, CXCR3 memory TH1 cells were expanded and CCR4+ TH2 lymphocytes were reduced, suggesting that abnormal skewing of memory T-cell subsets might contribute to reduced antibody synthesis. Despite an expanded number of CD3+CD8+ lymphocytes, increased EBV loads occurred in both patients without overt clinical symptoms of mononucleosis, lymphoproliferative disease, or lymphoma.