Andres Franco

T cell activity in successful treatment of chronic urticaria with omalizumab

Omalizumab, a humanized monoclonal anti-IgE antibody has the potential to alter allergen processing. Recently, it has been postulated the assessment of PHA-stimulated adenosine triphosphate (ATP) activity as maker of CD4+ T cells activity in peripheral blood cells. We present the case report of a 35-year-old woman with a history of chronic idiopathic urticaria and angioedema of 8 years of development with poor response to treatment. The patient was partially controlled with cyclosporine at doses of 100 mg/12 h. However, she was still developing hives daily. Finally treatment with omalizumab was started at dose of 300 mg every 2 weeks. The patient experienced a decrease in urticarial lesions 2 days after starting therapy. We also evaluated the effects of omalizumab therapy on the activity of peripheral blood CD4+ T cells from the patient, in order to determine the potential modification of anti-IgE therapy on the process of antigen presentation-recognition. Activity of CD4+ cells by ATP release was clearly increased demonstrating an enlarged CD4 activity. Omalizumab may be useful in the treatment of severe chronic urticaria. ATP activity of peripheral blood CD4+ T cells might be a non-subjective method to assess Omalizumab activity.

Downregulation of Angiogenesis Factors, VEGF and PDGF, after Rapid IgE Desensitization and Oral Immunotherapy in Children with Food Allergy

Background. Angiogenesis has a key role in several conditions and is regulated by several factors such as the platelet-derived growth factor (PDGF) or the vascular endothelial growth factor (VEGF). The goal of this study was to investigate the possible role of PDGF and VEGF in a group of patients with severe food allergy. Methods. We design a prospective longitudinal study (n = 30) with patients with persistent cows milk proteins (CMP) allergy. After achieving a CMP rush desensitization protocol, a clinical followup including SPT and blood samples to determine sIgE, protein levels, PDGF, and VEGF-A and a panel of the most representative Th1, Th2, Treg, and Th17 cytokines were also monitored. Results. Baseline levels of PDGF and VEGF in the CMP allergic patients (1170 pg/mL and 253 pg/mL) were different compared to those nonallergic CMP control subjects (501 pg/mL and 108 pg/mL). Both PDGF and VEGF were significantly downregulated (P < 0.05) 6 months after completion of the CMP desensitization process and remained significantly decreased 12 months later. Conclusion. The present study shows a significant increase of PDGF and VEGF in anaphylaxis suffering children compared to a control group. Interestingly, both VEGF and PDGF were significantly downregulated after completing a full CMP rush IgE desensitization.

Isolated Ro52 Antibodies as Immunological Marker of a Mild Phenotype of Undifferentiated Connective Tissue Diseases

The term undifferentiated connective tissue disease (UCTD) is used to describe undiagnosed patients that do not fulfill classification criteria for definite connective tissue disease (Systemic Lupus, Systemic Sclerosis, Sjögren Syndrome, and Dermatomyositis/Polymyositis). It is important to find serological markers as predictors of the evolution or severity of these diseases. The objective of this retrospective study was to investigate if there was a milder subgroup of UCTD with a special clinical profile consisting only in the presence of anti-Ro52 autoantibodies. Immunological and clinical records of 62 patients attending the hospital during 30 months were studied. Results showed a target population formed by mostly women, aged between 40 and 80 years at the moment of the study, with a registered age of onset between 40 and 60 years. Speckled pattern was the most frequent pattern found by indirect immunofluorescence. Given the obtained results and keeping in mind possible limitations because of sample size, isolated positive anti-Ro52 autoantibodies seem to lead to a benign effect in terms of evolution of the disease. As a future objective, the follow-up of these patients should be necessary to investigate new clinical symptoms, serological markers, or development of a definite connective tissue disease over time.

IP-10 In Pediatric Celiac Disease and Food Allergy.

physicians and pharmaceutical companies that PML could occur. Th is brings us to the topic of the biological plausibility of the rare event of PML in association with anti-adhesion therapies. We off er as a cautionary example the unexpected immunologic eff ect of serum antibodies to Abciximab. Th is monoclonal antibody therapy was designed to bind to the activated form of platelet glycoprotein IIb / IIIa (aka integrin α IIb β 3 ), and prevent clotting during endovascular procedures without an excess of clinically important bleeding in most patients. However, some patients developed antibodies against the abciximab / platelet complex, which reduced the specifi city of this interaction ( 3 ). When one of these rare patients is treated with abciximab, severe thrombocytopenia occurs, and rapid bleeding from all mucosal surfaces ensues. Although it is unlikely that a similar mechanism might reduce the specifi city of other antiintegrin monoclonal therapies, it is not impossible. Th at this has previously occurred in patients treated with another anti-integrin monoclonal antibody, and that patients with infl ammatory bowel disease (IBD) are prone to autoimmune reactions, makes it unlikely but possible that an unforeseen mechanism in rare patients could reduce the specifi city of an antiα 4 β 7 monoclonal therapy ( Figure 1 ). Suffi cient sample size can change a very rare event to a reasonably likely event. We would like to reiterate that the rule of 3 s provides the upper limit of the 95 % confi dence interval, not the actual estimate of the risk of an event. We agree with the letter writers that PML cases associated with vedolizumab, if they occur at all, will be rare events, and that there are many factors that could aff ect an estimate of the frequency of rare events, including biological plausibility, latency, and other risk factors. We are hopeful that anti-adhesion therapies will prove benefi cial to millions of patients with IBD worldwide, but we should be prepared for the possibility of rare events, including PML. We hope that if PML does occur in the future in association with the newer anti-adhesion therapies, gastroenterologists, the Food and Drug Administration, and the general public will thoughtfully consider the frequency of rare events and embrace the richness of human diversity. To paraphrase Miranda in Shakespeare ’ s Th e Tempest (V,i), O brave new world, that has such biologic processes in it! To dismiss the past (abciximab) and deny the possibility of rare risks in the future would make us ill-prepared for an important potential complication. As vedolizumab leaves the island of clinical trials for the wider world of clinical practice, rare events might occur, but we should not panic or overreact to them. Instead, we should thoughtfully consider the frequency and magnitude of benefi ts in relation to the frequency and magnitude of rare risks .