Από το τελευταίο τευχος του NEJM έρχεται σαν letter to the editor και η εξαιρετική δουλειά των Ισπανών συναδέλφων που συσχετίζει τα επίπεδα των MIP-1α και MCP-1 με την επιτυχή έκβαση απευαισθητοποίησης στο γάλα της Αγελάδος. Στον σύνδεσμο protocol μπορεί όποιος ενδιαφέρεται να “κατεβάσει” ελεύθερα την εργασία και το ενδιαφέρον πρωτόκολλο απευαισθητοποίσης που εφάρμοσαν
MIP-1α, MCP-1, and Desensitization in Anaphylaxis from Cow’s Milk
N Engl J Med 2012; 367:282-284July 19, 2012
To the Editor:
Monocyte chemotactic protein 1 (MCP-1), also known as chemokine (C-C motif) ligand 2, has chemotactic activity for monocytes and basophils and causes the degranulation of basophils and mast cells.1 Another chemokine, macrophage inflammatory protein 1α (MIP-1α), also called chemokine (C-C motif) ligand 3, is produced by macrophages, dendritic cells, and lymphocytes.2 We have observed that 12 children with an allergy to cow’s milk protein,3 the most prevalent food allergy in children, have significantly lower levels of MCP-1 (mean, 11.1 pg per milliliter) and MIP-1α (12.1 pg per milliliter) than children with atopy who do not have this allergy (MCP-1, 28.4 pg per milliliter; and MIP-1α, 29.8 pg per milliliter).
Before desensitization was performed, oral and written informed consent was obtained from all patients or from their parent or guardian. Compilation of the data was recorded in accordance with European standards of data protection, and the study was approved by the clinical research ethics committee of the Hospital Universitario N.S. Candelaria. The study protocol is available with the full text of this letter at NEJM.org.
Twelve children (10 boys and 2 girls) who were 2 to 15 years of age (median, 6 years) with persistent allergy to cow’s milk protein, severe recurrent episodes of grade 2 or 3 anaphylaxis, and multiple visits to the emergency department after accidental ingestion of cow’s milk protein despite an appropriate restrictive diet underwent a 2-day rapid protocol of desensitization in the pediatric critical care unit of Hospital Universitario N.S. Candelaria. All patients had positive skin-prick tests and specific IgE antibodies to cow’s milk protein (mean serum level of specific IgE to cow’s milk protein, >100 kU per liter; mean serum level of specific IgE to casein protein, >100 kU per liter).
Thereafter, a second phase was scheduled in the outpatient clinic for the children to receive increasing doses of undiluted milk for a 6-week period. The goal was for the children to be able to consume 250 ml every 12 hours after this 6-week period. In less than 10 weeks, all 12 children were able to consume 250 ml of milk.
After 2 years, all the children still consumed a glass of milk every day, and their MCP-1 and MIP-1α levels measured by means of flow cytometry (Figure 1A and 1C) were significantly higher than those in children with persistent allergy to cow’s milk protein (P<0.05 by the Mann–Whitney U test). However, there were no significant changes in serum levels of serum cytokines such as interleukins 2, 4, 5, 6, 8, 10, 13, and 17; interferon-γ; eotaxin; RANTES (regulated upon activation normal T-cell expressed and secreted); and tumor necrosis factor α.
Although allergy to cow’s milk protein resolves in 70% of affected children by 3 years of age, its presence still leads to some deaths, life-threatening anaphylaxis, and many concerns in parents and guardians. With the therapeutic intervention described here, children with suspected allergy to cow’s milk protein and anaphylaxis appeared to have less stress4 and to be able to enjoy an unrestricted diet.
Elevated levels of MCP-1 and MIP-1α could reflect an ongoing subclinical response to food substances and to mast-cell degranulation and differential inflammatory-cell recruitment in response to the antigen-specific continuous challenge. We speculate that measurements of levels of MCP-12 and MIP-1α5 might be useful as markers of a successful protocol for milk protein desensitization.
Paloma Poza-R. Glez, M.D., Ph.D.
Hospital del Tórax, Tenerife, Spain
Yvelise Barrios-A. Franco, M.D.
Hospital Universitario de Canarias, Tenerife, Spain
Hospital Universitario N.S. Candelaria, Tenerife, Spain
Supported by the Unidad de Gestión Alergología-Norte, Hospital del Tórax; and by the Foundation of the Spanish Society of Allergology and Clinical Immunology.