[Alpha-Gal-associated delayed red meat anaphylaxis as an occupational disease]. / Alpha-Gal-assoziierte verzögerte Anaphylaxie gegen rotes Fleisch als Berufskrankheit.

In a 30-year-old chef with recurrent delayed angioedema history as well as the experimental detection of IgE antibodies against galactose-alpha-(1,3)-galactose (alpha-Gal) pointed to alpha-Gal as the causative agent. The diagnosis, therefore, was delayed anaphylaxis due to alpha-Gal. Because of the potential relationship to his profession, we submitted a dermatologist's report BK 5101 to the liability and insurance association, whereupon his contract of employment was terminated without notice. As a consequence, we reported an occupational disease. This case demonstrates an underdiagnosed, potentially life-threatening allergy to the disaccharide alpha-Gal in red meat as an occupational disease.

Meat allergy associated with galactosyl-α-(1,3)-galactose (α-Gal)-Closing diagnostic gaps by anti-α-Gal IgE immune profiling.

BACKGROUND: Glycoproteins and glycolipids of some mammalian species contain the disaccharide galactosyl-α-(1,3)-galactose (α-Gal). It is known that α-Gal is immunogenic in humans and causes glycan-specific IgG and also IgE responses with clinical relevance. α-Gal is part of the IgE-reactive monoclonal therapeutic antibody cetuximab (CTX) and is associated with delayed anaphylaxis to red meat. In this study, different α-Gal-containing analytes are examined in singleplex and multiplex assays to resolve individual sensitization patterns with IgE against α-Gal. METHODS: Three serum groups, α-Gal-associated meat allergy (MA) patients, idiopathic anaphylaxis (IA) patients with suspected MA, and non-meat-allergic healthy control individuals (HC), were analyzed via singleplex allergy diagnostics and a newly established immunoblot diagnostic system. The new dot blot detection system resolved individual IgE sensitization profiles for α-Gal-containing analytes CTX, bovine thyroglobulin (Bos d TG), and human serum albumin (HSA)-conjugated α-Gal. RESULTS: Singleplex allergy diagnostics using the α-Gal analytes CTX and Bos d TG confirms the history of MA patients in 91% and 88% of the cases, respectively. A novel dot blot-based assay system for the detection of IgE against α-Gal reveals individual IgE sensitization profiles for α-Gal-containing analytes. An α-Gal-associated IgE cross-reactivity profile (IgE against CTX, Bos d TG, and HSA-α-Gal) was identified, which is associated with MA. CONCLUSIONS: Detection of individual sensitization patterns with different α-Gal-containing analytes provides the basis for an individual allergy diagnosis for α-Gal-sensitized patients. Higher amounts of α-Gal in pork and beef innards compared to muscle meat as indicated by a higher staining intensity are a plausible explanation for the difference in allergic symptom severity.

Association of allelic losses on human chromosomal arms 11Q and 16Q in sporadic breast cancer.

Breast-carcinoma development presumably results from multiple mutational events in tumor-associated genes. Certain results indicate that some tumor-suppressor genes may combine their pathogenetic potential to synergistically promote tumor growth. In an effort to identify such mechanisms in breast tumors, a series of 77 (group I) paired blood tumor samples from patients with sporadic mammary carcinomas was analyzed for loss of heterozygosity with 15 polymorphic markers on the chromosomal arms 7q, 11q, 13q, 16q, 17p and 17q. A significant association was observed for the combination of allelic losses on chromosomes 11q and 16q. In order to confirm these findings, we studied a second independent series of 189 breast-tumor patients (group 2) with comparable histopathological tumor stages. Group 2 was examined for the same genetic alterations using the identical set of polymorphic markers. The data from this group confirmed the detected association of loss of heterozygosity on chromosomes 11q and 16q and indicate the cooperation of putative tumor-suppressor genes on the chromosomal arms 11q and 16q in a sub-set of breast carcinomas. The regions involved harbor the candidate genes ATM (mutated in ataxiatelangiectasia) on chromosome 11q23 and UVO (uvomorulin, cadherin E) and BBCI (breast basic conserved I) on chromosome 16q22-q24.

[Detection of genetic alterations in sporadic breast tumors]. / Nachweis genetischer Alterationen in sporadischen Brusttumoren.

OBJECTIVE: Loss of heterozygosity (LOH) indicates the existence of tumor suppressor genes (TSG) in the affected chromosomal loci. In order to uncover the involvement of such genes, we analyzed LOH in different chromosomal regions of sporadic breast carcinomas. MATERIAL AND METHOD: 47 breast cancer patients were screened for LOH with microsatellite markers on 18 different loci. DNA fragments were amplified by PCR from tumor and reference tissue. The PCR products were run on 8% denaturing polyacrylamide gels and visualized by silver straining. RESULTS: The following LOH-rates were found for the different loci: D6S497 (6p21, WAF-Region): 0%, D7S495: 9%, D7S522: 13%, D7S523: 22%, D11S488 (11q24-25): 38%, D13s321 and D13s765 (13q13-14, Rb-Region): 30% and 17%, D13S260 and D13S267 (13q12.3, BRCA2-Region): 28% both, D16S539 (16q22-24, E-Cadherin-Region): 35%, D17S5 (17p13.3): 17%, TP53 (17p13.1): 32% D17S250 (17q11-12): 22%, D17S855 (17q21 within the BRCA1 gene): 25%, D17S579 (17q21 telomer from BRCA1): 13%, D17S846 (centromere from BRCA1): 17%, 17q24 (SSTR 2): 9%, D22S684 (22q12, NF2-Region): 20%. Overall 66% of the tumors exhibited LOH. Lymphnode positive tumors showed significantly higher LOH rates than lymphnode negative tumors. CONCLUSIONS: Highest LOH-rates were found on chromosomes 11, 13, 16 and 17 indicative of relevant TSG's in the examined loci. In addition the findings indicate prognostic relevance of multiple LOH's in breast cancer.