elevated serum levels of eosinophil-derived neurotoxin and major basic protein), and increased expression of a marker for T cell activation, interleukin-2 receptor alpha chain, are absent in individuals with familial eosinophilia but common in other types of hypereosinophilia. Accompanying diseases
In spite of being generally considered a benign expression of eosinophilia, isolated cases of family members with familial eosinophilia have been afflicted with tissue dysfunctions that are often associated with more pathological forms of eosinophilia. These dysfunctions include fatal endomyocardial fibrosis, valvular heart disease, and diminished motor and/or sensory function in skin areas served by peripheral nerves. Three patients with heart tissue for pathology examination had eosinophilic infiltration or fibrosis in their hearts endomyocardium. One patient who died suddenly had autopsy findings of eosinophilic infiltration not only in the heart but also in lungs, gastrointestinal tract, and meninges. It is unclear whether these tissue damages were due to primary eosinophil infiltrations or eosinophil infiltrations secondary to other causes. Genetics
Familial eosinophilia is an autosomal dominant disorder. Genetic linkage gene mapping family studies localize the gene responsible for this disease to chromosome 5 at position q31-q33, between markers D5S642 and D5S816. Studies on other disorders associated with high levels of blood eosinophils (e.g. childhood asthma, schistosomiasis) have likewise linked eosinophilia to the q31-q33 area of chromosome 5. The 5q31-q33 region contains a cytokine gene cluster that includes genes for Interleukin 3, interleukin 5, and granulocyte-macrophage colony-stimulating factor. Each of these genes functions to promote the proliferation and differentiation of eosinophil precursor cells.
Nonetheless, no gene polymorphisms were found within the promoters, exons, or introns of these 3 genes or in the regions IL-3/GM-CSF enhancer. In addition to these studies, 8 affected members of a family with familial eosinophilia had peripheral blood or bone marrow cells that carried the same chromosome abnormality, a pericentric inversion of chromosome 10, inv (10) (p11.2q21.2). The meaning and relationship, if any, of this inversion to familial eosinophilia is unclear. Pathophysiology
Earlier studies found no evidence of abnormal blood levels of interleukin 5, interleukin 3, or granulocyte-macrophage colony stimulating factor. A more recent study used a more sensitive assay for interleukin 5 to compare members of a single extended family with some members lacking the disorder. The study found that members with the disorder had: a) peripheral blood mononuclear cells as well as T helper cells (major physiological source of interleukin 5), CD8+ cells, CD14+ cells, and CD19+ cells that expressed high levels of messenger RNA for interleukin 5 while their peripheral blood mononuclear cells expressed normal levels of messenger RNA for RAD50, a gene in close proximity to IL-5; b) elevated serum levels of interleukin 5 as well as soluble Interleukin 5 receptor alpha subunit; and c) innate lymphoid cells (also major physiological sources of interleukin 5) that produced increased amounts of interleukin 5 in response to stimulation. A second family with asymptomatic eosinophilia over three generations likewise exhibited increased production of interleukin 5.