The relationship between ehrlichiosis and the development of hematologic malignancies.

Viral and bacterial infections cause chronic inflammation and produce bacterial metabolites that may lead to carcinogenesis. Ehrlichiosis is an intracellular infection that primarily infects white blood cells. Given that infections can lead to cancer, and that Ehrlichia has tropism for white blood cells, it can be deduced that Ehrlichia may cause hematologic malignancies, such as acute leukemia. A prospective study was performed that tested the blood of ten patients with acute leukemia for prior exposure to Ehrlichia. The RT-PCR that was performed did not detect Ehrlichia DNA in any of the ten samples. Therefore, based on this small study, one cannot conclude that Ehrlichia can lead to hematologic malignancies.

Could ehrlichial infection cause some of the changes associated with leukemia, myelodysplastic diseases and autoimmune disorders, and offer antibiotic treatment options?

We hypothesize that a large group of medical conditions of unknown etiology including leukemia, multiple myeloma, myelodysplastic and autoimmune disorders, may be associated with or caused by an obscure group of intracellular obligate parasitic bacteria named Ehrlichia/Anaplasma (EA). Ensconced in the stem cells of the bone marrow, EA may disrupt the normal development and function of many of the cells of immunity, manifesting itself as different syndromes. Recent studies of the activity of EA suggest direct effects on the immune system consistent with the manifestations of leukemia. We reference here three leukemia patients with direct or indirect evidence of EA infection. Moreover, EA have been shown to be most sensitive to rifamycins. Two moribund leukemia patients with levels of platelets and white cells incompatible with life were treated with therapeutic doses of Rifampin. Though they did not survive, their condition improved dramatically for a time, suggesting Rifampin provided some therapeutic benefit. We assert that these results warrant more extensive study.

Diabetic retinopathy and ehrlichia: the possible relationship.

In the United States, 20,000 patients each year lose their sight from diabetic retinopathy. The cause has been attributed to a failure of control of glucose levels. Recent studies have challenged this, and have suggested that there is no evidence for a consistent glycemic threshold in various populations relating to the incidence of retinopathy. The Ehrlichia have been recently suggested as having a role in diabetes. The action of this obligate parasitic bacterium which often affects the cells involved in immunity has the potential of affecting various tissues randomly. This includes self-reactive T or B cells which may be erroneously altered or released from the marrow because of infection of marrow precursors by an Ehrlichia. The discovery of a gene obtained by molecular methodology from a leukemia patient, has given us a tool to identify by molecular methods, the presence of this gene and assumed bacterium in the blood of patients with various syndromes that includes diabetes. Because of the inconsistent evidence of a uniform glycemic threshold in retinopathy and the failure of its control, this hypothesis raises the question of something else that might be causing this damage. The suspected bacterium in diabetes may have as a significant side effect of its infection of the immune system, specifically the site of action of damage to the small vessels of the retina which could lead to what is regularly described in retinopathy; further, and that may include damage to other vessels seen in peripheral and coronary arteries. The availability of a molecular test in whole blood specimens from diabetics suggests a survey for the gene of the bacterium described in diabetic patients and matched controls. Such an investigation could lead to other therapies directed against the bacterium's presence in the marrow if discovered, and strategies to eliminate the harmful self-reactive T or B cells, if found in diabetes.

Ehrlichia and bone marrow cells: could Ehrlichial infection explain the unsuspected etiology of some diseases of the immune system?

A large group of diseases of unknown etiology, including leukemia, systemic lupus erythematosus, myelodysplastic disease, multiple sclerosis, amyotrophic lateral sclerosis, and rheumatoid arthritis, all present with some elements of immune system disturbance. The Ehrlichia/anaplasma (EA) are an obscure group of obligate parasitic intracellular pathogens that excrete intracellularly a substance called host transcriptional protein, which can alter transcription in cell division. Infection with EA may lead to changes in transcription in proliferating cells, such as those in the marrow, and alter the biology of the products such as T and B cells. Normally 60% of B cells produced in the marrow may be self reactive, but are eliminated before release from the marrow. Changes in transcription could allow self reactive cells to escape into the peripheral circulation and injure normal tissue, creating the dysfunctions which characterize the different immune system diseases and give them their separate identities. A number of studies previously published, and new information presented here, suggest that EA infections may be an underlying, undiagnosed cause for these and other immune system diseases. This hypothesis, long overlooked, has never been subjected to adequate, rigorous study sufficient to prove or disprove its truth. If so, patients may be treated with antibiotics, and marrow transplant manipulations already used in treatment of diseases such as lupus and leukemia may become more effective.