Methods and compositions for use in the diagnosis and treatment of chronic immune disease

Abstract

Methods and compositions are provided for use in the diagnosis and treatment of a host suffering from a chronic immune disease. In the diagnostic methods of the subject invention, a host derived sample, typically PBMC or a derivative thereof, is assayed for the presence of low molecular weight fragments of RNase L, typically in conjunction with an evaluation of caspase activity. The results of this assay are then employed to diagnose and/or characterize a chronic immune disease in the host. In the treatment methods of the subject invention, an effective amount of agent capable of enhancing RNase L homodimer activity in the host, e.g., in host PBMC, is administered to the host. Also provided are methods for identifying agents having RNase L cleavage-inhibitory activity or RNase L fragment antagonist activity.

Description

TECHNICAL FIELD The field of this invention is chronic immune disease, particularly chronic fatigue syndrome and multiple sclerosis. BACKGROUND OF THE INVENTION Chronic immune diseases can be highly debilitating. Two such chronic immune diseases are multiple sclerosis and chronic fatigue syndrome. Multiple sclerosis (MS) is a neurological illness of unknown etiology associated with attacks of focal or multi-focal neurological dysfunction arising from lesions within the central nervous system (CNS). In America and Northern Europe, MS is the most common neurological disease, with prevalence rates estimated between 50-100 per 100,000 population. The onset of disease is most common in early adulthood. Recurrent attacks can occur over many years, with approximately 30 percent of the patients progressing to a severe form of the disease which can be fatal. MS is pleomorphic in its presentation. The clinical manifestations are determined in part by the location of the foci of demyelinat...

AI Technical Summary

Benefits of technology

Methods and compositions are provided for use in the diagnosis and treatment of a host suffering from a chronic immune disease. In the diagnostic methods of the subject invention, a host derived sample, typically PBMC or a derivative thereof, is assayed for the presence of low molecular weight fragments of RNase L, typically in conjunction with an evaluation of caspase activity. The results of this assay are then employed to diagnose and / or characterize a chronic immune disease in the host. In the treatment methods of the subject invention, an effective amount of agent capable of enhancing RNase L homodimer activity in the host, e.g., in host PBMC, is administered to the host. Also provided are methods for identifying agents having RNase L cleavage-inhibitory activity, i.e, agents that inhibit the cleavage of RNase L, or RNase L fragment antagonist activity.

Problems solved by technology

Chronic immune diseases can be highly debilitating.

The characterization of MS disease activity (including diagnosis, determination of disease state, monitoring of disease progression, prediction of disease attacks, and the like), remains problematic.

Examination of the brain for demyelinating plaques, using magnetic resonance imaging (MRI) is useful but expensive, and is not warranted except in a small group of patients in which all other clinical and laboratory tests are negative.

Furthermore, there is no diagnostic laboratory test to determine if a patient is having an attack, to monitor the progress of the attack, to determine if the patient is progressing to a more active form of the disease (i.e., progressive / relapsing), etc.

Finally, there is no laboratory test available as a prognostic indicator and / or capable of monitoring the course of therapy.

As the above discussion demonstrates, currently employed methods of diagnosing and / or characterizing MS or CFS disease activity in a subject are inadequate.

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