New Perspectives in the Fight Against Autoimmunity

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New Perspectives in the Fight Against Autoimmunity

Monday August 23, 10:52 am ET

- Roche Researchers Discover That a Naturally Occurring Peptide Influences

Immune Response -

BASEL, Switzerland and NUTLEY, N.J., Aug. 23 /PRNewswire/ -- The September

issue of Nature Immunology reports that researchers at Roche Basel in

collaboration with immunologists at the Harvard Medical School, Boston, MA,

have discovered a naturally occurring peptide that could play a pivotal role

in the fight against autoimmune diseases. The so called CLIP (class II

associated invariant chain peptide) peptide lowers the production of those

cells of the immune system that are critical in triggering pro-inflammatory

immune responses, including autoimmunity. This finding may give rise to new

therapeutic strategies in particular in the field of rheumatoid arthritis

(RA).

" RA belongs to the group of autoimmune diseases that depend on the expansion

of a subset of blood cells -- so called helper T lymphocytes (TH1) " ,

explained Harald Kropshofer, Ph.D., Roche Head Non-clinical Immunology.

" Particular TH1 cells contribute to autoimmunity by recognizing proteins of

our own body, thereby triggering adverse reactions of the immune system

against the body's own tissues. At a certain stage, these TH1 cells begin to

secrete hormone-like substances, such as interferon-gamma (IFN-gamma),

interleukin-2 (IL-2) or interleukin-6 (IL-6), that can trigger, mediate and

maintain autoimmune diseases. Hence, a peptide that helps to lower the

generation rate or abundance of these TH1 cells could be an extremely

helpful approach in RA therapy. "

Kropshofer's team, along with one led by Anne Vogt, Ph.D., Head Applied

Immunology, Roche Center for Medical Genomics, showed in a series of

preclinical studies that specialized cells of the immune system, termed

'dendritic cells', turn on the natural occurring peptide CLIP on the cell

surface which reduces the number of helper T cells changing to the TH1 type.

Thus, CLIP appeared to function as a novel type of peptide regulator. More

important, the researchers found that synthetic CLIP had the same function

as naturally occurring CLIP. This opens up the possibility of using

synthetic CLIP or variants thereof as therapeutic agents. CLIP mediates its

activity by binding to molecules of the major histocompatibility complex

(MHC) class II which are being viewed as risk factors for RA and other

autoimmune diseases.

" The potential pharmacological importance of this discovery comes from the

fact that modulating levels of CLIP may be used to modulate the immune

response itself, " said Ira Mellman, Department Head Ludwig Institute of

Cancer Research, Yale University, New Haven.

About Autoimmune Diseases

Autoimmune diseases are a number of disorders, most of them serious,

resulting from an inappropriate or excessive response by components of the

immune system. The cause is a breakdown in the mechanisms controlling

immunological tolerance to the body's own tissues. As a result, antibodies

or certain T lymphocytes attack the body's own proteins or healthy cells.

For Roche's immunologists, findings from basic research are the cornerstone

of the quest for novel, highly specific medicines aimed as closely as

possible at the root causes of autoimmune diseases and rejection reactions

following organ transplantation.

A long list of clinical entities is recognized as autoimmune diseases,

including multiple sclerosis, certain types of diabetes, and rheumatoid

arthritis. Based on the need for more effective treatments, Roche is

currently investigating seven compounds in early stage clinical development

for autoimmune diseases as well as RA.

Rheumatoid Arthritis (RA)

Rheumatoid arthritis (RA) is a progressive, systemic autoimmune disease

characterized by inflammation of the membrane lining in joints. This

inflammation causes a loss of joint shape and alignment, resulting in pain,

stiffness and swelling, ultimately leading to irreversible joint destruction

and disability. Characteristics of RA include redness, swelling, pain, and

movement limitation around joints of the hands, feet, elbows, knees and

neck. In more severe cases of RA the eyes, lungs or blood vessels may be

involved. RA may also shorten life expectancy by affecting major organ

systems. RA is one of the most common forms of autoimmune disease and

affects more than 6 million people worldwide.